WEBVTT

NOTE duration: "00:58:36.842"


NOTE Confidence: 0.8850818

00:00:00.719 --> 00:00:02.340
I'm doctor Miriam Lustberg,

NOTE Confidence: 0.9997171

00:00:02.800 --> 00:00:05.040
and I'm joined today by

NOTE Confidence: 0.9997171

00:00:05.040 --> 00:00:06.019
two colleagues

NOTE Confidence: 0.8763021

00:00:06.799 --> 00:00:08.660
from the Yale Breast Program,

NOTE Confidence: 0.880227

00:00:09.679 --> 00:00:11.380
doctor Sarah Shellhorn

NOTE Confidence: 0.98242563

00:00:11.759 --> 00:00:13.620
and doctor Dan O'Neil.

NOTE Confidence: 0.90262234

00:00:14.434 --> 00:00:16.134
We are all breast oncologists,

NOTE Confidence: 0.9651961

00:00:16.914 --> 00:00:18.695
and we will be focusing

NOTE Confidence: 0.9651961

00:00:18.835 --> 00:00:19.574
on today

NOTE Confidence: 0.9963398

00:00:20.435 --> 00:00:22.695
on all aspects of metastatic

NOTE Confidence: 0.9963398

00:00:22.835 --> 00:00:23.654
breast cancer,

NOTE Confidence: 0.985556

00:00:24.275 --> 00:00:25.974
in terms of systemic therapies,

NOTE Confidence: 0.9745982

00:00:27.395 --> 00:00:28.755
what are we currently using

NOTE Confidence: 0.9745982

00:00:28.755 --> 00:00:29.920
in the clinic as well

NOTE Confidence: 0.9745982

00:00:29.920 --> 00:00:31.860
as clinical trials as well

NOTE Confidence: 0.9745982

00:00:32.080 --> 00:00:33.140
as some of the,

NOTE Confidence: 0.9673085

00:00:33.760 --> 00:00:34.820
newer emerging,

NOTE Confidence: 0.98438454

00:00:35.440 --> 00:00:35.940
therapies.

NOTE Confidence: 0.9935039

00:00:36.640 --> 00:00:37.920
There will be ample time

NOTE Confidence: 0.9935039

00:00:37.920 --> 00:00:38.659
for questions.

NOTE Confidence: 0.9995395

00:00:39.040 --> 00:00:40.239
So as you think of

NOTE Confidence: 0.9995395

00:00:40.239 --> 00:00:42.020
questions, feel free to

NOTE Confidence: 0.98092616

00:00:42.479 --> 00:00:43.520
put them in the in

NOTE Confidence: 0.98092616

00:00:43.520 --> 00:00:45.140
the q and a portion,

NOTE Confidence: 0.97671366

00:00:45.935 --> 00:00:46.835
of the portal,

NOTE Confidence: 0.9771824

00:00:47.455 --> 00:00:48.575
and we should have,

NOTE Confidence: 0.9992738

00:00:49.534 --> 00:00:50.975
time to to get to

NOTE Confidence: 0.9992738

00:00:50.975 --> 00:00:52.354
to most of your questions.

NOTE Confidence: 0.95994216

00:00:53.695 --> 00:00:54.195
So,

NOTE Confidence: 0.9823984

00:00:55.135 --> 00:00:56.755
so so the focus tonight,

NOTE Confidence: 0.99253356

00:00:57.535 --> 00:00:58.735
is is, as I mentioned,

NOTE Confidence: 0.99253356

00:00:58.735 --> 00:01:00.275
on metastatic breast cancer,

NOTE Confidence: 0.9923646

00:01:01.190 --> 00:01:02.250
where the primary,

NOTE Confidence: 0.99880314

00:01:03.590 --> 00:01:05.270
most effective therapy is a

NOTE Confidence: 0.99880314

00:01:05.270 --> 00:01:07.209
systemic therapy. So we'll be

NOTE Confidence: 0.99880314

00:01:07.270 --> 00:01:08.950
talking about the different subtypes

NOTE Confidence: 0.99880314

00:01:08.950 --> 00:01:09.930
of breast cancer

NOTE Confidence: 0.9846942

00:01:10.470 --> 00:01:10.790
and,

NOTE Confidence: 0.9998726

00:01:11.270 --> 00:01:12.170
what the different

NOTE Confidence: 0.99984735

00:01:12.550 --> 00:01:14.415
management strategies are.

NOTE Confidence: 0.97388166

00:01:14.975 --> 00:01:16.575
With that, I will turn

NOTE Confidence: 0.97388166

00:01:16.575 --> 00:01:18.255
it over to doctor Sarah

NOTE Confidence: 0.97388166

00:01:18.255 --> 00:01:18.755
Schallhorn.

NOTE Confidence: 0.9905155

00:01:20.575 --> 00:01:22.575
Thank you, Mariam, and welcome

NOTE Confidence: 0.9905155

00:01:22.575 --> 00:01:24.655
to everybody. I'm delighted to

NOTE Confidence: 0.9905155

00:01:24.655 --> 00:01:26.430
be here tonight. I just

NOTE Confidence: 0.9905155

00:01:26.430 --> 00:01:27.630
took a quick peek over

NOTE Confidence: 0.9905155

00:01:27.630 --> 00:01:29.310
at the attendee list, and

NOTE Confidence: 0.9905155

00:01:29.310 --> 00:01:30.850
I see some familiar faces.

NOTE Confidence: 0.9905155

00:01:30.910 --> 00:01:31.950
So for those of you

NOTE Confidence: 0.9905155

00:01:31.950 --> 00:01:33.069
I know, welcome. And for

NOTE Confidence: 0.9905155

00:01:33.069 --> 00:01:34.190
those of you that I

NOTE Confidence: 0.9905155

00:01:34.190 --> 00:01:34.930
don't know,

NOTE Confidence: 0.99726605

00:01:35.310 --> 00:01:35.810
welcome.

NOTE Confidence: 0.9524189

00:01:37.390 --> 00:01:37.709
But,

NOTE Confidence: 0.9924408

00:01:38.270 --> 00:01:39.709
doctor O'Neil and I have

NOTE Confidence: 0.9924408

00:01:39.709 --> 00:01:41.635
divided up our time. We

NOTE Confidence: 0.9924408

00:01:41.635 --> 00:01:42.854
were asked to prepare

NOTE Confidence: 0.999529

00:01:43.635 --> 00:01:45.815
ten to fifteen minutes of

NOTE Confidence: 0.999529

00:01:45.875 --> 00:01:47.895
of information about metastatic

NOTE Confidence: 0.9814503

00:01:48.275 --> 00:01:49.635
breast cancer. And so we

NOTE Confidence: 0.9814503

00:01:49.635 --> 00:01:51.795
divided that in into two

NOTE Confidence: 0.9814503

00:01:51.795 --> 00:01:53.415
groups, and I'll be discussing

NOTE Confidence: 0.9814503

00:01:53.475 --> 00:01:53.975
primarily

NOTE Confidence: 0.99277985

00:01:54.650 --> 00:01:56.270
two subtypes of breast cancer,

NOTE Confidence: 0.9815912

00:01:56.570 --> 00:01:58.729
HER2 positive and triple negative

NOTE Confidence: 0.9815912

00:01:58.729 --> 00:02:00.110
metastatic breast cancer.

NOTE Confidence: 0.9334363

00:02:00.570 --> 00:02:01.850
And doctor O'Neil will be

NOTE Confidence: 0.9334363

00:02:01.850 --> 00:02:02.990
taking on the

NOTE Confidence: 0.9680579

00:02:03.530 --> 00:02:05.130
the huge topic of hormone

NOTE Confidence: 0.9680579

00:02:05.130 --> 00:02:06.830
receptor positive breast cancer.

NOTE Confidence: 0.75491494

00:02:08.145 --> 00:02:08.645
And

NOTE Confidence: 0.98441535

00:02:09.025 --> 00:02:10.485
this is easily

NOTE Confidence: 0.989149

00:02:11.345 --> 00:02:13.285
this this topic could easily

NOTE Confidence: 0.989149

00:02:13.345 --> 00:02:14.965
take up several hours.

NOTE Confidence: 0.99244744

00:02:15.905 --> 00:02:17.264
We could we could wax

NOTE Confidence: 0.99244744

00:02:17.264 --> 00:02:18.625
poetic for a really long

NOTE Confidence: 0.99244744

00:02:18.625 --> 00:02:19.125
time.

NOTE Confidence: 0.98612994

00:02:19.825 --> 00:02:21.750
So trying to condense this

NOTE Confidence: 0.98612994

00:02:21.830 --> 00:02:23.430
to just ten to fifteen

NOTE Confidence: 0.98612994

00:02:23.430 --> 00:02:24.730
minutes was a challenge.

NOTE Confidence: 0.9930811

00:02:25.750 --> 00:02:26.710
But we we will give

NOTE Confidence: 0.9930811

00:02:26.710 --> 00:02:27.450
it a try.

NOTE Confidence: 0.9929495

00:02:28.389 --> 00:02:30.550
So very, very quickly, what

NOTE Confidence: 0.9929495

00:02:30.550 --> 00:02:32.330
is metastatic breast cancer?

NOTE Confidence: 0.9936725

00:02:33.270 --> 00:02:34.870
As many of you likely

NOTE Confidence: 0.9936725

00:02:34.870 --> 00:02:37.145
know, it's cancer that started

NOTE Confidence: 0.9936725

00:02:37.145 --> 00:02:38.125
in the breasts.

NOTE Confidence: 0.9953169

00:02:38.425 --> 00:02:40.105
And and when cancer starts

NOTE Confidence: 0.9953169

00:02:40.105 --> 00:02:41.625
in the breasts, it starts

NOTE Confidence: 0.9953169

00:02:41.625 --> 00:02:42.365
to develop

NOTE Confidence: 0.9979636

00:02:42.825 --> 00:02:44.205
two basic characteristics

NOTE Confidence: 0.95995027

00:02:44.585 --> 00:02:46.205
that make cancer cancer.

NOTE Confidence: 0.98721886

00:02:46.905 --> 00:02:47.725
One of them

NOTE Confidence: 0.93926895

00:02:48.025 --> 00:02:49.645
is the ability to grow

NOTE Confidence: 0.93926895

00:02:49.705 --> 00:02:50.580
without any

NOTE Confidence: 0.21578492

00:03:02.500 --> 00:03:02.595
a

NOTE Confidence: 0.84442985

00:03:05.555 --> 00:03:06.855
start to form cancer,

NOTE Confidence: 0.9948109

00:03:08.195 --> 00:03:10.115
that stays within the breast

NOTE Confidence: 0.9948109

00:03:10.115 --> 00:03:11.635
and stays within the lobes

NOTE Confidence: 0.9948109

00:03:11.635 --> 00:03:12.675
or the ducts of the

NOTE Confidence: 0.9948109

00:03:12.675 --> 00:03:13.175
breast.

NOTE Confidence: 0.98963016

00:03:13.955 --> 00:03:15.095
Then they can become

NOTE Confidence: 0.99947315

00:03:15.395 --> 00:03:15.895
invasive

NOTE Confidence: 0.99597883

00:03:16.514 --> 00:03:17.255
and develop

NOTE Confidence: 0.99601924

00:03:17.790 --> 00:03:20.350
into metastatic disease. When those

NOTE Confidence: 0.99601924

00:03:20.350 --> 00:03:22.510
cancer cells invade, they break

NOTE Confidence: 0.99601924

00:03:22.510 --> 00:03:23.870
through the lining of the

NOTE Confidence: 0.99601924

00:03:23.870 --> 00:03:25.570
duct or the lobe,

NOTE Confidence: 0.99851495

00:03:26.830 --> 00:03:28.910
and start to invade into

NOTE Confidence: 0.99851495

00:03:28.910 --> 00:03:30.669
either the bloodstream or the

NOTE Confidence: 0.99851495

00:03:30.669 --> 00:03:31.169
lymphatics

NOTE Confidence: 0.98967755

00:03:32.015 --> 00:03:33.535
and travel to other parts

NOTE Confidence: 0.98967755

00:03:33.535 --> 00:03:34.275
of the body.

NOTE Confidence: 0.99071276

00:03:34.655 --> 00:03:36.435
So the definition of metastatic

NOTE Confidence: 0.99071276

00:03:36.575 --> 00:03:38.035
breast cancer is

NOTE Confidence: 0.9937221

00:03:38.495 --> 00:03:40.255
breast cancer cells that have

NOTE Confidence: 0.9937221

00:03:40.255 --> 00:03:41.855
traveled to another part of

NOTE Confidence: 0.9937221

00:03:41.855 --> 00:03:42.975
the body. And the most

NOTE Confidence: 0.9937221

00:03:42.975 --> 00:03:44.735
common places for breast cancer

NOTE Confidence: 0.9937221

00:03:44.735 --> 00:03:46.670
to go are the lung,

NOTE Confidence: 0.9937221

00:03:46.810 --> 00:03:48.750
the liver, and the bones

NOTE Confidence: 0.82920843

00:03:49.209 --> 00:03:50.190
with a fourth

NOTE Confidence: 0.999105

00:03:50.730 --> 00:03:51.950
most common location

NOTE Confidence: 0.99851626

00:03:52.410 --> 00:03:53.550
being the brain.

NOTE Confidence: 0.9997528

00:03:55.450 --> 00:03:56.910
And when we think about

NOTE Confidence: 0.9997528

00:03:56.970 --> 00:03:59.209
how metastatic breast cancer is

NOTE Confidence: 0.9997528

00:03:59.209 --> 00:03:59.709
treated,

NOTE Confidence: 0.99947286

00:04:00.644 --> 00:04:02.344
we first look at

NOTE Confidence: 0.99916816

00:04:02.644 --> 00:04:04.644
three different proteins. We look

NOTE Confidence: 0.99916816

00:04:04.644 --> 00:04:06.885
at the estrogen receptor, the

NOTE Confidence: 0.99916816

00:04:06.885 --> 00:04:07.385
progesterone

NOTE Confidence: 0.97687584

00:04:07.685 --> 00:04:09.765
receptor, and a protein called

NOTE Confidence: 0.97687584

00:04:09.765 --> 00:04:10.265
HER2,

NOTE Confidence: 0.9993245

00:04:11.364 --> 00:04:13.064
on every breast cancer

NOTE Confidence: 0.9925034

00:04:13.364 --> 00:04:15.144
specimen. So the pathologist

NOTE Confidence: 0.9903877

00:04:15.444 --> 00:04:17.470
looks at a biopsy specimen,

NOTE Confidence: 0.9903877

00:04:17.690 --> 00:04:19.130
looks at these cells under

NOTE Confidence: 0.9903877

00:04:19.130 --> 00:04:20.970
the microscope, and measures the

NOTE Confidence: 0.9903877

00:04:20.970 --> 00:04:21.470
amount

NOTE Confidence: 0.9709232

00:04:21.850 --> 00:04:23.710
of estrogen receptor and progesterone

NOTE Confidence: 0.9709232

00:04:23.850 --> 00:04:25.770
receptor and then a protein

NOTE Confidence: 0.9709232

00:04:25.770 --> 00:04:26.810
called HER2. We'll talk about

NOTE Confidence: 0.9709232

00:04:26.810 --> 00:04:27.710
it in a second.

NOTE Confidence: 0.93555117

00:04:28.089 --> 00:04:28.589
And,

NOTE Confidence: 0.98574173

00:04:30.135 --> 00:04:31.095
I'm I'm gonna leave a

NOTE Confidence: 0.98574173

00:04:31.095 --> 00:04:32.295
little of this for doctor

NOTE Confidence: 0.98574173

00:04:32.295 --> 00:04:34.235
O'Neil, but estrogen and progesterone

NOTE Confidence: 0.98574173

00:04:34.455 --> 00:04:35.595
are female hormones

NOTE Confidence: 0.92407405

00:04:36.214 --> 00:04:37.195
that even

NOTE Confidence: 0.98987997

00:04:37.654 --> 00:04:39.654
after menopause are circulating in

NOTE Confidence: 0.98987997

00:04:39.654 --> 00:04:41.335
in some level in the

NOTE Confidence: 0.98987997

00:04:41.335 --> 00:04:41.835
bloodstream.

NOTE Confidence: 0.99936074

00:04:42.370 --> 00:04:43.650
And the presence of the

NOTE Confidence: 0.99936074

00:04:43.650 --> 00:04:45.410
estrogen receptor and presence of

NOTE Confidence: 0.99936074

00:04:45.410 --> 00:04:46.069
the progesterone

NOTE Confidence: 0.9996146

00:04:46.370 --> 00:04:48.229
receptor on a cancer cell

NOTE Confidence: 0.9952709

00:04:48.529 --> 00:04:49.029
means

NOTE Confidence: 0.9974757

00:04:49.569 --> 00:04:51.410
that that cancer cell is

NOTE Confidence: 0.9974757

00:04:51.410 --> 00:04:51.910
fueled

NOTE Confidence: 0.87286234

00:04:52.370 --> 00:04:53.830
at least in part

NOTE Confidence: 0.99843496

00:04:54.395 --> 00:04:56.255
by those hormones. So cancers

NOTE Confidence: 0.99843496

00:04:56.475 --> 00:04:58.154
that have the estrogen and

NOTE Confidence: 0.99843496

00:04:58.154 --> 00:05:00.235
or progesterone receptor are hormone

NOTE Confidence: 0.99843496

00:05:00.235 --> 00:05:01.214
receptor positive

NOTE Confidence: 0.99389803

00:05:01.755 --> 00:05:04.015
and tend to respond to

NOTE Confidence: 0.908144

00:05:04.635 --> 00:05:06.635
anti hormone types of treatment.

NOTE Confidence: 0.908144

00:05:06.635 --> 00:05:07.915
So that's the sub the

NOTE Confidence: 0.908144

00:05:07.915 --> 00:05:09.375
subject of doctor O'Neil's

NOTE Confidence: 0.9974597

00:05:09.950 --> 00:05:11.470
whole spiel, which we'll get

NOTE Confidence: 0.9974597

00:05:11.470 --> 00:05:12.450
to in a second.

NOTE Confidence: 0.95280266

00:05:13.710 --> 00:05:15.470
The the third protein that

NOTE Confidence: 0.95280266

00:05:15.470 --> 00:05:16.910
we look for is a

NOTE Confidence: 0.95280266

00:05:16.910 --> 00:05:18.529
protein called HER2.

NOTE Confidence: 0.9994904

00:05:19.310 --> 00:05:21.710
And HER2 is a protein

NOTE Confidence: 0.9994904

00:05:21.710 --> 00:05:23.089
that sits on the surface

NOTE Confidence: 0.9347761

00:05:23.390 --> 00:05:24.690
of cancer cells,

NOTE Confidence: 0.99918896

00:05:25.255 --> 00:05:25.755
and

NOTE Confidence: 0.97632444

00:05:26.295 --> 00:05:27.915
it's there in low numbers

NOTE Confidence: 0.97632444

00:05:27.975 --> 00:05:29.815
normally, but sometimes it can

NOTE Confidence: 0.97632444

00:05:29.815 --> 00:05:30.955
be present in

NOTE Confidence: 0.9793472

00:05:31.495 --> 00:05:32.555
in higher levels.

NOTE Confidence: 0.99750733

00:05:33.815 --> 00:05:35.415
And when it's present in

NOTE Confidence: 0.99750733

00:05:35.415 --> 00:05:36.775
higher levels, that can be

NOTE Confidence: 0.99750733

00:05:36.775 --> 00:05:39.115
the driving force for cancer.

NOTE Confidence: 0.98702747

00:05:39.449 --> 00:05:40.669
So lots of HER2

NOTE Confidence: 0.99898857

00:05:41.130 --> 00:05:42.970
can make those cancer cells

NOTE Confidence: 0.99898857

00:05:42.970 --> 00:05:44.110
want to grow faster,

NOTE Confidence: 0.99978495

00:05:44.810 --> 00:05:46.029
and spread quicker.

NOTE Confidence: 0.954371

00:05:48.810 --> 00:05:49.710
And so,

NOTE Confidence: 0.9969908

00:05:53.205 --> 00:05:55.284
the topic of my portion

NOTE Confidence: 0.9969908

00:05:55.284 --> 00:05:57.064
of this program is is

NOTE Confidence: 0.9681474

00:05:57.365 --> 00:05:59.544
HER2 positive breast cancers

NOTE Confidence: 0.96094227

00:06:00.164 --> 00:06:01.865
and then another subtype

NOTE Confidence: 0.915902

00:06:02.724 --> 00:06:04.876
called triple negative breast cancer.

NOTE Confidence: 0.915902

00:06:04.876 --> 00:06:06.610
And so we talked about

NOTE Confidence: 0.915902

00:06:06.610 --> 00:06:08.050
the three different receptors that

NOTE Confidence: 0.915902

00:06:08.050 --> 00:06:09.889
we check, the estrogen receptor,

NOTE Confidence: 0.915902

00:06:09.889 --> 00:06:11.570
the progesterone receptor, and then

NOTE Confidence: 0.915902

00:06:11.570 --> 00:06:13.669
this protein called HER2. And

NOTE Confidence: 0.915902

00:06:13.730 --> 00:06:15.089
when the cancer cells do

NOTE Confidence: 0.915902

00:06:15.089 --> 00:06:16.785
not have any of those

NOTE Confidence: 0.915902

00:06:16.865 --> 00:06:18.785
three proteins, that's one, two,

NOTE Confidence: 0.915902

00:06:18.785 --> 00:06:20.565
three proteins that are negative,

NOTE Confidence: 0.915902

00:06:20.865 --> 00:06:21.904
it's where we get the

NOTE Confidence: 0.915902

00:06:21.904 --> 00:06:23.585
title or the name triple

NOTE Confidence: 0.915902

00:06:23.585 --> 00:06:24.805
negative breast cancer.

NOTE Confidence: 0.99804324

00:06:25.825 --> 00:06:26.945
So I'm gonna first start

NOTE Confidence: 0.99804324

00:06:26.945 --> 00:06:28.645
with triple negative breast cancer.

NOTE Confidence: 0.981201

00:06:30.949 --> 00:06:32.389
These aren't cancers that are

NOTE Confidence: 0.981201

00:06:32.389 --> 00:06:33.210
fueled by

NOTE Confidence: 0.8947417

00:06:33.589 --> 00:06:35.370
hormones. They are not

NOTE Confidence: 0.9906065

00:06:35.830 --> 00:06:38.150
fueled by having extra amounts

NOTE Confidence: 0.9906065

00:06:38.150 --> 00:06:38.889
of HER2.

NOTE Confidence: 0.8906531

00:06:39.350 --> 00:06:40.089
And, unfortunately,

NOTE Confidence: 0.9981499

00:06:40.949 --> 00:06:42.490
that means that the mainstay

NOTE Confidence: 0.9981499

00:06:42.550 --> 00:06:43.210
of treatment

NOTE Confidence: 0.9996828

00:06:43.795 --> 00:06:44.615
is chemotherapy

NOTE Confidence: 0.9678563

00:06:44.995 --> 00:06:45.495
drugs.

NOTE Confidence: 0.9740266

00:06:45.955 --> 00:06:47.475
And these are chemotherapy drugs

NOTE Confidence: 0.9740266

00:06:47.475 --> 00:06:49.714
that are generally given through,

NOTE Confidence: 0.9740266

00:06:50.035 --> 00:06:51.235
through the vein in an

NOTE Confidence: 0.9740266

00:06:51.235 --> 00:06:52.455
intravenous fashion.

NOTE Confidence: 0.9997506

00:06:52.835 --> 00:06:54.915
And these drugs go everywhere

NOTE Confidence: 0.9997506

00:06:54.915 --> 00:06:55.735
in the body

NOTE Confidence: 0.9885354

00:06:56.115 --> 00:06:57.870
with the idea of trying

NOTE Confidence: 0.9885354

00:06:57.949 --> 00:07:00.130
to kill cancer cells wherever

NOTE Confidence: 0.9885354

00:07:00.190 --> 00:07:01.630
they might be. And we

NOTE Confidence: 0.9885354

00:07:01.630 --> 00:07:02.750
have lots and lots of

NOTE Confidence: 0.9885354

00:07:02.750 --> 00:07:04.910
chemo drugs that work in

NOTE Confidence: 0.9885354

00:07:04.910 --> 00:07:06.190
breast cancer and in in

NOTE Confidence: 0.9885354

00:07:06.190 --> 00:07:07.729
triple negative breast cancer,

NOTE Confidence: 0.9817544

00:07:09.630 --> 00:07:10.910
but they have lots of

NOTE Confidence: 0.9817544

00:07:10.910 --> 00:07:12.110
side effects. This is one

NOTE Confidence: 0.9817544

00:07:12.110 --> 00:07:13.275
of the big problems with

NOTE Confidence: 0.9817544

00:07:13.435 --> 00:07:15.435
chemotherapy. It can affect almost

NOTE Confidence: 0.9817544

00:07:15.435 --> 00:07:16.875
every organ system in the

NOTE Confidence: 0.9817544

00:07:16.875 --> 00:07:18.715
body from the brain all

NOTE Confidence: 0.9817544

00:07:18.715 --> 00:07:19.854
the way to the muscles,

NOTE Confidence: 0.9784038

00:07:20.395 --> 00:07:21.995
from the lungs to the

NOTE Confidence: 0.9784038

00:07:21.995 --> 00:07:22.495
genitourinary

NOTE Confidence: 0.98502207

00:07:23.115 --> 00:07:23.615
system.

NOTE Confidence: 0.99639165

00:07:24.315 --> 00:07:25.755
Any part of the body

NOTE Confidence: 0.99639165

00:07:25.755 --> 00:07:27.115
can be affected by by

NOTE Confidence: 0.99639165

00:07:27.115 --> 00:07:27.615
chemotherapy

NOTE Confidence: 0.96838874

00:07:27.995 --> 00:07:30.090
because it's not particularly specific.

NOTE Confidence: 0.99101007

00:07:30.630 --> 00:07:31.530
It doesn't

NOTE Confidence: 0.9994668

00:07:31.910 --> 00:07:32.970
target anything.

NOTE Confidence: 0.96748734

00:07:33.670 --> 00:07:36.330
It really affects any cell

NOTE Confidence: 0.96748734

00:07:36.390 --> 00:07:37.210
that's growing,

NOTE Confidence: 0.9770526

00:07:37.590 --> 00:07:38.870
and that can be normal

NOTE Confidence: 0.9770526

00:07:38.870 --> 00:07:40.150
cells like the lining of

NOTE Confidence: 0.9770526

00:07:40.150 --> 00:07:40.810
the gut,

NOTE Confidence: 0.9690398

00:07:41.190 --> 00:07:42.710
normal cells like they're in

NOTE Confidence: 0.9690398

00:07:42.710 --> 00:07:43.370
the skin,

NOTE Confidence: 0.972544

00:07:44.685 --> 00:07:45.905
normal cells anywhere.

NOTE Confidence: 0.8795341

00:07:48.445 --> 00:07:51.005
Furthermore, chemotherapy has even more

NOTE Confidence: 0.8795341

00:07:51.005 --> 00:07:52.305
downsides. It's inconvenient.

NOTE Confidence: 0.9879052

00:07:52.845 --> 00:07:54.685
It requires frequent visits to

NOTE Confidence: 0.9879052

00:07:54.685 --> 00:07:56.065
clinic and to infusion.

NOTE Confidence: 0.99772143

00:07:56.765 --> 00:07:58.600
This can impact things,

NOTE Confidence: 0.9814912

00:07:59.139 --> 00:08:01.139
that are really important in

NOTE Confidence: 0.9814912

00:08:01.139 --> 00:08:02.760
a woman's life, like

NOTE Confidence: 0.94911605

00:08:03.139 --> 00:08:04.980
child care, trying to arrange

NOTE Confidence: 0.94911605

00:08:04.980 --> 00:08:05.480
transportation.

NOTE Confidence: 0.9959293

00:08:07.380 --> 00:08:09.000
These drugs are generally intravenous,

NOTE Confidence: 0.9959293

00:08:09.139 --> 00:08:10.360
which means that that

NOTE Confidence: 0.98554873

00:08:10.905 --> 00:08:12.825
getting an IV over time

NOTE Confidence: 0.98554873

00:08:12.825 --> 00:08:13.785
can be more and more

NOTE Confidence: 0.98554873

00:08:13.785 --> 00:08:15.725
challenging. Because every time you

NOTE Confidence: 0.98554873

00:08:15.785 --> 00:08:16.825
put an IV in, you

NOTE Confidence: 0.98554873

00:08:16.825 --> 00:08:17.625
create a little bit of

NOTE Confidence: 0.98554873

00:08:17.625 --> 00:08:18.445
scar tissue.

NOTE Confidence: 0.98969054

00:08:20.185 --> 00:08:21.225
It can lead to loss

NOTE Confidence: 0.98969054

00:08:21.225 --> 00:08:22.825
of work productivity, which can

NOTE Confidence: 0.98969054

00:08:22.825 --> 00:08:24.365
cause what we call financial

NOTE Confidence: 0.98969054

00:08:24.425 --> 00:08:26.849
toxicity or financial harm to

NOTE Confidence: 0.98969054

00:08:26.849 --> 00:08:27.729
people who have to deal

NOTE Confidence: 0.98969054

00:08:27.729 --> 00:08:29.250
with chemotherapy over the long

NOTE Confidence: 0.98969054

00:08:29.250 --> 00:08:30.530
term. And it can have

NOTE Confidence: 0.98969054

00:08:30.530 --> 00:08:31.889
tremendous effects on on a

NOTE Confidence: 0.98969054

00:08:31.889 --> 00:08:33.269
woman's mental health.

NOTE Confidence: 0.9853264

00:08:34.130 --> 00:08:35.570
In fact, this is work

NOTE Confidence: 0.9853264

00:08:35.570 --> 00:08:36.610
that I did a number

NOTE Confidence: 0.9853264

00:08:36.610 --> 00:08:37.510
of years ago.

NOTE Confidence: 0.99667776

00:08:38.610 --> 00:08:40.595
Not just physical concerns,

NOTE Confidence: 0.99065423

00:08:41.375 --> 00:08:42.355
impact people,

NOTE Confidence: 0.9998171

00:08:42.895 --> 00:08:43.395
getting

NOTE Confidence: 0.9790656

00:08:43.855 --> 00:08:45.615
getting chemotherapy. And when we

NOTE Confidence: 0.9790656

00:08:45.615 --> 00:08:46.815
showed that almost half of

NOTE Confidence: 0.9790656

00:08:46.815 --> 00:08:48.015
patients or over half of

NOTE Confidence: 0.9790656

00:08:48.015 --> 00:08:50.015
patients have more concerns with

NOTE Confidence: 0.9790656

00:08:50.015 --> 00:08:51.395
things that aren't physical.

NOTE Confidence: 0.97953844

00:08:54.920 --> 00:08:56.520
So I apologize if this

NOTE Confidence: 0.97953844

00:08:56.520 --> 00:08:57.800
feels a little bit choppy

NOTE Confidence: 0.97953844

00:08:57.800 --> 00:08:59.000
because it is. There's just

NOTE Confidence: 0.97953844

00:08:59.000 --> 00:09:00.380
a lot to say here.

NOTE Confidence: 0.998785

00:09:01.000 --> 00:09:02.540
Some of the most exciting,

NOTE Confidence: 0.9998156

00:09:04.200 --> 00:09:06.059
drugs that we're using now

NOTE Confidence: 0.9929066

00:09:06.434 --> 00:09:07.875
belong to a class of

NOTE Confidence: 0.9929066

00:09:07.875 --> 00:09:10.615
medicines called antibody drug conjugates.

NOTE Confidence: 0.9929066

00:09:10.675 --> 00:09:11.635
So we talked a little

NOTE Confidence: 0.9929066

00:09:11.635 --> 00:09:12.995
bit about the fact that

NOTE Confidence: 0.9929066

00:09:12.995 --> 00:09:13.495
chemotherapy

NOTE Confidence: 0.84243006

00:09:14.355 --> 00:09:14.855
is,

NOTE Confidence: 0.80362535

00:09:17.075 --> 00:09:17.735
it targets

NOTE Confidence: 0.99337465

00:09:18.530 --> 00:09:20.050
all different types of cells

NOTE Confidence: 0.99337465

00:09:20.050 --> 00:09:21.590
regardless of where they are.

NOTE Confidence: 0.99337465

00:09:21.730 --> 00:09:23.590
But antibody drug conjugates,

NOTE Confidence: 0.9786182

00:09:24.050 --> 00:09:24.929
I'd like to think of

NOTE Confidence: 0.9786182

00:09:24.929 --> 00:09:26.690
them more like tumor seeking

NOTE Confidence: 0.9786182

00:09:26.690 --> 00:09:27.190
missiles.

NOTE Confidence: 0.99054915

00:09:27.730 --> 00:09:28.610
So there's been a lot

NOTE Confidence: 0.99054915

00:09:28.610 --> 00:09:29.970
of talk about antibodies over

NOTE Confidence: 0.99054915

00:09:29.970 --> 00:09:31.184
the last five years since

NOTE Confidence: 0.99054915

00:09:31.184 --> 00:09:32.065
the the start of the

NOTE Confidence: 0.99054915

00:09:32.065 --> 00:09:34.084
COVID pandemic, but antibodies

NOTE Confidence: 0.99945277

00:09:36.304 --> 00:09:36.884
are proteins

NOTE Confidence: 0.9998498

00:09:37.264 --> 00:09:38.404
created by

NOTE Confidence: 0.99783564

00:09:38.785 --> 00:09:40.005
by lymphocytes

NOTE Confidence: 0.96305174

00:09:40.464 --> 00:09:41.985
in part of the immune

NOTE Confidence: 0.96305174

00:09:41.985 --> 00:09:42.485
system.

NOTE Confidence: 0.99972546

00:09:43.410 --> 00:09:44.629
But we can create

NOTE Confidence: 0.9838429

00:09:45.009 --> 00:09:46.529
antibodies in the lab. These

NOTE Confidence: 0.9838429

00:09:46.529 --> 00:09:48.290
are called monoclonal antibodies, and

NOTE Confidence: 0.9838429

00:09:48.290 --> 00:09:50.209
they they basically are like

NOTE Confidence: 0.9838429

00:09:50.209 --> 00:09:52.050
targets for particular proteins. So

NOTE Confidence: 0.9838429

00:09:52.050 --> 00:09:53.170
you have an antibody to

NOTE Confidence: 0.9838429

00:09:53.170 --> 00:09:53.829
a particular

NOTE Confidence: 0.9968835

00:09:54.209 --> 00:09:54.709
protein.

NOTE Confidence: 0.9859513

00:09:55.490 --> 00:09:56.790
And so

NOTE Confidence: 0.9969626

00:09:58.105 --> 00:09:59.865
what an antibody drug conjugate

NOTE Confidence: 0.9969626

00:09:59.865 --> 00:10:00.365
is

NOTE Confidence: 0.9466831

00:10:00.825 --> 00:10:02.925
is an antibody that's targeting

NOTE Confidence: 0.9466831

00:10:02.985 --> 00:10:03.645
a protein

NOTE Confidence: 0.9500915

00:10:04.105 --> 00:10:06.184
on the cancer cell. And

NOTE Confidence: 0.9500915

00:10:06.184 --> 00:10:08.125
riding along with it, attached

NOTE Confidence: 0.9500915

00:10:08.345 --> 00:10:09.245
to the antibody,

NOTE Confidence: 0.9966736

00:10:09.865 --> 00:10:11.910
is a chemotherapy drug. We

NOTE Confidence: 0.9966736

00:10:11.910 --> 00:10:12.970
call that the payload.

NOTE Confidence: 0.97888917

00:10:13.509 --> 00:10:15.110
The chemotherapy drug is riding

NOTE Confidence: 0.97888917

00:10:15.110 --> 00:10:16.389
along with the antibody. So

NOTE Confidence: 0.97888917

00:10:16.389 --> 00:10:18.149
the antibody finds the tumor.

NOTE Confidence: 0.97888917

00:10:18.149 --> 00:10:19.589
It finds the protein that

NOTE Confidence: 0.97888917

00:10:19.589 --> 00:10:20.949
it's looking for. It binds

NOTE Confidence: 0.97888917

00:10:20.949 --> 00:10:22.149
to that protein, and it

NOTE Confidence: 0.97888917

00:10:22.149 --> 00:10:22.649
delivers

NOTE Confidence: 0.99896955

00:10:23.509 --> 00:10:24.170
the chemotherapy

NOTE Confidence: 0.9903355

00:10:24.629 --> 00:10:26.605
directly to the tumor. And

NOTE Confidence: 0.9903355

00:10:26.605 --> 00:10:27.825
there are a few different

NOTE Confidence: 0.9903355

00:10:27.885 --> 00:10:29.565
antibody drug conjugates that have

NOTE Confidence: 0.9903355

00:10:29.565 --> 00:10:31.405
come come about over the

NOTE Confidence: 0.9903355

00:10:31.405 --> 00:10:33.085
last five, ten years, and

NOTE Confidence: 0.9903355

00:10:33.085 --> 00:10:34.145
we'll talk about

NOTE Confidence: 0.99949217

00:10:34.525 --> 00:10:35.825
most of them here.

NOTE Confidence: 0.99883157

00:10:37.405 --> 00:10:39.345
The second class of medicines

NOTE Confidence: 0.99883157

00:10:39.485 --> 00:10:40.845
that's used in triple negative

NOTE Confidence: 0.99883157

00:10:40.845 --> 00:10:41.665
breast cancer

NOTE Confidence: 0.9806013

00:10:42.580 --> 00:10:43.160
is immunotherapy.

NOTE Confidence: 0.9540447

00:10:44.100 --> 00:10:44.839
And immunotherapy,

NOTE Confidence: 0.99978095

00:10:46.660 --> 00:10:47.160
targets

NOTE Confidence: 0.99929845

00:10:47.779 --> 00:10:48.279
the

NOTE Confidence: 0.9325867

00:10:48.660 --> 00:10:50.200
immune system. And more

NOTE Confidence: 0.99147666

00:10:51.059 --> 00:10:52.820
appropriately, it actually takes the

NOTE Confidence: 0.99147666

00:10:52.820 --> 00:10:54.675
brakes off the immune system.

NOTE Confidence: 0.99147666

00:10:54.675 --> 00:10:56.275
So in the presence of

NOTE Confidence: 0.99147666

00:10:56.275 --> 00:10:56.775
cancer,

NOTE Confidence: 0.99536926

00:10:57.635 --> 00:10:59.155
the immune system kinda says,

NOTE Confidence: 0.99536926

00:10:59.155 --> 00:11:00.515
well, that that looks a

NOTE Confidence: 0.99536926

00:11:00.515 --> 00:11:01.554
little bit like me. It

NOTE Confidence: 0.99536926

00:11:01.554 --> 00:11:02.915
looks a little bit like

NOTE Confidence: 0.99536926

00:11:02.915 --> 00:11:03.415
self.

NOTE Confidence: 0.9966321

00:11:03.795 --> 00:11:05.015
I'm gonna back off.

NOTE Confidence: 0.98658323

00:11:05.875 --> 00:11:07.075
So the cancer cell kind

NOTE Confidence: 0.98658323

00:11:07.075 --> 00:11:07.575
of

NOTE Confidence: 0.98891187

00:11:07.929 --> 00:11:09.290
puts the brakes on the

NOTE Confidence: 0.98891187

00:11:09.290 --> 00:11:10.730
immune system, not allowing the

NOTE Confidence: 0.98891187

00:11:10.730 --> 00:11:11.929
immune system to fight the

NOTE Confidence: 0.98891187

00:11:11.929 --> 00:11:12.429
cancer.

NOTE Confidence: 0.99955547

00:11:12.970 --> 00:11:13.950
But immunotherapies

NOTE Confidence: 0.83112365

00:11:14.890 --> 00:11:15.790
like Keytruda,

NOTE Confidence: 0.9947158

00:11:17.050 --> 00:11:18.090
probably the one we use

NOTE Confidence: 0.9947158

00:11:18.090 --> 00:11:19.610
most commonly in breast cancer,

NOTE Confidence: 0.9947158

00:11:19.610 --> 00:11:21.050
but there are others used

NOTE Confidence: 0.9947158

00:11:21.050 --> 00:11:22.350
in other types of cancers,

NOTE Confidence: 0.97175264

00:11:23.605 --> 00:11:25.205
works to take the brakes

NOTE Confidence: 0.97175264

00:11:25.205 --> 00:11:26.885
off the immune system. So

NOTE Confidence: 0.97175264

00:11:26.885 --> 00:11:27.545
it allows,

NOTE Confidence: 0.9889102

00:11:28.725 --> 00:11:30.505
a person's a patient's body,

NOTE Confidence: 0.96786594

00:11:30.965 --> 00:11:32.565
a patient's own immune system

NOTE Confidence: 0.96786594

00:11:32.565 --> 00:11:33.945
to help fight the cancer.

NOTE Confidence: 0.9723293

00:11:34.405 --> 00:11:36.259
And that reactivates the immune

NOTE Confidence: 0.9723293

00:11:36.259 --> 00:11:38.360
system so that in combination

NOTE Confidence: 0.9723293

00:11:38.660 --> 00:11:39.399
with chemotherapy,

NOTE Confidence: 0.99843836

00:11:41.300 --> 00:11:43.379
the the immune system can

NOTE Confidence: 0.99843836

00:11:43.379 --> 00:11:45.220
then fight the cancer and

NOTE Confidence: 0.99843836

00:11:45.220 --> 00:11:47.079
get a more robust response.

NOTE Confidence: 0.99843836

00:11:47.220 --> 00:11:48.120
So immunotherapy

NOTE Confidence: 0.9996506

00:11:48.500 --> 00:11:49.959
is another class of medicines

NOTE Confidence: 0.9996506

00:11:50.019 --> 00:11:51.745
that we use primarily in

NOTE Confidence: 0.9996506

00:11:51.745 --> 00:11:53.205
triple negative breast cancer.

NOTE Confidence: 0.94097155

00:11:54.145 --> 00:11:54.885
And finally,

NOTE Confidence: 0.9991972

00:11:55.825 --> 00:11:58.245
another target that's that's applicable

NOTE Confidence: 0.6471568

00:11:58.785 --> 00:11:59.285
for

NOTE Confidence: 0.9994192

00:11:59.745 --> 00:12:00.245
several

NOTE Confidence: 0.99017674

00:12:01.024 --> 00:12:02.385
types of breast cancer, but

NOTE Confidence: 0.99017674

00:12:02.385 --> 00:12:03.365
those particularly

NOTE Confidence: 0.9935441

00:12:04.420 --> 00:12:06.980
associated with BRCA one and

NOTE Confidence: 0.9935441

00:12:06.980 --> 00:12:07.480
BRCA

NOTE Confidence: 0.9278605

00:12:07.860 --> 00:12:08.679
two mutations.

NOTE Confidence: 0.9690731

00:12:09.940 --> 00:12:11.400
These are called PARP inhibitors.

NOTE Confidence: 0.99941844

00:12:12.100 --> 00:12:13.140
And it has to do

NOTE Confidence: 0.99941844

00:12:13.300 --> 00:12:15.080
PARP inhibitors have to do

NOTE Confidence: 0.99941844

00:12:15.380 --> 00:12:15.880
with

NOTE Confidence: 0.9017873

00:12:16.340 --> 00:12:18.760
normal cell division. And and

NOTE Confidence: 0.9997605

00:12:19.245 --> 00:12:20.845
people who have these types

NOTE Confidence: 0.9997605

00:12:20.845 --> 00:12:21.585
of mutations

NOTE Confidence: 0.9845422

00:12:22.045 --> 00:12:23.325
in in BRCA one and

NOTE Confidence: 0.9845422

00:12:23.325 --> 00:12:24.545
BRCA two,

NOTE Confidence: 0.9989029

00:12:26.205 --> 00:12:27.885
in the normal process of

NOTE Confidence: 0.9989029

00:12:27.885 --> 00:12:28.625
cell division,

NOTE Confidence: 0.9794995

00:12:30.205 --> 00:12:31.184
they make mistakes.

NOTE Confidence: 0.98358876

00:12:31.565 --> 00:12:33.485
They make more mistakes than

NOTE Confidence: 0.98358876

00:12:33.485 --> 00:12:33.985
than

NOTE Confidence: 0.9981047

00:12:34.285 --> 00:12:35.620
is usual. And when those

NOTE Confidence: 0.9981047

00:12:35.620 --> 00:12:37.139
mistakes happen in the normal

NOTE Confidence: 0.9981047

00:12:37.139 --> 00:12:38.440
process of cell division,

NOTE Confidence: 0.9996538

00:12:38.899 --> 00:12:40.519
cancers are much more likely.

NOTE Confidence: 0.97918695

00:12:42.660 --> 00:12:43.720
The the

NOTE Confidence: 0.91675144

00:12:44.740 --> 00:12:45.639
PARP inhibitor,

NOTE Confidence: 0.99552125

00:12:46.980 --> 00:12:48.420
well, actually, people with these

NOTE Confidence: 0.99552125

00:12:48.420 --> 00:12:50.600
mutations aren't able to

NOTE Confidence: 0.96297216

00:12:51.195 --> 00:12:53.115
repair those mistakes in as

NOTE Confidence: 0.96297216

00:12:53.115 --> 00:12:55.195
an efficient way as someone

NOTE Confidence: 0.96297216

00:12:55.195 --> 00:12:56.475
who who doesn't have those

NOTE Confidence: 0.96297216

00:12:56.475 --> 00:12:58.095
mutations. And PARP inhibitors

NOTE Confidence: 0.99098086

00:12:58.875 --> 00:12:59.375
work,

NOTE Confidence: 0.9997939

00:13:00.155 --> 00:13:01.135
by preventing

NOTE Confidence: 0.99800855

00:13:01.515 --> 00:13:02.015
repair

NOTE Confidence: 0.9118537

00:13:02.635 --> 00:13:03.135
and

NOTE Confidence: 0.99685407

00:13:03.540 --> 00:13:05.140
basically lead these cells to

NOTE Confidence: 0.99685407

00:13:05.140 --> 00:13:06.899
commit suicide. So PARP inhibitors

NOTE Confidence: 0.99685407

00:13:06.899 --> 00:13:08.500
are pills that we use

NOTE Confidence: 0.99685407

00:13:08.500 --> 00:13:10.179
fairly frequently in people that

NOTE Confidence: 0.99685407

00:13:10.179 --> 00:13:11.959
have these types of mutations.

NOTE Confidence: 0.9674933

00:13:13.380 --> 00:13:15.640
So moving very quickly to

NOTE Confidence: 0.9674933

00:13:15.860 --> 00:13:17.800
HER2 positive breast cancer.

NOTE Confidence: 0.9775303

00:13:18.335 --> 00:13:20.335
So remember, HER2 is a

NOTE Confidence: 0.9775303

00:13:20.335 --> 00:13:21.615
protein that's on the surface

NOTE Confidence: 0.9775303

00:13:21.615 --> 00:13:22.975
of cancer cells. And when

NOTE Confidence: 0.9775303

00:13:22.975 --> 00:13:24.495
HER2 is there in high

NOTE Confidence: 0.9775303

00:13:24.495 --> 00:13:26.035
levels or it's overexpressed,

NOTE Confidence: 0.9963318

00:13:27.455 --> 00:13:29.295
that leads that's the the

NOTE Confidence: 0.9963318

00:13:29.295 --> 00:13:31.215
primary driver for growth of

NOTE Confidence: 0.9963318

00:13:31.215 --> 00:13:32.355
those cancer cells.

NOTE Confidence: 0.9841762

00:13:33.790 --> 00:13:36.050
And up until maybe twenty

NOTE Confidence: 0.9841762

00:13:36.270 --> 00:13:38.430
five ish years ago, this

NOTE Confidence: 0.9841762

00:13:38.430 --> 00:13:40.530
was really bad because HER2

NOTE Confidence: 0.9841762

00:13:40.590 --> 00:13:41.970
positive breast cancers,

NOTE Confidence: 0.98932767

00:13:43.150 --> 00:13:44.990
were very aggressive. They had

NOTE Confidence: 0.98932767

00:13:44.990 --> 00:13:47.365
high high likelihood of developing

NOTE Confidence: 0.98932767

00:13:47.365 --> 00:13:49.205
into metastatic disease and high

NOTE Confidence: 0.98932767

00:13:49.205 --> 00:13:51.365
likelihoods of going to going

NOTE Confidence: 0.98932767

00:13:51.365 --> 00:13:51.865
to

NOTE Confidence: 0.98079324

00:13:52.245 --> 00:13:53.765
major organs like the liver

NOTE Confidence: 0.98079324

00:13:53.765 --> 00:13:54.665
and the brain.

NOTE Confidence: 0.9914451

00:13:56.085 --> 00:13:58.245
But at again, about two

NOTE Confidence: 0.9914451

00:13:58.245 --> 00:13:59.705
and a half decades ago,

NOTE Confidence: 0.9914451

00:14:00.005 --> 00:14:01.220
the drug trastuzumab

NOTE Confidence: 0.979702

00:14:01.839 --> 00:14:03.600
or Herceptin was developed, and

NOTE Confidence: 0.979702

00:14:03.600 --> 00:14:05.860
it revolutionized the treatment of

NOTE Confidence: 0.979702

00:14:06.160 --> 00:14:08.240
of metastatic breast cancer first

NOTE Confidence: 0.979702

00:14:08.240 --> 00:14:09.679
and and then earlier stage

NOTE Confidence: 0.979702

00:14:09.679 --> 00:14:10.879
breast cancers a little bit

NOTE Confidence: 0.979702

00:14:10.879 --> 00:14:11.379
later.

NOTE Confidence: 0.92381525

00:14:12.720 --> 00:14:13.699
And that began,

NOTE Confidence: 0.93071383

00:14:15.445 --> 00:14:17.385
a long history of targeting

NOTE Confidence: 0.8285243

00:14:17.925 --> 00:14:18.425
HER2,

NOTE Confidence: 0.96617943

00:14:18.804 --> 00:14:19.945
first with trastuzumab

NOTE Confidence: 0.97173905

00:14:21.045 --> 00:14:23.385
and then later with additional

NOTE Confidence: 0.97173905

00:14:23.525 --> 00:14:25.865
antibody drug conjugates, other monoclonal

NOTE Confidence: 0.97173905

00:14:26.085 --> 00:14:27.305
antibodies, and

NOTE Confidence: 0.99769187

00:14:28.080 --> 00:14:30.880
oral medications called tyrosine kinase

NOTE Confidence: 0.99769187

00:14:30.880 --> 00:14:31.380
inhibitors.

NOTE Confidence: 0.9790966

00:14:31.680 --> 00:14:32.900
This is just the history

NOTE Confidence: 0.9790966

00:14:33.120 --> 00:14:35.380
of HER2 positive breast cancer

NOTE Confidence: 0.9709577

00:14:36.080 --> 00:14:38.000
way back to nineteen thirty

NOTE Confidence: 0.9709577

00:14:38.000 --> 00:14:39.280
five, and not a whole

NOTE Confidence: 0.9709577

00:14:39.280 --> 00:14:41.024
lot happened between nineteen thirty

NOTE Confidence: 0.9709577

00:14:41.024 --> 00:14:42.945
five until nineteen until the

NOTE Confidence: 0.9709577

00:14:42.945 --> 00:14:44.625
nineteen nineties. But starting in

NOTE Confidence: 0.9709577

00:14:44.625 --> 00:14:46.245
nineteen ninety eight when trastuzumab

NOTE Confidence: 0.99599236

00:14:46.704 --> 00:14:47.365
came about,

NOTE Confidence: 0.97591764

00:14:47.745 --> 00:14:48.644
there have been

NOTE Confidence: 0.9933864

00:14:49.024 --> 00:14:50.704
many, many drugs that have

NOTE Confidence: 0.9933864

00:14:50.704 --> 00:14:52.885
been approved in various settings.

NOTE Confidence: 0.9194946

00:14:54.100 --> 00:14:55.399
Lapatinib, pertuzumab,

NOTE Confidence: 0.91475934

00:14:55.779 --> 00:14:57.220
a drug called TDM one

NOTE Confidence: 0.91475934

00:14:57.220 --> 00:14:57.959
or Kadcyla,

NOTE Confidence: 0.76528525

00:14:58.579 --> 00:15:00.199
neratinib or new NERLYNX,

NOTE Confidence: 0.7569866

00:15:01.860 --> 00:15:02.360
pirotinib,

NOTE Confidence: 0.95455784

00:15:02.740 --> 00:15:04.600
tucatinib, neratinib, margetuximab,

NOTE Confidence: 0.99654394

00:15:05.379 --> 00:15:06.435
all of these drugs have

NOTE Confidence: 0.99654394

00:15:06.435 --> 00:15:07.875
come about over just the

NOTE Confidence: 0.99654394

00:15:07.875 --> 00:15:09.575
last decade or so,

NOTE Confidence: 0.9962758

00:15:10.435 --> 00:15:10.935
in

NOTE Confidence: 0.9706749

00:15:11.395 --> 00:15:12.995
for patients with HER2 positive

NOTE Confidence: 0.9706749

00:15:12.995 --> 00:15:15.495
breast cancer. So really quickly,

NOTE Confidence: 0.994049

00:15:16.915 --> 00:15:17.735
HER2 positive

NOTE Confidence: 0.9892648

00:15:19.570 --> 00:15:21.810
breast cancer is primarily treated

NOTE Confidence: 0.9892648

00:15:21.810 --> 00:15:23.750
first with HER2 antibodies,

NOTE Confidence: 0.98584425

00:15:24.690 --> 00:15:27.250
primarily trastuzumab and pertuzumab, which

NOTE Confidence: 0.98584425

00:15:27.250 --> 00:15:29.250
target that HER2 receptor. And

NOTE Confidence: 0.98584425

00:15:29.250 --> 00:15:30.930
these can be administered either

NOTE Confidence: 0.98584425

00:15:30.930 --> 00:15:33.110
via infusion or a shot.

NOTE Confidence: 0.96971035

00:15:35.195 --> 00:15:36.635
And they're often used together

NOTE Confidence: 0.96971035

00:15:36.635 --> 00:15:38.015
because they block HER2

NOTE Confidence: 0.88045204

00:15:38.635 --> 00:15:40.335
in in complementary ways.

NOTE Confidence: 0.94830847

00:15:40.795 --> 00:15:42.395
Then there are oral HER2

NOTE Confidence: 0.94830847

00:15:42.395 --> 00:15:43.615
drugs like lapatinib,

NOTE Confidence: 0.98380256

00:15:43.915 --> 00:15:45.135
neratinib, tucatinib.

NOTE Confidence: 0.99347866

00:15:46.235 --> 00:15:47.515
Sometimes I wonder who actually

NOTE Confidence: 0.99347866

00:15:47.515 --> 00:15:49.115
names these medications. There's a

NOTE Confidence: 0.99347866

00:15:49.115 --> 00:15:50.290
lot of vowels there. These

NOTE Confidence: 0.99347866

00:15:50.290 --> 00:15:51.110
are hard to

NOTE Confidence: 0.98915076

00:15:51.410 --> 00:15:51.490
say.

NOTE Confidence: 0.99701816

00:15:53.010 --> 00:15:53.990
But these medications

NOTE Confidence: 0.9982367

00:15:54.770 --> 00:15:56.390
block the intracellular

NOTE Confidence: 0.9921789

00:15:56.770 --> 00:15:58.530
signaling that comes from the

NOTE Confidence: 0.9921789

00:15:58.530 --> 00:15:59.350
HER2 receptor

NOTE Confidence: 0.97132087

00:15:59.650 --> 00:16:01.030
leading to cell growth.

NOTE Confidence: 0.9811444

00:16:01.410 --> 00:16:02.390
And then finally,

NOTE Confidence: 0.9799094

00:16:03.285 --> 00:16:04.505
antibody drug conjugates,

NOTE Confidence: 0.99804014

00:16:04.885 --> 00:16:06.185
the tumor targeting

NOTE Confidence: 0.90503216

00:16:06.964 --> 00:16:07.464
missiles.

NOTE Confidence: 0.9253125

00:16:08.404 --> 00:16:09.865
They have a a place

NOTE Confidence: 0.9253125

00:16:10.084 --> 00:16:10.584
in

NOTE Confidence: 0.9802703

00:16:11.045 --> 00:16:12.565
the treatment of HER2 positive

NOTE Confidence: 0.9802703

00:16:12.565 --> 00:16:14.565
breast cancer too. In fact,

NOTE Confidence: 0.9802703

00:16:14.565 --> 00:16:15.945
the two most common,

NOTE Confidence: 0.9994758

00:16:16.964 --> 00:16:18.425
antibody drug conjugates

NOTE Confidence: 0.98322755

00:16:18.990 --> 00:16:21.310
are HER2 targeting antibody drug

NOTE Confidence: 0.98322755

00:16:21.310 --> 00:16:21.810
conjugates.

NOTE Confidence: 0.9899427

00:16:24.029 --> 00:16:25.089
The the latest

NOTE Confidence: 0.9892639

00:16:25.470 --> 00:16:27.149
antibody drug conjugate to come

NOTE Confidence: 0.9892639

00:16:27.149 --> 00:16:28.430
through the pipeline is a

NOTE Confidence: 0.9892639

00:16:28.430 --> 00:16:29.570
drug called nHER2,

NOTE Confidence: 0.9983041

00:16:30.350 --> 00:16:31.649
which is trastuzumab

NOTE Confidence: 0.9999474

00:16:32.190 --> 00:16:32.690
antibody

NOTE Confidence: 0.99775183

00:16:33.255 --> 00:16:34.075
targeting HER2

NOTE Confidence: 0.58342147

00:16:34.695 --> 00:16:35.195
coupled

NOTE Confidence: 0.99723846

00:16:35.575 --> 00:16:37.835
with a a chemotherapy

NOTE Confidence: 0.7931478

00:16:38.375 --> 00:16:39.275
called Dirextican.

NOTE Confidence: 0.9784379

00:16:41.415 --> 00:16:43.815
Another antibody drug conjugate called

NOTE Confidence: 0.9784379

00:16:43.815 --> 00:16:45.355
Kadcyla or trastuzumab

NOTE Confidence: 0.948071

00:16:46.649 --> 00:16:49.070
tansine is that Herceptin antibody

NOTE Confidence: 0.9882541

00:16:49.770 --> 00:16:50.750
coupled to,

NOTE Confidence: 0.9967227

00:16:51.770 --> 00:16:53.870
a chemotherapy called m tansine.

NOTE Confidence: 0.9989022

00:16:54.649 --> 00:16:55.149
And

NOTE Confidence: 0.9887361

00:16:55.529 --> 00:16:57.770
these two drugs have not

NOTE Confidence: 0.9887361

00:16:57.770 --> 00:16:58.270
only,

NOTE Confidence: 0.9992795

00:16:59.605 --> 00:17:01.145
provided us with two additional

NOTE Confidence: 0.9992795

00:17:01.205 --> 00:17:01.705
treatments

NOTE Confidence: 0.9474634

00:17:05.205 --> 00:17:07.605
data coming out just in

NOTE Confidence: 0.9474634

00:17:07.605 --> 00:17:09.625
June of this year looking

NOTE Confidence: 0.9474634

00:17:09.685 --> 00:17:10.185
at,

NOTE Confidence: 0.7550338

00:17:11.205 --> 00:17:12.425
trastuzumab, daroxetacaner,

NOTE Confidence: 0.9779345

00:17:12.805 --> 00:17:13.465
and HER2

NOTE Confidence: 0.99358076

00:17:14.140 --> 00:17:15.580
in the first line setting

NOTE Confidence: 0.99358076

00:17:15.580 --> 00:17:17.260
for people with metastatic HER2

NOTE Confidence: 0.99358076

00:17:17.260 --> 00:17:18.480
positive breast cancer.

NOTE Confidence: 0.99788

00:17:20.380 --> 00:17:22.859
Occasionally, we we also use

NOTE Confidence: 0.99788

00:17:22.859 --> 00:17:23.359
chemotherapy

NOTE Confidence: 0.9895315

00:17:23.900 --> 00:17:25.520
in HER2 positive disease,

NOTE Confidence: 0.99118185

00:17:26.619 --> 00:17:28.160
combined with trastuzumab.

NOTE Confidence: 0.98534966

00:17:29.855 --> 00:17:31.535
And then for patients that

NOTE Confidence: 0.98534966

00:17:31.535 --> 00:17:33.875
have HER2 positive and also

NOTE Confidence: 0.98534966

00:17:33.935 --> 00:17:36.035
hormone receptor positive breast cancer,

NOTE Confidence: 0.98534966

00:17:36.255 --> 00:17:38.755
we also use endocrine therapy.

NOTE Confidence: 0.9737679

00:17:40.175 --> 00:17:41.455
I'm I know I've already

NOTE Confidence: 0.9737679

00:17:41.455 --> 00:17:42.575
gone over the time that

NOTE Confidence: 0.9737679

00:17:42.575 --> 00:17:43.295
I said that I would

NOTE Confidence: 0.9737679

00:17:43.295 --> 00:17:43.795
take,

NOTE Confidence: 0.8674575

00:17:44.940 --> 00:17:46.720
but I wanna just mention

NOTE Confidence: 0.9257573

00:17:47.980 --> 00:17:49.840
the way that new drugs

NOTE Confidence: 0.98632634

00:17:51.260 --> 00:17:52.859
come up and they get

NOTE Confidence: 0.98632634

00:17:52.859 --> 00:17:54.619
approved by the FDA is

NOTE Confidence: 0.98632634

00:17:54.619 --> 00:17:56.480
through a series of clinical

NOTE Confidence: 0.98632634

00:17:56.540 --> 00:17:57.040
trials.

NOTE Confidence: 0.9995542

00:17:57.580 --> 00:17:59.040
And clinical trials

NOTE Confidence: 0.99420077

00:17:59.775 --> 00:18:01.775
require patients. This is how

NOTE Confidence: 0.99420077

00:18:01.775 --> 00:18:02.595
we determine

NOTE Confidence: 0.9914218

00:18:03.215 --> 00:18:04.655
whether a drug is effective

NOTE Confidence: 0.9914218

00:18:04.655 --> 00:18:05.695
or not, and we look

NOTE Confidence: 0.9914218

00:18:05.695 --> 00:18:07.375
at new combinations of drugs

NOTE Confidence: 0.9914218

00:18:07.375 --> 00:18:08.734
and compare them to to

NOTE Confidence: 0.9914218

00:18:08.734 --> 00:18:10.575
older combinations. It's how we

NOTE Confidence: 0.9914218

00:18:10.575 --> 00:18:11.955
move the field forward.

NOTE Confidence: 0.99965966

00:18:12.660 --> 00:18:13.160
Clinical

NOTE Confidence: 0.9839247

00:18:13.780 --> 00:18:15.300
trials, could also be called

NOTE Confidence: 0.9839247

00:18:15.300 --> 00:18:17.960
clinical studies, studies, research trials,

NOTE Confidence: 0.9839247

00:18:18.260 --> 00:18:18.760
protocols.

NOTE Confidence: 0.99860287

00:18:20.260 --> 00:18:21.640
But a clinical trial

NOTE Confidence: 0.97672534

00:18:22.580 --> 00:18:23.080
is,

NOTE Confidence: 0.99963427

00:18:24.420 --> 00:18:25.480
more than just

NOTE Confidence: 0.9917397

00:18:25.975 --> 00:18:27.254
a lab test or a

NOTE Confidence: 0.9917397

00:18:27.254 --> 00:18:28.615
test on a guinea pig.

NOTE Confidence: 0.9917397

00:18:28.615 --> 00:18:29.115
Clinical

NOTE Confidence: 0.8003987

00:18:29.734 --> 00:18:30.475
clinical trials,

NOTE Confidence: 0.9964311

00:18:31.654 --> 00:18:33.434
afford patients an opportunity

NOTE Confidence: 0.99785084

00:18:34.215 --> 00:18:35.835
to contribute to the field

NOTE Confidence: 0.99785084

00:18:35.975 --> 00:18:38.215
and potentially get highly effective

NOTE Confidence: 0.99785084

00:18:38.215 --> 00:18:40.154
therapy even before it's approved.

NOTE Confidence: 0.98821324

00:18:40.980 --> 00:18:42.020
There are lots of phases

NOTE Confidence: 0.98821324

00:18:42.020 --> 00:18:43.700
of clinical trials starting at

NOTE Confidence: 0.98821324

00:18:43.700 --> 00:18:45.700
the earliest phases where we're

NOTE Confidence: 0.98821324

00:18:45.700 --> 00:18:47.460
we're studying new drugs or

NOTE Confidence: 0.98821324

00:18:47.460 --> 00:18:48.980
new combinations of drugs and

NOTE Confidence: 0.98821324

00:18:48.980 --> 00:18:49.480
looking

NOTE Confidence: 0.9958463

00:18:49.859 --> 00:18:50.679
at at toxicities

NOTE Confidence: 0.9894131

00:18:51.140 --> 00:18:52.755
all the way to phase

NOTE Confidence: 0.9894131

00:18:53.075 --> 00:18:55.075
three clinical trials, which are

NOTE Confidence: 0.9894131

00:18:55.075 --> 00:18:55.734
are usually

NOTE Confidence: 0.9996457

00:18:56.115 --> 00:18:56.615
randomized

NOTE Confidence: 0.9845303

00:18:56.915 --> 00:18:58.435
clinical trials where there are

NOTE Confidence: 0.9845303

00:18:58.435 --> 00:18:59.494
multiple arms,

NOTE Confidence: 0.9827709

00:19:00.595 --> 00:19:01.415
of the trial,

NOTE Confidence: 0.9929209

00:19:02.994 --> 00:19:04.595
and even phase four clinical

NOTE Confidence: 0.9929209

00:19:04.595 --> 00:19:06.135
trials, which which happen

NOTE Confidence: 0.9988249

00:19:06.595 --> 00:19:08.055
after a drug is approved.

NOTE Confidence: 0.93138736

00:19:12.500 --> 00:19:13.799
And the the likelihood

NOTE Confidence: 0.9994915

00:19:14.100 --> 00:19:15.720
that a drug becomes FDA

NOTE Confidence: 0.9994915

00:19:15.779 --> 00:19:16.279
approved

NOTE Confidence: 0.9738704

00:19:16.580 --> 00:19:17.940
go gets lower and lower

NOTE Confidence: 0.9738704

00:19:17.940 --> 00:19:19.140
the the later the phase

NOTE Confidence: 0.9738704

00:19:19.140 --> 00:19:19.960
of the trial.

NOTE Confidence: 0.9492039

00:19:22.325 --> 00:19:23.525
That is all that I

NOTE Confidence: 0.9492039

00:19:23.525 --> 00:19:24.345
had prepared

NOTE Confidence: 0.9658117

00:19:24.645 --> 00:19:26.885
for triple negative breast cancer

NOTE Confidence: 0.9658117

00:19:26.885 --> 00:19:28.585
and HER2 positive disease.

NOTE Confidence: 0.99941224

00:19:29.445 --> 00:19:30.425
But I'd love

NOTE Confidence: 0.9994034

00:19:31.045 --> 00:19:32.345
to turn the

NOTE Confidence: 0.9808548

00:19:32.645 --> 00:19:34.725
proverbial microphone over to Dan

NOTE Confidence: 0.9808548

00:19:34.725 --> 00:19:35.225
O'Neil,

NOTE Confidence: 0.933668

00:19:36.210 --> 00:19:37.809
my colleague who is also

NOTE Confidence: 0.933668

00:19:37.809 --> 00:19:39.830
a practicing breast medical oncologist

NOTE Confidence: 0.933668

00:19:39.970 --> 00:19:40.869
to talk about

NOTE Confidence: 0.98527133

00:19:41.170 --> 00:19:43.490
hormone receptor positive breast cancer.

NOTE Confidence: 0.98527133

00:19:43.490 --> 00:19:44.790
And I will stop sharing

NOTE Confidence: 0.99177986

00:19:45.410 --> 00:19:46.609
and turn it over to

NOTE Confidence: 0.99177986

00:19:46.609 --> 00:19:47.750
you, doctor O'Neil.

NOTE Confidence: 0.99266833

00:19:57.315 --> 00:19:59.255
I'm told I'm muted. Okay.

NOTE Confidence: 0.96950114

00:19:59.875 --> 00:20:00.595
Thank you.

NOTE Confidence: 0.93642944

00:20:00.915 --> 00:20:02.215
Thank you to doctor Schallhorn

NOTE Confidence: 0.93642944

00:20:02.275 --> 00:20:03.635
for for doing the,

NOTE Confidence: 0.99619585

00:20:04.789 --> 00:20:05.990
the impressive work of of

NOTE Confidence: 0.99619585

00:20:05.990 --> 00:20:06.710
laying a lot of the

NOTE Confidence: 0.99619585

00:20:06.710 --> 00:20:07.830
groundwork about,

NOTE Confidence: 0.9961249

00:20:08.230 --> 00:20:10.309
you know, what metastatic breast

NOTE Confidence: 0.9961249

00:20:10.309 --> 00:20:11.669
cancer is and and the

NOTE Confidence: 0.9961249

00:20:11.669 --> 00:20:13.109
different types of metastatic breast

NOTE Confidence: 0.9961249

00:20:13.109 --> 00:20:13.609
cancer.

NOTE Confidence: 0.981493

00:20:14.630 --> 00:20:15.590
I'm gonna be talking about

NOTE Confidence: 0.981493

00:20:15.590 --> 00:20:17.429
hormone receptor positive breast cancer,

NOTE Confidence: 0.9638627

00:20:18.070 --> 00:20:19.394
and, you know, specifically hormone

NOTE Confidence: 0.9638627

00:20:19.394 --> 00:20:21.154
receptor positive HER2 negative breast

NOTE Confidence: 0.9638627

00:20:21.154 --> 00:20:22.274
cancer where we don't have

NOTE Confidence: 0.9638627

00:20:22.274 --> 00:20:24.054
overexpression of that HER2 protein.

NOTE Confidence: 0.9145365

00:20:24.674 --> 00:20:26.195
And just like Doctor. Shellhorn

NOTE Confidence: 0.9145365

00:20:26.195 --> 00:20:26.695
described,

NOTE Confidence: 0.9733058

00:20:27.715 --> 00:20:29.554
hormone receptor positive breast cancer

NOTE Confidence: 0.9733058

00:20:29.554 --> 00:20:31.020
is breast cancer that has

NOTE Confidence: 0.9733058

00:20:31.020 --> 00:20:32.960
expression of that estrogen receptor

NOTE Confidence: 0.9733058

00:20:33.180 --> 00:20:34.960
and or that progesterone receptor

NOTE Confidence: 0.9311711

00:20:35.500 --> 00:20:37.340
and is usually primarily driven

NOTE Confidence: 0.9311711

00:20:37.340 --> 00:20:39.040
by the estrogen and progesterone,

NOTE Confidence: 0.976141

00:20:39.580 --> 00:20:41.520
hormones that, that that women

NOTE Confidence: 0.9636107

00:20:41.820 --> 00:20:43.783
are making, you you know,

NOTE Confidence: 0.9636107

00:20:43.783 --> 00:20:45.381
really over their entire lives,

NOTE Confidence: 0.9636107

00:20:45.701 --> 00:20:47.938
to some amount, and, and

NOTE Confidence: 0.9636107

00:20:47.938 --> 00:20:49.536
that you see circulating in

NOTE Confidence: 0.9636107

00:20:49.536 --> 00:20:51.135
the blood in a in

NOTE Confidence: 0.9636107

00:20:51.135 --> 00:20:53.052
a healthy woman. There have

NOTE Confidence: 0.9636107

00:20:53.052 --> 00:20:54.650
been a lot of updates

NOTE Confidence: 0.9636107

00:20:54.650 --> 00:20:55.770
in this in this space.

NOTE Confidence: 0.9636107

00:20:55.770 --> 00:20:56.890
I gave a similar talk

NOTE Confidence: 0.9636107

00:20:56.890 --> 00:20:57.930
about two years ago, and

NOTE Confidence: 0.9636107

00:20:57.930 --> 00:20:58.730
and when I went back

NOTE Confidence: 0.9636107

00:20:58.730 --> 00:21:00.010
to my slides, for for

NOTE Confidence: 0.9636107

00:21:00.010 --> 00:21:01.210
today's talk, I had to

NOTE Confidence: 0.9636107

00:21:01.210 --> 00:21:02.250
make a lot of updates.

NOTE Confidence: 0.9636107

00:21:02.250 --> 00:21:03.530
So so that's really good

NOTE Confidence: 0.9636107

00:21:03.530 --> 00:21:04.030
news.

NOTE Confidence: 0.9969627

00:21:04.330 --> 00:21:05.930
I'm gonna talk about about

NOTE Confidence: 0.9969627

00:21:05.930 --> 00:21:07.450
a lot of, specific drugs

NOTE Confidence: 0.9969627

00:21:07.450 --> 00:21:08.890
that we're we're using, and

NOTE Confidence: 0.9969627

00:21:08.890 --> 00:21:10.430
and how we sequence those.

NOTE Confidence: 0.93880373

00:21:11.425 --> 00:21:12.705
So, to start out thinking

NOTE Confidence: 0.93880373

00:21:12.705 --> 00:21:14.225
about the first line setting

NOTE Confidence: 0.93880373

00:21:14.225 --> 00:21:15.845
or the initial therapies,

NOTE Confidence: 0.9986723

00:21:16.705 --> 00:21:17.925
that a woman is likely

NOTE Confidence: 0.83442366

00:21:18.305 --> 00:21:20.965
to receive for, a new,

NOTE Confidence: 0.90737915

00:21:21.345 --> 00:21:23.665
or metastatic hormone receptor positive

NOTE Confidence: 0.90737915

00:21:23.665 --> 00:21:24.405
breast cancer,

NOTE Confidence: 0.9954899

00:21:25.220 --> 00:21:26.900
the standard there has remained

NOTE Confidence: 0.9954899

00:21:26.900 --> 00:21:28.100
the same for for some

NOTE Confidence: 0.9954899

00:21:28.100 --> 00:21:28.600
time

NOTE Confidence: 0.9293226

00:21:28.980 --> 00:21:30.980
now. The standard, therapy is

NOTE Confidence: 0.9293226

00:21:30.980 --> 00:21:32.340
a combination of a couple

NOTE Confidence: 0.9293226

00:21:32.340 --> 00:21:34.020
of different, types of drugs.

NOTE Confidence: 0.9566467

00:21:34.580 --> 00:21:36.020
The first type of drugs

NOTE Confidence: 0.9566467

00:21:36.020 --> 00:21:37.244
are are kind of,

NOTE Confidence: 0.99956304

00:21:37.725 --> 00:21:38.225
essential

NOTE Confidence: 0.8847713

00:21:38.845 --> 00:21:40.145
anti estrogen backbones,

NOTE Confidence: 0.9591702

00:21:40.525 --> 00:21:42.925
either aromatase inhibitors usually, which

NOTE Confidence: 0.9591702

00:21:42.925 --> 00:21:44.765
are an oral medication or,

NOTE Confidence: 0.9591702

00:21:45.165 --> 00:21:47.585
a injectable medication called fulvestrant.

NOTE Confidence: 0.98192745

00:21:49.085 --> 00:21:50.525
And those two medications have

NOTE Confidence: 0.98192745

00:21:50.525 --> 00:21:51.405
been around for a long,

NOTE Confidence: 0.98192745

00:21:51.405 --> 00:21:52.145
long time.

NOTE Confidence: 0.98579717

00:21:52.530 --> 00:21:53.970
But, within the last several

NOTE Confidence: 0.98579717

00:21:53.970 --> 00:21:54.470
years,

NOTE Confidence: 0.9430208

00:21:55.010 --> 00:21:56.130
a a newer type of

NOTE Confidence: 0.9430208

00:21:56.130 --> 00:21:57.890
medication, a CDK four six

NOTE Confidence: 0.9430208

00:21:57.890 --> 00:21:59.730
inhibitor has been incorporated into

NOTE Confidence: 0.9430208

00:21:59.730 --> 00:22:00.690
into the treatment,

NOTE Confidence: 0.98349494

00:22:01.090 --> 00:22:03.250
combination as well. So CDK

NOTE Confidence: 0.98349494

00:22:03.250 --> 00:22:04.950
four six inhibitors are drugs

NOTE Confidence: 0.98349494

00:22:05.010 --> 00:22:05.510
that,

NOTE Confidence: 0.9730211

00:22:06.655 --> 00:22:07.795
inhibit a pathway,

NOTE Confidence: 0.9996121

00:22:08.494 --> 00:22:10.175
that is part of the

NOTE Confidence: 0.9996121

00:22:10.175 --> 00:22:10.675
process

NOTE Confidence: 0.8708508

00:22:11.055 --> 00:22:12.355
that stands between,

NOTE Confidence: 0.97461027

00:22:12.895 --> 00:22:14.895
the estrogen receptor and the

NOTE Confidence: 0.97461027

00:22:14.895 --> 00:22:16.335
cell telling the cell to

NOTE Confidence: 0.97461027

00:22:16.335 --> 00:22:16.835
divide,

NOTE Confidence: 0.9977069

00:22:17.135 --> 00:22:18.435
in response to estrogen.

NOTE Confidence: 0.967056

00:22:19.109 --> 00:22:20.390
So these CDK four six

NOTE Confidence: 0.967056

00:22:20.390 --> 00:22:22.070
inhibitors interfere with that with

NOTE Confidence: 0.967056

00:22:22.070 --> 00:22:23.609
that signaling, with that communication,

NOTE Confidence: 0.99045664

00:22:24.470 --> 00:22:25.830
and they help the,

NOTE Confidence: 0.9471135

00:22:26.390 --> 00:22:28.070
endocrine therapies, the anti estrogen

NOTE Confidence: 0.9471135

00:22:28.070 --> 00:22:29.830
therapies work for longer than

NOTE Confidence: 0.9471135

00:22:29.830 --> 00:22:31.030
they would all on their

NOTE Confidence: 0.9471135

00:22:31.030 --> 00:22:31.530
own.

NOTE Confidence: 0.9102059

00:22:32.355 --> 00:22:33.955
There are three different CDK

NOTE Confidence: 0.9102059

00:22:33.955 --> 00:22:35.555
four six inhibitors, that are

NOTE Confidence: 0.9102059

00:22:35.555 --> 00:22:36.994
available on the market. They're

NOTE Confidence: 0.9102059

00:22:36.994 --> 00:22:37.494
palbociclib

NOTE Confidence: 0.82561976

00:22:37.795 --> 00:22:39.095
or Ibrance, bemaciclib

NOTE Confidence: 0.96264184

00:22:39.475 --> 00:22:40.215
or Verzenio,

NOTE Confidence: 0.97710836

00:22:40.835 --> 00:22:41.575
and ribociclib

NOTE Confidence: 0.9181943

00:22:41.955 --> 00:22:42.695
or Kisqali.

NOTE Confidence: 0.9730353

00:22:44.380 --> 00:22:45.500
And in in the clinical

NOTE Confidence: 0.9730353

00:22:45.500 --> 00:22:47.659
trials looking at how long

NOTE Confidence: 0.9730353

00:22:47.659 --> 00:22:48.640
they improved,

NOTE Confidence: 0.994044

00:22:49.100 --> 00:22:50.220
the time that a cancer

NOTE Confidence: 0.994044

00:22:50.220 --> 00:22:51.500
was controlled in that first

NOTE Confidence: 0.994044

00:22:51.500 --> 00:22:52.640
line setting,

NOTE Confidence: 0.9945206

00:22:53.179 --> 00:22:54.619
the the results were pretty

NOTE Confidence: 0.9945206

00:22:54.619 --> 00:22:55.100
similar.

NOTE Confidence: 0.9879622

00:22:55.500 --> 00:22:56.460
The average amount of time

NOTE Confidence: 0.9879622

00:22:56.460 --> 00:22:57.405
that a cancer could be

NOTE Confidence: 0.9879622

00:22:57.405 --> 00:22:58.705
controlled with these,

NOTE Confidence: 0.9994996

00:22:59.244 --> 00:23:00.625
these two drugs together

NOTE Confidence: 0.9776928

00:23:00.925 --> 00:23:02.125
was around two years or

NOTE Confidence: 0.9776928

00:23:02.125 --> 00:23:03.085
a little bit longer than

NOTE Confidence: 0.9776928

00:23:03.085 --> 00:23:04.285
two years, and that was

NOTE Confidence: 0.9776928

00:23:04.285 --> 00:23:05.805
that was consistent across all

NOTE Confidence: 0.9776928

00:23:05.805 --> 00:23:06.545
three drugs.

NOTE Confidence: 0.99264514

00:23:08.045 --> 00:23:09.165
In addition to that, there

NOTE Confidence: 0.99264514

00:23:09.165 --> 00:23:10.230
have been studies that look

NOTE Confidence: 0.99264514

00:23:10.309 --> 00:23:12.070
at how long overall life

NOTE Confidence: 0.99264514

00:23:12.070 --> 00:23:12.570
expectancy,

NOTE Confidence: 0.97204876

00:23:13.109 --> 00:23:14.470
is improved by by using

NOTE Confidence: 0.97204876

00:23:14.470 --> 00:23:16.090
these medications early on.

NOTE Confidence: 0.92564356

00:23:16.470 --> 00:23:17.669
And there there there are

NOTE Confidence: 0.92564356

00:23:17.669 --> 00:23:18.950
maybe some differences that have

NOTE Confidence: 0.92564356

00:23:18.950 --> 00:23:19.429
emerged,

NOTE Confidence: 0.9824541

00:23:19.750 --> 00:23:21.109
in in what we call

NOTE Confidence: 0.9824541

00:23:21.109 --> 00:23:22.630
real world trials or trials

NOTE Confidence: 0.9824541

00:23:22.630 --> 00:23:23.750
looking at patients, you know,

NOTE Confidence: 0.9824541

00:23:23.750 --> 00:23:24.950
actually out in the clinic

NOTE Confidence: 0.9824541

00:23:24.950 --> 00:23:26.010
receiving the drugs.

NOTE Confidence: 0.9153472

00:23:26.445 --> 00:23:27.804
There was suggestion that that

NOTE Confidence: 0.9153472

00:23:27.804 --> 00:23:29.105
all three drugs improved,

NOTE Confidence: 0.9254794

00:23:30.445 --> 00:23:31.265
life expectancy.

NOTE Confidence: 0.9838413

00:23:31.965 --> 00:23:33.325
In the in the kind

NOTE Confidence: 0.9838413

00:23:33.325 --> 00:23:35.345
of well controlled clinical trials,

NOTE Confidence: 0.9845975

00:23:35.804 --> 00:23:36.924
that led to the approval

NOTE Confidence: 0.9845975

00:23:36.924 --> 00:23:38.465
of these drugs, ribociclib

NOTE Confidence: 0.9898492

00:23:38.765 --> 00:23:40.144
was probably the best performing,

NOTE Confidence: 0.93359584

00:23:40.524 --> 00:23:42.340
increasing life expectancy by about

NOTE Confidence: 0.93359584

00:23:42.340 --> 00:23:43.480
it by about a year.

NOTE Confidence: 0.9862892

00:23:46.179 --> 00:23:47.539
So that's the first line

NOTE Confidence: 0.9862892

00:23:47.539 --> 00:23:48.980
setting. That's been stable. A

NOTE Confidence: 0.9862892

00:23:48.980 --> 00:23:50.419
lot of the the newer

NOTE Confidence: 0.9862892

00:23:50.419 --> 00:23:51.799
approaches and newer medications,

NOTE Confidence: 0.9300694

00:23:52.659 --> 00:23:54.020
really start to crop up

NOTE Confidence: 0.9300694

00:23:54.020 --> 00:23:55.940
in the, second line setting

NOTE Confidence: 0.9300694

00:23:55.940 --> 00:23:57.140
in in one situation and

NOTE Confidence: 0.9300694

00:23:57.140 --> 00:23:58.235
first line setting that I'll

NOTE Confidence: 0.9300694

00:23:58.235 --> 00:23:59.055
that I'll describe.

NOTE Confidence: 0.9483386

00:24:00.555 --> 00:24:01.935
When you're looking at,

NOTE Confidence: 0.9863244

00:24:02.555 --> 00:24:03.915
the next therapy, when when

NOTE Confidence: 0.9863244

00:24:03.915 --> 00:24:05.115
the cancer is no longer

NOTE Confidence: 0.9863244

00:24:05.115 --> 00:24:07.115
well, well controlled with those

NOTE Confidence: 0.9863244

00:24:07.115 --> 00:24:08.015
first drugs,

NOTE Confidence: 0.960059

00:24:08.475 --> 00:24:09.995
something that's really important sort

NOTE Confidence: 0.960059

00:24:09.995 --> 00:24:11.515
of thematically is to think

NOTE Confidence: 0.960059

00:24:11.515 --> 00:24:12.495
about targetable

NOTE Confidence: 0.9486258

00:24:12.859 --> 00:24:14.060
mutations and how those play

NOTE Confidence: 0.9486258

00:24:14.060 --> 00:24:15.600
into, treatment selection.

NOTE Confidence: 0.9464896

00:24:16.540 --> 00:24:18.060
So, to sort of explain

NOTE Confidence: 0.9464896

00:24:18.060 --> 00:24:18.560
that,

NOTE Confidence: 0.975

00:24:20.300 --> 00:24:20.780
when,

NOTE Confidence: 0.97162217

00:24:21.340 --> 00:24:22.780
as the cancer is growing

NOTE Confidence: 0.97162217

00:24:22.780 --> 00:24:25.260
and becomes metastatic or, or

NOTE Confidence: 0.97162217

00:24:25.260 --> 00:24:26.780
continues to grow despite,

NOTE Confidence: 0.9940411

00:24:27.180 --> 00:24:28.160
despite medications,

NOTE Confidence: 0.89453006

00:24:29.045 --> 00:24:29.945
it's undergoing,

NOTE Confidence: 0.914296

00:24:30.325 --> 00:24:32.244
sometimes undergoing genetic changes and

NOTE Confidence: 0.914296

00:24:32.244 --> 00:24:32.744
developing,

NOTE Confidence: 0.9959024

00:24:33.205 --> 00:24:34.184
specific mutations.

NOTE Confidence: 0.9518162

00:24:34.965 --> 00:24:36.085
And in some cases, these

NOTE Confidence: 0.9518162

00:24:36.085 --> 00:24:37.924
mutations have drugs that, that

NOTE Confidence: 0.9518162

00:24:37.924 --> 00:24:39.765
are linked, drugs that, target

NOTE Confidence: 0.9518162

00:24:39.765 --> 00:24:41.365
those mutations effectively and can

NOTE Confidence: 0.9518162

00:24:41.365 --> 00:24:42.885
be particularly effective in those

NOTE Confidence: 0.9518162

00:24:42.885 --> 00:24:43.380
cancer

NOTE Confidence: 0.9749473

00:24:43.780 --> 00:24:44.740
types. But you need to

NOTE Confidence: 0.9749473

00:24:44.740 --> 00:24:46.260
have genetic testing to identify

NOTE Confidence: 0.9749473

00:24:46.260 --> 00:24:47.000
those mutations.

NOTE Confidence: 0.7253074

00:24:48.820 --> 00:24:49.320
Importantly,

NOTE Confidence: 0.9650237

00:24:49.780 --> 00:24:51.540
this sort of, the mutations

NOTE Confidence: 0.9650237

00:24:51.540 --> 00:24:52.820
I'm referring to refer to

NOTE Confidence: 0.9650237

00:24:52.820 --> 00:24:54.100
the mutations in the cancer

NOTE Confidence: 0.9650237

00:24:54.100 --> 00:24:56.020
cells. They're different from the

NOTE Confidence: 0.9650237

00:24:56.020 --> 00:24:56.520
mutations,

NOTE Confidence: 0.9818696

00:24:57.255 --> 00:24:58.135
that are in the healthy

NOTE Confidence: 0.9818696

00:24:58.135 --> 00:24:59.175
cells of, you know, a

NOTE Confidence: 0.9818696

00:24:59.175 --> 00:25:00.135
woman's body that might have

NOTE Confidence: 0.9818696

00:25:00.135 --> 00:25:01.335
been inherited by a family

NOTE Confidence: 0.9818696

00:25:01.335 --> 00:25:01.835
member.

NOTE Confidence: 0.9853614

00:25:02.375 --> 00:25:03.575
So this sort of genetic

NOTE Confidence: 0.9853614

00:25:03.575 --> 00:25:04.775
testing is different from the

NOTE Confidence: 0.9853614

00:25:04.775 --> 00:25:06.135
genetic testing that that many

NOTE Confidence: 0.9853614

00:25:06.135 --> 00:25:07.415
women undergo when they're first

NOTE Confidence: 0.9853614

00:25:07.415 --> 00:25:09.175
diagnosed, with with a breast

NOTE Confidence: 0.9853614

00:25:09.175 --> 00:25:09.675
cancer,

NOTE Confidence: 0.98786783

00:25:10.020 --> 00:25:10.760
be it metastatic

NOTE Confidence: 0.9221999

00:25:11.540 --> 00:25:12.440
or not metastatic.

NOTE Confidence: 0.98042923

00:25:13.780 --> 00:25:15.380
And it really includes testing

NOTE Confidence: 0.98042923

00:25:15.380 --> 00:25:16.760
the tumor tissue itself.

NOTE Confidence: 0.97120833

00:25:17.300 --> 00:25:18.420
As I mentioned, the mutations

NOTE Confidence: 0.97120833

00:25:18.420 --> 00:25:19.800
can guide treatment selection.

NOTE Confidence: 0.95675117

00:25:20.420 --> 00:25:21.859
And this testing can be

NOTE Confidence: 0.95675117

00:25:21.859 --> 00:25:23.140
performed in a few different

NOTE Confidence: 0.95675117

00:25:23.140 --> 00:25:25.165
ways. The most straightforward way

NOTE Confidence: 0.95675117

00:25:25.165 --> 00:25:27.325
probably is directly testing the

NOTE Confidence: 0.95675117

00:25:27.325 --> 00:25:29.085
tumor tissue itself. And that

NOTE Confidence: 0.95675117

00:25:29.085 --> 00:25:30.365
would require a biopsy of

NOTE Confidence: 0.95675117

00:25:30.365 --> 00:25:31.565
the tissue so that there

NOTE Confidence: 0.95675117

00:25:31.565 --> 00:25:32.925
was, you know, some tissue

NOTE Confidence: 0.95675117

00:25:32.925 --> 00:25:33.984
available for testing.

NOTE Confidence: 0.98037046

00:25:34.685 --> 00:25:36.685
Alternatively, sometimes you can do

NOTE Confidence: 0.98037046

00:25:36.685 --> 00:25:38.525
testing just on, using a

NOTE Confidence: 0.98037046

00:25:38.525 --> 00:25:39.570
simple blood draw.

NOTE Confidence: 0.9960534

00:25:39.970 --> 00:25:40.769
In that case,

NOTE Confidence: 0.9713117

00:25:41.730 --> 00:25:43.409
what's called circulating tumor DNA

NOTE Confidence: 0.9713117

00:25:43.409 --> 00:25:44.690
or DNA that's in the

NOTE Confidence: 0.9713117

00:25:44.690 --> 00:25:45.889
blood that's been shed by

NOTE Confidence: 0.9713117

00:25:45.889 --> 00:25:46.549
the cancer,

NOTE Confidence: 0.9983219

00:25:47.090 --> 00:25:49.090
can be isolated and tested

NOTE Confidence: 0.9983219

00:25:49.090 --> 00:25:49.830
for mutations.

NOTE Confidence: 0.9659195

00:25:51.330 --> 00:25:51.830
And

NOTE Confidence: 0.973952

00:25:52.289 --> 00:25:53.649
an important thing to also

NOTE Confidence: 0.973952

00:25:53.649 --> 00:25:54.915
keep in mind is that,

NOTE Confidence: 0.973952

00:25:55.075 --> 00:25:56.515
as I sort of described

NOTE Confidence: 0.973952

00:25:56.515 --> 00:25:57.635
a little bit already, these

NOTE Confidence: 0.973952

00:25:57.635 --> 00:25:59.655
mutations do have, a tendency

NOTE Confidence: 0.973952

00:25:59.715 --> 00:26:00.915
to develop and to change

NOTE Confidence: 0.973952

00:26:00.915 --> 00:26:01.575
over time.

NOTE Confidence: 0.9602912

00:26:02.115 --> 00:26:03.494
So, each time,

NOTE Confidence: 0.95235187

00:26:03.875 --> 00:26:05.234
a new treatment is being

NOTE Confidence: 0.95235187

00:26:05.234 --> 00:26:05.734
considered,

NOTE Confidence: 0.9832751

00:26:06.115 --> 00:26:07.555
it can sometimes be helpful

NOTE Confidence: 0.9832751

00:26:07.555 --> 00:26:09.255
to, to repeat testing.

NOTE Confidence: 0.8946417

00:26:11.190 --> 00:26:12.490
So, I said there was

NOTE Confidence: 0.8946417

00:26:12.630 --> 00:26:13.289
a circumstance

NOTE Confidence: 0.9955486

00:26:13.750 --> 00:26:15.669
for initial therapy where,

NOTE Confidence: 0.9462068

00:26:16.390 --> 00:26:18.330
where identifying a targetable mutation

NOTE Confidence: 0.9462068

00:26:18.390 --> 00:26:19.190
can be helpful.

NOTE Confidence: 0.93467945

00:26:19.909 --> 00:26:21.429
And, I'm going to describe

NOTE Confidence: 0.93467945

00:26:21.429 --> 00:26:22.250
that. So,

NOTE Confidence: 0.988568

00:26:22.710 --> 00:26:24.470
this is a relatively new

NOTE Confidence: 0.988568

00:26:24.470 --> 00:26:24.970
approach.

NOTE Confidence: 0.94093955

00:26:25.975 --> 00:26:27.815
The specific circumstance I'm referring

NOTE Confidence: 0.94093955

00:26:27.815 --> 00:26:29.095
to are for breast cancers

NOTE Confidence: 0.94093955

00:26:29.095 --> 00:26:30.715
that meet two criteria.

NOTE Confidence: 0.9991309

00:26:31.575 --> 00:26:32.315
The first

NOTE Confidence: 0.673509

00:26:33.014 --> 00:26:33.514
criteria

NOTE Confidence: 0.99287415

00:26:33.815 --> 00:26:35.034
is that the breast cancer

NOTE Confidence: 0.99287415

00:26:35.174 --> 00:26:35.674
recurred

NOTE Confidence: 0.9236212

00:26:36.695 --> 00:26:38.230
while a woman was taking

NOTE Confidence: 0.9236212

00:26:38.230 --> 00:26:39.990
what's called adjuvant endocrine therapy

NOTE Confidence: 0.9236212

00:26:39.990 --> 00:26:41.049
or kind of preventative,

NOTE Confidence: 0.93059665

00:26:41.669 --> 00:26:42.970
anti estrogen therapy,

NOTE Confidence: 0.99858683

00:26:43.590 --> 00:26:44.730
while she was in remission

NOTE Confidence: 0.99858683

00:26:44.789 --> 00:26:45.289
from

NOTE Confidence: 0.894333

00:26:45.590 --> 00:26:47.289
her early stage breast cancer,

NOTE Confidence: 0.98480594

00:26:47.669 --> 00:26:49.210
or the breast cancer recurred,

NOTE Confidence: 0.97012556

00:26:49.590 --> 00:26:50.789
within a year of finishing

NOTE Confidence: 0.97012556

00:26:50.789 --> 00:26:52.825
adjuvant endocrine therapy. And then

NOTE Confidence: 0.97012556

00:26:52.825 --> 00:26:54.345
in addition to that, the,

NOTE Confidence: 0.97012556

00:26:54.665 --> 00:26:56.025
breast cancer needs to have

NOTE Confidence: 0.97012556

00:26:56.025 --> 00:26:57.165
a, a PIK3CA

NOTE Confidence: 0.9967581

00:26:57.465 --> 00:26:57.965
mutation.

NOTE Confidence: 0.993196

00:27:00.185 --> 00:27:01.545
When those two criteria are

NOTE Confidence: 0.993196

00:27:01.545 --> 00:27:02.045
met,

NOTE Confidence: 0.9143152

00:27:02.425 --> 00:27:03.485
there is a new,

NOTE Confidence: 0.83041996

00:27:03.945 --> 00:27:05.625
combination of three drugs that

NOTE Confidence: 0.83041996

00:27:05.625 --> 00:27:06.355
can sometimes be helpful for,

NOTE Confidence: 0.83041996

00:27:06.360 --> 00:27:06.385
first line treatment for that

NOTE Confidence: 0.83041996

00:27:06.385 --> 00:27:06.415
initial treatment. And those three

NOTE Confidence: 0.83041996

00:27:06.415 --> 00:27:06.925
drugs are fulvestrant,

NOTE Confidence: 0.84283507

00:27:08.480 --> 00:27:09.300
treatment for that initial treatment.

NOTE Confidence: 0.97630554

00:27:10.240 --> 00:27:11.200
And those three drugs are

NOTE Confidence: 0.97630554

00:27:11.200 --> 00:27:11.700
fulvestrant,

NOTE Confidence: 0.80963814

00:27:12.400 --> 00:27:13.300
the older,

NOTE Confidence: 0.85768545

00:27:14.000 --> 00:27:16.660
endocrine therapy, I described earlier.

NOTE Confidence: 0.8971505

00:27:17.200 --> 00:27:17.700
Palbociclib,

NOTE Confidence: 0.91667646

00:27:18.080 --> 00:27:19.380
one of the CDK4six

NOTE Confidence: 0.96228176

00:27:19.760 --> 00:27:21.984
inhibitors from that first slide.

NOTE Confidence: 0.96228176

00:27:22.125 --> 00:27:23.345
And then a new medication

NOTE Confidence: 0.96228176

00:27:23.484 --> 00:27:23.984
called

NOTE Confidence: 0.6854807

00:27:24.285 --> 00:27:24.785
Involisib,

NOTE Confidence: 0.9644362

00:27:25.484 --> 00:27:27.505
which is a PI3 kinase

NOTE Confidence: 0.92822367

00:27:27.965 --> 00:27:29.405
inhibitor pill. It's an oral

NOTE Confidence: 0.92822367

00:27:29.405 --> 00:27:31.345
drug that targets this PIK3CA

NOTE Confidence: 0.92822367

00:27:31.484 --> 00:27:31.984
mutation.

NOTE Confidence: 0.90278006

00:27:34.380 --> 00:27:35.740
The advantage of this triple

NOTE Confidence: 0.90278006

00:27:35.740 --> 00:27:36.240
combination,

NOTE Confidence: 0.9757368

00:27:36.780 --> 00:27:38.300
therapy is that it works

NOTE Confidence: 0.9757368

00:27:38.300 --> 00:27:40.380
to control cancer for longer

NOTE Confidence: 0.9757368

00:27:40.380 --> 00:27:42.160
than just fulvestrant and poblociclib

NOTE Confidence: 0.95713603

00:27:42.540 --> 00:27:43.200
by themselves.

NOTE Confidence: 0.9724906

00:27:43.980 --> 00:27:45.500
So, it can control cancer

NOTE Confidence: 0.9724906

00:27:45.500 --> 00:27:46.700
in about sixty percent of

NOTE Confidence: 0.9724906

00:27:46.700 --> 00:27:49.065
women as compared to, just

NOTE Confidence: 0.9724906

00:27:49.065 --> 00:27:50.105
about a quarter of women,

NOTE Confidence: 0.9724906

00:27:50.265 --> 00:27:52.044
with that set of circumstances

NOTE Confidence: 0.9724906

00:27:52.105 --> 00:27:52.845
I described,

NOTE Confidence: 0.9603384

00:27:53.785 --> 00:27:55.225
when you're using just those

NOTE Confidence: 0.9603384

00:27:55.225 --> 00:27:55.965
two drugs.

NOTE Confidence: 0.93001705

00:27:56.665 --> 00:27:57.965
In addition to,

NOTE Confidence: 0.9552279

00:27:58.505 --> 00:28:00.424
controlling cancer in more women,

NOTE Confidence: 0.9552279

00:28:00.424 --> 00:28:01.865
it also controls cancer for

NOTE Confidence: 0.9552279

00:28:01.865 --> 00:28:02.880
longer, typically

NOTE Confidence: 0.87282336

00:28:06.640 --> 00:28:07.859
it seems to work considerably

NOTE Confidence: 0.9359503

00:28:08.560 --> 00:28:09.680
better than the old,

NOTE Confidence: 0.9933051

00:28:10.560 --> 00:28:11.940
two pair of medications.

NOTE Confidence: 0.9734066

00:28:13.280 --> 00:28:15.440
A tricky thing about these

NOTE Confidence: 0.9734066

00:28:15.440 --> 00:28:17.200
combinations of multiple drugs is

NOTE Confidence: 0.9734066

00:28:17.200 --> 00:28:18.805
that as you add more

NOTE Confidence: 0.9734066

00:28:18.805 --> 00:28:20.485
drugs, you do often see

NOTE Confidence: 0.9734066

00:28:20.485 --> 00:28:21.845
more side effects and that

NOTE Confidence: 0.9734066

00:28:21.845 --> 00:28:23.225
can be a challenge.

NOTE Confidence: 0.98063874

00:28:24.085 --> 00:28:25.205
And that was indeed the

NOTE Confidence: 0.98063874

00:28:25.205 --> 00:28:26.665
case with these medications.

NOTE Confidence: 0.8406186

00:28:27.045 --> 00:28:28.105
So side effects

NOTE Confidence: 0.94292283

00:28:28.485 --> 00:28:29.880
that are common with these

NOTE Confidence: 0.94292283

00:28:29.880 --> 00:28:31.020
three drugs together

NOTE Confidence: 0.951663

00:28:31.400 --> 00:28:33.080
include diarrhea, mouth sores, and

NOTE Confidence: 0.951663

00:28:33.080 --> 00:28:34.619
sometimes high blood sugar levels.

NOTE Confidence: 0.9330601

00:28:35.080 --> 00:28:36.840
So, just as important as

NOTE Confidence: 0.9330601

00:28:36.840 --> 00:28:37.880
finding the right,

NOTE Confidence: 0.9017013

00:28:38.360 --> 00:28:39.260
cancer treatment,

NOTE Confidence: 0.96627426

00:28:40.040 --> 00:28:40.920
the other thing you have

NOTE Confidence: 0.96627426

00:28:40.920 --> 00:28:42.060
to do with your oncologist

NOTE Confidence: 0.96627426

00:28:42.200 --> 00:28:43.915
and that we spend a

NOTE Confidence: 0.96627426

00:28:43.915 --> 00:28:45.035
lot of time doing is

NOTE Confidence: 0.96627426

00:28:45.035 --> 00:28:46.235
working together on trying to

NOTE Confidence: 0.96627426

00:28:46.235 --> 00:28:47.295
control side effects.

NOTE Confidence: 0.9548174

00:28:48.875 --> 00:28:50.075
Okay. So, moving on to

NOTE Confidence: 0.9548174

00:28:50.075 --> 00:28:50.955
the to the,

NOTE Confidence: 0.9458916

00:28:51.435 --> 00:28:52.255
second treatment.

NOTE Confidence: 0.7689415

00:28:54.875 --> 00:28:55.375
The,

NOTE Confidence: 0.88947266

00:28:57.460 --> 00:28:58.340
or moving on to the

NOTE Confidence: 0.88947266

00:28:58.340 --> 00:29:00.039
second line therapy, excuse me.

NOTE Confidence: 0.97839737

00:29:00.740 --> 00:29:02.360
For a long time after,

NOTE Confidence: 0.92123604

00:29:02.820 --> 00:29:03.220
that,

NOTE Confidence: 0.93865246

00:29:03.700 --> 00:29:04.840
aromatase inhibitor,

NOTE Confidence: 0.9796914

00:29:05.620 --> 00:29:07.299
treatment stops working in the

NOTE Confidence: 0.9796914

00:29:07.299 --> 00:29:08.679
in the first line setting,

NOTE Confidence: 0.9796914

00:29:08.740 --> 00:29:09.940
the standard approach was to

NOTE Confidence: 0.9796914

00:29:09.940 --> 00:29:11.415
move on to this, fulvestrant

NOTE Confidence: 0.9796914

00:29:11.415 --> 00:29:11.915
medication.

NOTE Confidence: 0.98153704

00:29:12.455 --> 00:29:14.775
Fulvestrant is an intramuscular injection

NOTE Confidence: 0.98153704

00:29:14.775 --> 00:29:15.655
that you have to receive

NOTE Confidence: 0.98153704

00:29:15.655 --> 00:29:17.755
every four weeks, which is,

NOTE Confidence: 0.92220515

00:29:18.775 --> 00:29:19.515
is not necessarily

NOTE Confidence: 0.98597926

00:29:20.375 --> 00:29:21.335
a pleasant treatment to be

NOTE Confidence: 0.98597926

00:29:21.335 --> 00:29:21.835
receiving.

NOTE Confidence: 0.77374804

00:29:22.855 --> 00:29:23.355
And,

NOTE Confidence: 0.83778095

00:29:24.410 --> 00:29:26.010
on its own, its response

NOTE Confidence: 0.83778095

00:29:26.010 --> 00:29:27.390
time or the response,

NOTE Confidence: 0.9817956

00:29:27.770 --> 00:29:29.450
time of the cancer is

NOTE Confidence: 0.9817956

00:29:29.450 --> 00:29:31.049
not always as long as

NOTE Confidence: 0.9817956

00:29:31.049 --> 00:29:31.870
we would hope.

NOTE Confidence: 0.93711555

00:29:32.410 --> 00:29:33.450
And so, there have been

NOTE Confidence: 0.93711555

00:29:33.450 --> 00:29:34.090
a number of,

NOTE Confidence: 0.9717689

00:29:34.809 --> 00:29:35.630
different options,

NOTE Confidence: 0.9354659

00:29:36.090 --> 00:29:37.289
that have been developed recently

NOTE Confidence: 0.9354659

00:29:37.289 --> 00:29:38.730
to try and improve on

NOTE Confidence: 0.9354659

00:29:38.730 --> 00:29:39.470
those outcomes,

NOTE Confidence: 0.91887265

00:29:40.065 --> 00:29:41.264
and to improve on the

NOTE Confidence: 0.91887265

00:29:41.264 --> 00:29:42.784
just the experience of receiving

NOTE Confidence: 0.91887265

00:29:42.784 --> 00:29:43.445
the drug.

NOTE Confidence: 0.9375552

00:29:44.705 --> 00:29:46.465
So, the first options I'll

NOTE Confidence: 0.9375552

00:29:46.465 --> 00:29:47.745
go through are drugs that

NOTE Confidence: 0.9375552

00:29:47.745 --> 00:29:49.445
target the ESR1 mutation.

NOTE Confidence: 0.991859

00:29:51.345 --> 00:29:52.465
The first of those is

NOTE Confidence: 0.991859

00:29:52.465 --> 00:29:53.524
a medication called

NOTE Confidence: 0.94489974

00:29:54.090 --> 00:29:55.289
Elisestrin. Elisestrin has been on

NOTE Confidence: 0.94489974

00:29:55.289 --> 00:29:56.410
the market for about two

NOTE Confidence: 0.94489974

00:29:56.410 --> 00:29:57.150
years now.

NOTE Confidence: 0.9554104

00:29:57.690 --> 00:29:59.130
It's a pill. It's not

NOTE Confidence: 0.9554104

00:29:59.130 --> 00:30:00.169
an injection. It's a pill

NOTE Confidence: 0.9554104

00:30:00.169 --> 00:30:01.710
that has the same mechanism

NOTE Confidence: 0.8916269

00:30:02.010 --> 00:30:03.370
as fulvestrin. It's what was

NOTE Confidence: 0.8916269

00:30:03.370 --> 00:30:05.370
called a selective estrogen receptor

NOTE Confidence: 0.8916269

00:30:05.370 --> 00:30:05.870
degrader.

NOTE Confidence: 0.9451719

00:30:07.525 --> 00:30:09.925
And, compared to fulvestrant in

NOTE Confidence: 0.9451719

00:30:09.925 --> 00:30:11.304
women who have an ESR1

NOTE Confidence: 0.9451719

00:30:11.445 --> 00:30:11.945
mutation,

NOTE Confidence: 0.9839153

00:30:12.725 --> 00:30:14.725
it controls cancer longer. So,

NOTE Confidence: 0.9839153

00:30:14.725 --> 00:30:16.105
it works better than fulvestrant

NOTE Confidence: 0.9839153

00:30:16.245 --> 00:30:17.205
in addition to being an

NOTE Confidence: 0.9839153

00:30:17.205 --> 00:30:18.804
oral medication for women with

NOTE Confidence: 0.9839153

00:30:18.804 --> 00:30:20.025
an ESR1 mutation.

NOTE Confidence: 0.9451022

00:30:21.020 --> 00:30:22.299
It seems to work best

NOTE Confidence: 0.9451022

00:30:22.299 --> 00:30:23.820
and really that extra benefit

NOTE Confidence: 0.9451022

00:30:23.820 --> 00:30:25.100
is mostly seen in women

NOTE Confidence: 0.9451022

00:30:25.100 --> 00:30:26.299
who have, were able,

NOTE Confidence: 0.9793501

00:30:27.100 --> 00:30:28.380
whose cancer was controlled for

NOTE Confidence: 0.9793501

00:30:28.380 --> 00:30:29.980
at least twelve months, on

NOTE Confidence: 0.9793501

00:30:29.980 --> 00:30:31.580
their first line anti estrogen

NOTE Confidence: 0.9793501

00:30:31.580 --> 00:30:32.080
therapy.

NOTE Confidence: 0.9461473

00:30:32.855 --> 00:30:34.215
So those are women who,

NOTE Confidence: 0.9461473

00:30:34.215 --> 00:30:35.095
you know, it seems like

NOTE Confidence: 0.9461473

00:30:35.095 --> 00:30:37.095
their cancer is still sensitive

NOTE Confidence: 0.9461473

00:30:37.095 --> 00:30:38.555
to anti estrogen therapies.

NOTE Confidence: 0.9461854

00:30:39.495 --> 00:30:40.615
And it can have some

NOTE Confidence: 0.9461854

00:30:40.615 --> 00:30:41.975
side effects, but usually they're

NOTE Confidence: 0.9461854

00:30:41.975 --> 00:30:42.715
not particularly,

NOTE Confidence: 0.96630067

00:30:43.175 --> 00:30:44.535
difficult. It can have a

NOTE Confidence: 0.96630067

00:30:44.535 --> 00:30:45.995
variety of GI side effects.

NOTE Confidence: 0.9696819

00:30:46.360 --> 00:30:47.040
And can have some of

NOTE Confidence: 0.9696819

00:30:47.040 --> 00:30:48.360
the same sort of anti

NOTE Confidence: 0.9696819

00:30:48.360 --> 00:30:50.120
estrogen menopause type side effects

NOTE Confidence: 0.9696819

00:30:50.120 --> 00:30:51.000
that you see with other

NOTE Confidence: 0.9696819

00:30:51.000 --> 00:30:52.220
anti estrogen medications.

NOTE Confidence: 0.94356424

00:30:54.440 --> 00:30:55.500
There is a,

NOTE Confidence: 0.90034246

00:30:56.360 --> 00:30:58.059
practically brand new option,

NOTE Confidence: 0.9416598

00:30:58.840 --> 00:31:00.655
for women with ESR one

NOTE Confidence: 0.9416598

00:31:00.655 --> 00:31:02.335
mutations, that is is similar

NOTE Confidence: 0.9416598

00:31:02.335 --> 00:31:03.715
in some ways to elocestrant.

NOTE Confidence: 0.9416598

00:31:03.855 --> 00:31:06.035
It's called, illumin illuminestrant.

NOTE Confidence: 0.94801027

00:31:07.055 --> 00:31:07.935
Also a lot of vowels

NOTE Confidence: 0.94801027

00:31:07.935 --> 00:31:08.755
in that one.

NOTE Confidence: 0.9592932

00:31:09.295 --> 00:31:10.815
It is also an oral

NOTE Confidence: 0.9592932

00:31:10.815 --> 00:31:12.515
SIRD, just like the elocestrant.

NOTE Confidence: 0.9167147

00:31:14.470 --> 00:31:16.010
And, just like elacestrant,

NOTE Confidence: 0.9314298

00:31:16.950 --> 00:31:18.710
it controls cancer for longer

NOTE Confidence: 0.9314298

00:31:18.710 --> 00:31:20.309
than fulvestrant amongst women with

NOTE Confidence: 0.9314298

00:31:20.309 --> 00:31:21.370
ESRO mutations.

NOTE Confidence: 0.99503094

00:31:22.309 --> 00:31:23.429
What makes it a little

NOTE Confidence: 0.99503094

00:31:23.429 --> 00:31:24.549
bit different is that in

NOTE Confidence: 0.99503094

00:31:24.549 --> 00:31:25.049
the

NOTE Confidence: 0.9855346

00:31:25.525 --> 00:31:26.645
trial that led to its

NOTE Confidence: 0.9855346

00:31:26.645 --> 00:31:27.145
approval,

NOTE Confidence: 0.97527266

00:31:27.605 --> 00:31:29.365
there was a a third

NOTE Confidence: 0.97527266

00:31:29.365 --> 00:31:30.745
group of women who received,

NOTE Confidence: 0.7895758

00:31:31.525 --> 00:31:33.765
the, in luminescent in combination

NOTE Confidence: 0.7895758

00:31:33.765 --> 00:31:34.425
with the bemiciclib.

NOTE Confidence: 0.99189514

00:31:35.445 --> 00:31:36.485
And in that group of

NOTE Confidence: 0.99189514

00:31:36.485 --> 00:31:36.985
women,

NOTE Confidence: 0.96671844

00:31:37.285 --> 00:31:38.575
the amount of time the

NOTE Confidence: 0.96671844

00:31:38.575 --> 00:31:39.060
cancer

NOTE Confidence: 0.98724765

00:31:39.460 --> 00:31:41.220
even longer than with either

NOTE Confidence: 0.98724765

00:31:41.220 --> 00:31:42.980
of the the single agent

NOTE Confidence: 0.98724765

00:31:42.980 --> 00:31:43.480
drugs.

NOTE Confidence: 0.9879855

00:31:44.260 --> 00:31:45.460
That use has not been

NOTE Confidence: 0.9879855

00:31:45.460 --> 00:31:47.060
fully reviewed and approved by

NOTE Confidence: 0.9879855

00:31:47.060 --> 00:31:48.260
the FDA yet, but it's

NOTE Confidence: 0.9879855

00:31:48.260 --> 00:31:49.860
something that that might be,

NOTE Confidence: 0.9987264

00:31:50.580 --> 00:31:51.620
might have potential in the

NOTE Confidence: 0.9987264

00:31:51.620 --> 00:31:52.120
future.

NOTE Confidence: 0.9636986

00:31:52.605 --> 00:31:53.565
And as I mentioned, this

NOTE Confidence: 0.9636986

00:31:53.565 --> 00:31:54.525
drug was just approved by

NOTE Confidence: 0.9636986

00:31:54.525 --> 00:31:55.565
the FDA towards the end

NOTE Confidence: 0.9636986

00:31:55.565 --> 00:31:56.925
of September. So it's it's,

NOTE Confidence: 0.9636986

00:31:57.245 --> 00:31:58.205
just kind of coming,

NOTE Confidence: 0.99913853

00:31:59.485 --> 00:32:01.505
it's just becoming widely available.

NOTE Confidence: 0.91969

00:32:05.325 --> 00:32:05.825
The,

NOTE Confidence: 0.81450135

00:32:08.510 --> 00:32:09.789
in addition to those oral

NOTE Confidence: 0.81450135

00:32:09.789 --> 00:32:10.289
sird,

NOTE Confidence: 0.97332805

00:32:10.669 --> 00:32:12.289
there's a there are some

NOTE Confidence: 0.97332805

00:32:12.429 --> 00:32:13.950
other types of medications, some

NOTE Confidence: 0.97332805

00:32:13.950 --> 00:32:15.730
other some medications with alternative

NOTE Confidence: 0.97332805

00:32:15.789 --> 00:32:17.010
mechanisms of action,

NOTE Confidence: 0.8297876

00:32:17.630 --> 00:32:18.669
for women with the ESR

NOTE Confidence: 0.8297876

00:32:18.669 --> 00:32:19.330
one mutation.

NOTE Confidence: 0.9720749

00:32:20.030 --> 00:32:21.390
One example of that is

NOTE Confidence: 0.9720749

00:32:21.390 --> 00:32:23.010
a medication called veptigestrin.

NOTE Confidence: 0.9543788

00:32:24.164 --> 00:32:25.445
It is a pill with

NOTE Confidence: 0.9543788

00:32:25.445 --> 00:32:26.904
a, with a slightly different,

NOTE Confidence: 0.90963805

00:32:27.445 --> 00:32:28.085
sort of,

NOTE Confidence: 0.9986271

00:32:28.485 --> 00:32:29.625
mechanism for

NOTE Confidence: 0.9064227

00:32:30.164 --> 00:32:31.845
destroying or degrading the estrogen

NOTE Confidence: 0.9064227

00:32:31.845 --> 00:32:32.345
receptor.

NOTE Confidence: 0.9785153

00:32:33.284 --> 00:32:35.384
It also increases time on,

NOTE Confidence: 0.9958005

00:32:35.764 --> 00:32:36.424
of control

NOTE Confidence: 0.78353035

00:32:36.804 --> 00:32:38.030
of the cancer and when

NOTE Confidence: 0.78353035

00:32:38.030 --> 00:32:39.289
with ESR1 mutations.

NOTE Confidence: 0.95359963

00:32:39.909 --> 00:32:41.429
This has been studied and,

NOTE Confidence: 0.95359963

00:32:41.669 --> 00:32:43.830
these results have been, shared

NOTE Confidence: 0.95359963

00:32:43.830 --> 00:32:45.750
with, the scientific community, but

NOTE Confidence: 0.95359963

00:32:45.750 --> 00:32:46.870
it hasn't been approved by

NOTE Confidence: 0.95359963

00:32:46.870 --> 00:32:48.070
the FDA yet. It's under

NOTE Confidence: 0.95359963

00:32:48.070 --> 00:32:50.070
review. So, potentially sometime in

NOTE Confidence: 0.95359963

00:32:50.070 --> 00:32:51.270
the next year, it'll become

NOTE Confidence: 0.95359963

00:32:51.270 --> 00:32:52.409
available as well.

NOTE Confidence: 0.98425055

00:32:54.125 --> 00:32:55.664
So, moving on from ESR1,

NOTE Confidence: 0.98425055

00:32:55.804 --> 00:32:56.605
what about some of the

NOTE Confidence: 0.98425055

00:32:56.605 --> 00:32:58.044
other, mutations that we look

NOTE Confidence: 0.98425055

00:32:58.044 --> 00:32:58.544
for?

NOTE Confidence: 0.99672854

00:32:59.485 --> 00:33:00.684
There are a group of

NOTE Confidence: 0.99672854

00:33:00.684 --> 00:33:01.644
mutations that are part of

NOTE Confidence: 0.99672854

00:33:01.644 --> 00:33:02.845
what we call the AKT

NOTE Confidence: 0.99672854

00:33:02.845 --> 00:33:03.345
pathway.

NOTE Confidence: 0.971194

00:33:03.725 --> 00:33:05.245
The AKT pathway is an

NOTE Confidence: 0.971194

00:33:05.245 --> 00:33:05.745
alternative,

NOTE Confidence: 0.9804927

00:33:06.205 --> 00:33:08.384
pathway that, leads to resistance,

NOTE Confidence: 0.9131305

00:33:08.940 --> 00:33:10.159
sometimes to,

NOTE Confidence: 0.9761971

00:33:10.539 --> 00:33:12.399
standard anti estrogen therapies.

NOTE Confidence: 0.96159124

00:33:12.779 --> 00:33:13.659
And there are a number

NOTE Confidence: 0.96159124

00:33:13.659 --> 00:33:14.700
of genes that are involved

NOTE Confidence: 0.96159124

00:33:14.700 --> 00:33:15.820
in the pathway, but three

NOTE Confidence: 0.96159124

00:33:15.820 --> 00:33:17.019
in particular that can be

NOTE Confidence: 0.96159124

00:33:17.019 --> 00:33:19.519
targeted are the, PIK3CA mutation

NOTE Confidence: 0.86467373

00:33:19.980 --> 00:33:21.740
or gene, the AKT1 gene

NOTE Confidence: 0.86467373

00:33:21.740 --> 00:33:22.635
and the P10 gene.

NOTE Confidence: 0.9843324

00:33:23.515 --> 00:33:24.955
So, when mutations in those

NOTE Confidence: 0.9843324

00:33:24.955 --> 00:33:25.935
genes are seen,

NOTE Confidence: 0.9749616

00:33:26.315 --> 00:33:27.355
a medication that can be

NOTE Confidence: 0.9749616

00:33:27.355 --> 00:33:29.935
useful in combination with, fulvestrant

NOTE Confidence: 0.9749616

00:33:30.155 --> 00:33:31.055
is called capivacertib

NOTE Confidence: 0.841188

00:33:31.595 --> 00:33:33.435
or, TrueCap is the, the

NOTE Confidence: 0.841188

00:33:33.435 --> 00:33:34.415
brand name there.

NOTE Confidence: 0.8881636

00:33:35.640 --> 00:33:36.380
It is,

NOTE Confidence: 0.9294471

00:33:36.920 --> 00:33:38.760
targeting the similar part of

NOTE Confidence: 0.9294471

00:33:38.760 --> 00:33:41.080
the, of cell communication as

NOTE Confidence: 0.9294471

00:33:41.080 --> 00:33:42.300
this older medication,

NOTE Confidence: 0.8470059

00:33:42.680 --> 00:33:43.800
called pick Ray that many

NOTE Confidence: 0.8470059

00:33:43.800 --> 00:33:44.520
of you may have heard

NOTE Confidence: 0.8470059

00:33:44.520 --> 00:33:45.020
of.

NOTE Confidence: 0.8366912

00:33:45.320 --> 00:33:46.300
Pick Ray is,

NOTE Confidence: 0.9581654

00:33:46.680 --> 00:33:48.200
is an older oral drug,

NOTE Confidence: 0.9581654

00:33:48.520 --> 00:33:49.815
that has a lot of

NOTE Confidence: 0.9581654

00:33:49.815 --> 00:33:50.375
side effects,

NOTE Confidence: 0.95412433

00:33:50.775 --> 00:33:52.934
and was difficult to use,

NOTE Confidence: 0.95412433

00:33:53.095 --> 00:33:54.215
I think, for many women

NOTE Confidence: 0.95412433

00:33:54.215 --> 00:33:55.895
because of the degree of

NOTE Confidence: 0.95412433

00:33:55.895 --> 00:33:56.554
side effects,

NOTE Confidence: 0.997204

00:33:57.015 --> 00:33:58.315
that came along with it.

NOTE Confidence: 0.9052887

00:33:59.015 --> 00:33:59.515
Cabivastatinib

NOTE Confidence: 0.9626931

00:34:00.054 --> 00:34:01.560
is approved for all three

NOTE Confidence: 0.9626931

00:34:01.800 --> 00:34:03.400
of these mutations or for

NOTE Confidence: 0.9626931

00:34:03.400 --> 00:34:04.520
use in women whose cancer

NOTE Confidence: 0.9626931

00:34:04.520 --> 00:34:05.320
has all three of these

NOTE Confidence: 0.9626931

00:34:05.320 --> 00:34:06.440
mutations or any of them.

NOTE Confidence: 0.9626931

00:34:06.440 --> 00:34:07.240
They don't have all three

NOTE Confidence: 0.9626931

00:34:07.240 --> 00:34:08.280
at once, just any one

NOTE Confidence: 0.9626931

00:34:08.280 --> 00:34:08.860
of them.

NOTE Confidence: 0.993023

00:34:10.040 --> 00:34:10.920
And it seems to be

NOTE Confidence: 0.993023

00:34:10.920 --> 00:34:12.280
useful in women who have

NOTE Confidence: 0.993023

00:34:12.280 --> 00:34:12.760
spent,

NOTE Confidence: 0.9890956

00:34:13.160 --> 00:34:14.680
even less than twelve months

NOTE Confidence: 0.9890956

00:34:14.680 --> 00:34:16.360
on, their first line endocrine

NOTE Confidence: 0.9890956

00:34:16.360 --> 00:34:16.860
therapy.

NOTE Confidence: 0.94476163

00:34:17.614 --> 00:34:18.494
It can cause some side

NOTE Confidence: 0.94476163

00:34:18.494 --> 00:34:20.094
effects, some GI side effects,

NOTE Confidence: 0.94476163

00:34:20.094 --> 00:34:21.375
and some rash. It doesn't

NOTE Confidence: 0.94476163

00:34:21.375 --> 00:34:22.815
cause as much, high blood

NOTE Confidence: 0.94476163

00:34:22.815 --> 00:34:24.414
sugar as the PICRae, but

NOTE Confidence: 0.94476163

00:34:24.414 --> 00:34:25.614
it does still require blood

NOTE Confidence: 0.94476163

00:34:25.614 --> 00:34:26.434
sugar monitoring.

NOTE Confidence: 0.9834849

00:34:28.575 --> 00:34:29.075
And

NOTE Confidence: 0.9736075

00:34:30.350 --> 00:34:31.790
sometimes, I mean, really not

NOTE Confidence: 0.9736075

00:34:31.950 --> 00:34:33.469
it's not rare that a

NOTE Confidence: 0.9736075

00:34:33.469 --> 00:34:33.950
woman,

NOTE Confidence: 0.94976306

00:34:34.350 --> 00:34:36.110
when she progresses on first

NOTE Confidence: 0.94976306

00:34:36.110 --> 00:34:37.469
line therapy might not have

NOTE Confidence: 0.94976306

00:34:37.469 --> 00:34:38.610
any target mutations.

NOTE Confidence: 0.9356574

00:34:39.310 --> 00:34:40.750
And so, in that case,

NOTE Confidence: 0.9356574

00:34:40.750 --> 00:34:42.444
we ask questions like, should

NOTE Confidence: 0.9356574

00:34:42.444 --> 00:34:43.325
we keep going with our

NOTE Confidence: 0.9356574

00:34:43.325 --> 00:34:43.825
CDK4six

NOTE Confidence: 0.96859264

00:34:44.204 --> 00:34:45.724
inhibitor when we change the

NOTE Confidence: 0.96859264

00:34:45.724 --> 00:34:47.585
underlying anti estrogen medication?

NOTE Confidence: 0.90228254

00:34:48.045 --> 00:34:49.005
There have been a couple

NOTE Confidence: 0.90228254

00:34:49.005 --> 00:34:50.765
of different trials, or more

NOTE Confidence: 0.90228254

00:34:50.765 --> 00:34:52.045
than two, but I'll talk

NOTE Confidence: 0.90228254

00:34:52.045 --> 00:34:52.785
about two,

NOTE Confidence: 0.91007227

00:34:53.805 --> 00:34:55.480
that look at this question.

NOTE Confidence: 0.91007227

00:34:55.719 --> 00:34:56.920
The first of those was

NOTE Confidence: 0.91007227

00:34:56.920 --> 00:34:58.140
called the PACE trial.

NOTE Confidence: 0.8267944

00:34:58.520 --> 00:34:59.820
And the PACE trial,

NOTE Confidence: 0.9046329

00:35:01.239 --> 00:35:02.920
looked at or had two

NOTE Confidence: 0.9046329

00:35:02.920 --> 00:35:03.880
groups of women in it.

NOTE Confidence: 0.9046329

00:35:03.880 --> 00:35:05.880
Women who progressed on, their

NOTE Confidence: 0.9046329

00:35:05.880 --> 00:35:07.160
first line treatment with their

NOTE Confidence: 0.9046329

00:35:07.160 --> 00:35:08.920
CDK foursix inhibitor. And they

NOTE Confidence: 0.9046329

00:35:08.920 --> 00:35:10.364
received either full vestrant, the

NOTE Confidence: 0.9046329

00:35:10.364 --> 00:35:10.864
standard,

NOTE Confidence: 0.9065598

00:35:11.325 --> 00:35:12.765
approach by itself or full

NOTE Confidence: 0.9065598

00:35:12.765 --> 00:35:13.905
vestrant with pelbociclib.

NOTE Confidence: 0.98812354

00:35:14.685 --> 00:35:15.725
Now, most of the women

NOTE Confidence: 0.98812354

00:35:15.725 --> 00:35:16.844
in that trial had gotten

NOTE Confidence: 0.98812354

00:35:16.844 --> 00:35:17.344
pelbociclib

NOTE Confidence: 0.9907749

00:35:17.645 --> 00:35:18.625
as their first CDK4six

NOTE Confidence: 0.9573889

00:35:19.085 --> 00:35:20.364
inhibitor also. So, this was

NOTE Confidence: 0.9573889

00:35:20.364 --> 00:35:21.565
really a continuation of the

NOTE Confidence: 0.9573889

00:35:21.565 --> 00:35:22.065
same,

NOTE Confidence: 0.9939747

00:35:23.120 --> 00:35:24.400
the same drug for these

NOTE Confidence: 0.9939747

00:35:24.400 --> 00:35:26.100
women, generally speaking.

NOTE Confidence: 0.99747676

00:35:26.960 --> 00:35:27.460
And

NOTE Confidence: 0.94837546

00:35:28.080 --> 00:35:30.100
when using this approach, unfortunately,

NOTE Confidence: 0.94837546

00:35:30.160 --> 00:35:31.520
there wasn't really any sort

NOTE Confidence: 0.94837546

00:35:31.520 --> 00:35:33.040
of improvement in how, how

NOTE Confidence: 0.94837546

00:35:33.040 --> 00:35:34.420
well fobesterone performed.

NOTE Confidence: 0.957304

00:35:34.880 --> 00:35:35.940
The cancer progressed,

NOTE Confidence: 0.97098243

00:35:36.320 --> 00:35:37.440
at the same kind of

NOTE Confidence: 0.97098243

00:35:37.440 --> 00:35:38.660
pace in both

NOTE Confidence: 0.99388504

00:35:39.015 --> 00:35:39.914
groups of women.

NOTE Confidence: 0.95648646

00:35:40.694 --> 00:35:41.815
But what if we switch?

NOTE Confidence: 0.95648646

00:35:41.974 --> 00:35:42.855
What if we change the

NOTE Confidence: 0.95648646

00:35:42.855 --> 00:35:44.375
CDK4six inhibitor to one of

NOTE Confidence: 0.95648646

00:35:44.375 --> 00:35:45.174
the other two?

NOTE Confidence: 0.9327145

00:35:45.974 --> 00:35:47.255
So the Maintain trial gave

NOTE Confidence: 0.9327145

00:35:47.255 --> 00:35:48.535
us some information about that

NOTE Confidence: 0.9327145

00:35:48.535 --> 00:35:49.015
approach.

NOTE Confidence: 0.9776795

00:35:49.335 --> 00:35:50.075
It compared,

NOTE Confidence: 0.8933046

00:35:51.255 --> 00:35:52.614
in second line therapy in

NOTE Confidence: 0.8933046

00:35:52.614 --> 00:35:53.494
women who had gotten the

NOTE Confidence: 0.8933046

00:35:53.494 --> 00:35:53.994
CDK4six

NOTE Confidence: 0.908614

00:35:54.570 --> 00:35:56.730
inhibitor. It compared new endocrine

NOTE Confidence: 0.908614

00:35:56.730 --> 00:35:58.570
therapy alone or new anti

NOTE Confidence: 0.908614

00:35:58.570 --> 00:36:00.590
estrogen therapy plus ribo cyclob.

NOTE Confidence: 0.97376114

00:36:00.890 --> 00:36:02.010
And for about eighty eight

NOTE Confidence: 0.97376114

00:36:02.010 --> 00:36:03.210
percent of patients in that,

NOTE Confidence: 0.97376114

00:36:03.530 --> 00:36:04.030
study,

NOTE Confidence: 0.9317087

00:36:04.570 --> 00:36:06.170
that ribo cyclob was a

NOTE Confidence: 0.9317087

00:36:06.170 --> 00:36:07.715
change. It was different CDK4six

NOTE Confidence: 0.9317087

00:36:07.935 --> 00:36:09.875
inhibitor than what they previously

NOTE Confidence: 0.9317087

00:36:09.935 --> 00:36:10.435
received.

NOTE Confidence: 0.7727095

00:36:10.975 --> 00:36:12.515
In that case, the fulvestrant,

NOTE Confidence: 0.9628113

00:36:12.895 --> 00:36:13.635
with ribociclib,

NOTE Confidence: 0.93634653

00:36:14.335 --> 00:36:15.135
did improve,

NOTE Confidence: 0.99940634

00:36:15.455 --> 00:36:16.435
time on therapy.

NOTE Confidence: 0.9722369

00:36:16.815 --> 00:36:18.175
So, this doesn't, you know,

NOTE Confidence: 0.9722369

00:36:18.175 --> 00:36:19.215
kind of tell us about

NOTE Confidence: 0.9722369

00:36:19.215 --> 00:36:21.475
every situation with, switching CDK4six

NOTE Confidence: 0.98260415

00:36:21.849 --> 00:36:22.890
inhibitors, but it does give

NOTE Confidence: 0.98260415

00:36:22.890 --> 00:36:23.770
us some reason to believe

NOTE Confidence: 0.98260415

00:36:23.770 --> 00:36:24.969
that, that they might be

NOTE Confidence: 0.98260415

00:36:24.969 --> 00:36:26.329
useful, if there are no

NOTE Confidence: 0.98260415

00:36:26.329 --> 00:36:27.950
targetable mutations present.

NOTE Confidence: 0.9468561

00:36:30.170 --> 00:36:31.050
For the for the sake

NOTE Confidence: 0.9468561

00:36:31.050 --> 00:36:31.849
of time and for the

NOTE Confidence: 0.9468561

00:36:31.849 --> 00:36:33.150
sake of allowing questions,

NOTE Confidence: 0.9478113

00:36:33.530 --> 00:36:35.625
I'm, I'm gonna, not really

NOTE Confidence: 0.9478113

00:36:35.625 --> 00:36:38.025
talk, specifically about medication, you

NOTE Confidence: 0.9478113

00:36:38.025 --> 00:36:39.725
know, non anti estrogen medications

NOTE Confidence: 0.9478113

00:36:39.945 --> 00:36:42.105
for, hormone receptor positive breast

NOTE Confidence: 0.9478113

00:36:42.105 --> 00:36:43.385
cancer. But, but I will

NOTE Confidence: 0.9478113

00:36:43.385 --> 00:36:44.985
say, also just a little

NOTE Confidence: 0.9478113

00:36:44.985 --> 00:36:46.425
bit about, trial options that

NOTE Confidence: 0.9478113

00:36:46.425 --> 00:36:47.305
are available at the, at

NOTE Confidence: 0.9478113

00:36:47.305 --> 00:36:48.150
the Yale Cancer

NOTE Confidence: 0.943004

00:36:48.710 --> 00:36:50.309
Center. The, the trials that

NOTE Confidence: 0.943004

00:36:50.309 --> 00:36:51.349
we have tend to turn

NOTE Confidence: 0.943004

00:36:51.349 --> 00:36:53.109
over over time. So, specific

NOTE Confidence: 0.943004

00:36:53.109 --> 00:36:54.869
trials, you know, kind of

NOTE Confidence: 0.943004

00:36:54.869 --> 00:36:55.750
come and go and we

NOTE Confidence: 0.943004

00:36:55.750 --> 00:36:56.710
open new ones and we

NOTE Confidence: 0.943004

00:36:56.710 --> 00:36:57.210
close.

NOTE Confidence: 0.9598969

00:36:57.750 --> 00:36:58.250
But,

NOTE Confidence: 0.9968647

00:36:58.630 --> 00:36:59.750
to think about some of

NOTE Confidence: 0.9968647

00:36:59.750 --> 00:37:00.809
the common questions,

NOTE Confidence: 0.93754095

00:37:01.750 --> 00:37:02.950
or the themes in the

NOTE Confidence: 0.93754095

00:37:02.950 --> 00:37:03.855
questions that,

NOTE Confidence: 0.97863144

00:37:04.734 --> 00:37:06.335
that are really at top

NOTE Confidence: 0.97863144

00:37:06.335 --> 00:37:07.395
of mind right now.

NOTE Confidence: 0.93685186

00:37:08.734 --> 00:37:09.935
So, one, you know, kind

NOTE Confidence: 0.93685186

00:37:09.935 --> 00:37:11.215
of common theme of the

NOTE Confidence: 0.93685186

00:37:11.215 --> 00:37:12.435
questions being asked

NOTE Confidence: 0.94659925

00:37:12.975 --> 00:37:13.695
by the, by trials for

NOTE Confidence: 0.94659925

00:37:13.695 --> 00:37:15.455
hormone receptor positive breast cancer

NOTE Confidence: 0.94659925

00:37:15.455 --> 00:37:16.655
is with all of these

NOTE Confidence: 0.94659925

00:37:16.655 --> 00:37:17.730
new drugs, are there ways

NOTE Confidence: 0.94659925

00:37:17.730 --> 00:37:19.250
that we can combine them,

NOTE Confidence: 0.94659925

00:37:19.489 --> 00:37:19.989
into,

NOTE Confidence: 0.85798454

00:37:20.530 --> 00:37:21.190
you know,

NOTE Confidence: 0.99078774

00:37:21.969 --> 00:37:22.870
larger combinations

NOTE Confidence: 0.89552754

00:37:23.250 --> 00:37:25.350
and get better results, for

NOTE Confidence: 0.89552754

00:37:25.570 --> 00:37:26.469
cancer patients?

NOTE Confidence: 0.97111297

00:37:27.170 --> 00:37:28.130
So, for instance, we have

NOTE Confidence: 0.97111297

00:37:28.130 --> 00:37:29.170
a trial right now that

NOTE Confidence: 0.97111297

00:37:29.170 --> 00:37:30.205
combines cabivacertib

NOTE Confidence: 0.7928884

00:37:30.585 --> 00:37:32.905
that, AKT pathway inhibitor, the

NOTE Confidence: 0.7928884

00:37:32.905 --> 00:37:33.805
true cap medication

NOTE Confidence: 0.70968986

00:37:34.344 --> 00:37:35.165
with a CDK4six

NOTE Confidence: 0.98263377

00:37:35.545 --> 00:37:36.045
inhibitor

NOTE Confidence: 0.97330993

00:37:36.425 --> 00:37:37.945
and with fulvestrant. And this

NOTE Confidence: 0.97330993

00:37:37.945 --> 00:37:38.985
is a trial that's looking

NOTE Confidence: 0.97330993

00:37:38.985 --> 00:37:39.864
at women who have the

NOTE Confidence: 0.97330993

00:37:39.864 --> 00:37:41.465
targeted mutations and women who

NOTE Confidence: 0.97330993

00:37:41.465 --> 00:37:42.505
might not have the targeted

NOTE Confidence: 0.97330993

00:37:42.505 --> 00:37:43.005
mutations.

NOTE Confidence: 0.97662747

00:37:44.120 --> 00:37:45.160
Another type of question we're

NOTE Confidence: 0.97662747

00:37:45.160 --> 00:37:46.440
asking is, are there,

NOTE Confidence: 0.9696938

00:37:47.080 --> 00:37:48.280
novel ways that we can,

NOTE Confidence: 0.991111

00:37:48.920 --> 00:37:50.760
administer these medications that,

NOTE Confidence: 0.916545

00:37:51.160 --> 00:37:53.000
that reduces side effects, reduces

NOTE Confidence: 0.916545

00:37:53.000 --> 00:37:53.500
toxicity.

NOTE Confidence: 0.97282094

00:37:54.040 --> 00:37:55.239
So, for instance, we have

NOTE Confidence: 0.97282094

00:37:55.239 --> 00:37:56.920
a trial, for older women,

NOTE Confidence: 0.97282094

00:37:56.920 --> 00:37:58.200
women over the age of

NOTE Confidence: 0.97282094

00:37:58.200 --> 00:37:59.955
sixty five looking at whether

NOTE Confidence: 0.97282094

00:37:59.955 --> 00:38:00.915
or not we can give

NOTE Confidence: 0.97282094

00:38:00.915 --> 00:38:02.455
the CDK four six inhibitors,

NOTE Confidence: 0.9963881

00:38:02.915 --> 00:38:04.295
in the first line setting,

NOTE Confidence: 0.9800056

00:38:04.835 --> 00:38:05.955
starting at a low dose

NOTE Confidence: 0.9800056

00:38:05.955 --> 00:38:07.155
and going up rather than

NOTE Confidence: 0.9800056

00:38:07.155 --> 00:38:08.195
starting at the highest dose

NOTE Confidence: 0.9800056

00:38:08.195 --> 00:38:09.395
that we offer and going

NOTE Confidence: 0.9800056

00:38:09.395 --> 00:38:10.755
down if they if if

NOTE Confidence: 0.9800056

00:38:10.755 --> 00:38:11.795
the dose is too high

NOTE Confidence: 0.9800056

00:38:11.795 --> 00:38:12.375
for them.

NOTE Confidence: 0.94170004

00:38:13.359 --> 00:38:14.480
And then, of course, we

NOTE Confidence: 0.94170004

00:38:14.480 --> 00:38:15.599
we all there's always new

NOTE Confidence: 0.94170004

00:38:15.599 --> 00:38:16.099
drugs.

NOTE Confidence: 0.9666389

00:38:16.880 --> 00:38:17.920
And so, we have novel

NOTE Confidence: 0.9666389

00:38:17.920 --> 00:38:19.359
drug trials, too.

NOTE Confidence: 0.9907527

00:38:19.680 --> 00:38:20.980
An example is,

NOTE Confidence: 0.9247576

00:38:21.280 --> 00:38:22.800
this drug, which doesn't even

NOTE Confidence: 0.9247576

00:38:22.800 --> 00:38:23.839
have a kind of scientific

NOTE Confidence: 0.9247576

00:38:23.839 --> 00:38:24.800
name yet but still sort

NOTE Confidence: 0.9247576

00:38:24.800 --> 00:38:26.020
of an industry shorthand.

NOTE Confidence: 0.9533197

00:38:27.405 --> 00:38:28.405
Relay two thousand six hundred

NOTE Confidence: 0.9533197

00:38:28.405 --> 00:38:29.805
and eight, which is a

NOTE Confidence: 0.9533197

00:38:29.805 --> 00:38:30.305
selective

NOTE Confidence: 0.86754465

00:38:30.765 --> 00:38:32.145
PI3 kinase inhibitor.

NOTE Confidence: 0.89500743

00:38:32.765 --> 00:38:33.665
And a selective,

NOTE Confidence: 0.9353676

00:38:34.525 --> 00:38:36.125
adjective sort of refers to

NOTE Confidence: 0.9353676

00:38:36.125 --> 00:38:37.645
its potential to maybe have

NOTE Confidence: 0.9353676

00:38:37.645 --> 00:38:39.485
fewer off target effects. And

NOTE Confidence: 0.9353676

00:38:39.485 --> 00:38:40.925
those off target effects are

NOTE Confidence: 0.9353676

00:38:40.925 --> 00:38:41.940
what cause toxicity.

NOTE Confidence: 0.9419361

00:38:44.260 --> 00:38:45.619
Toxicity than than some of

NOTE Confidence: 0.9419361

00:38:45.619 --> 00:38:46.900
the existing drugs in this

NOTE Confidence: 0.9419361

00:38:46.900 --> 00:38:47.400
class.

NOTE Confidence: 0.9487419

00:38:48.739 --> 00:38:49.859
So, I think I'll I'll

NOTE Confidence: 0.9487419

00:38:49.859 --> 00:38:50.660
stop there,

NOTE Confidence: 0.9922919

00:38:51.060 --> 00:38:51.560
and,

NOTE Confidence: 0.93285966

00:38:52.020 --> 00:38:52.980
we could we could open

NOTE Confidence: 0.93285966

00:38:52.980 --> 00:38:53.800
it up for questions.

NOTE Confidence: 0.9636136

00:38:57.625 --> 00:38:58.745
And maybe I'll I'll stop

NOTE Confidence: 0.9636136

00:38:58.745 --> 00:38:59.785
sharing too. You don't have

NOTE Confidence: 0.9636136

00:38:59.785 --> 00:39:00.425
to look at a black

NOTE Confidence: 0.9636136

00:39:00.425 --> 00:39:00.925
screen.

NOTE Confidence: 0.8341494

00:39:01.864 --> 00:39:02.685
Yeah. Dan,

NOTE Confidence: 0.99387366

00:39:03.225 --> 00:39:04.364
the question that,

NOTE Confidence: 0.8567834

00:39:05.225 --> 00:39:07.225
on Hartoulo disease and kind

NOTE Confidence: 0.8567834

00:39:07.225 --> 00:39:07.545
of,

NOTE Confidence: 0.981779

00:39:08.105 --> 00:39:09.625
you can see it in

NOTE Confidence: 0.981779

00:39:09.625 --> 00:39:11.320
the q and a. It

NOTE Confidence: 0.981779

00:39:11.320 --> 00:39:12.680
may come up as answered,

NOTE Confidence: 0.981779

00:39:12.680 --> 00:39:13.180
but

NOTE Confidence: 0.96946144

00:39:13.480 --> 00:39:14.520
I think it's the question

NOTE Confidence: 0.96946144

00:39:14.520 --> 00:39:15.020
that

NOTE Confidence: 0.9930393

00:39:15.719 --> 00:39:16.920
is a wonderful one in

NOTE Confidence: 0.9930393

00:39:16.920 --> 00:39:17.420
terms

NOTE Confidence: 0.98166436

00:39:17.800 --> 00:39:18.920
of what to do in

NOTE Confidence: 0.98166436

00:39:18.920 --> 00:39:20.940
the setting of HER2 low

NOTE Confidence: 0.98166436

00:39:21.080 --> 00:39:23.260
hormone receptor positive breast cancer

NOTE Confidence: 0.9942643

00:39:23.815 --> 00:39:25.355
and how you're envisioning,

NOTE Confidence: 0.9972489

00:39:26.375 --> 00:39:27.114
kind of

NOTE Confidence: 0.9795884

00:39:27.495 --> 00:39:29.355
the sequencing of HER2 ADCs

NOTE Confidence: 0.98724365

00:39:29.895 --> 00:39:30.875
in this setting,

NOTE Confidence: 0.9875678

00:39:31.735 --> 00:39:33.815
kind of earlier versus later.

NOTE Confidence: 0.9875678

00:39:33.815 --> 00:39:34.695
So if you could share

NOTE Confidence: 0.9875678

00:39:34.695 --> 00:39:35.915
your thoughts on that.

NOTE Confidence: 0.9992077

00:39:36.420 --> 00:39:37.719
Yeah. Yeah. Absolutely.

NOTE Confidence: 0.9964689

00:39:38.099 --> 00:39:38.819
You know, this is a

NOTE Confidence: 0.9964689

00:39:38.819 --> 00:39:40.579
question that actually applies to

NOTE Confidence: 0.9964689

00:39:40.579 --> 00:39:41.079
both,

NOTE Confidence: 0.9330186

00:39:41.780 --> 00:39:42.819
the types of breast cancer

NOTE Confidence: 0.9330186

00:39:42.819 --> 00:39:44.579
that, doctor Shalhoren and I

NOTE Confidence: 0.9330186

00:39:44.579 --> 00:39:46.660
spoke about. So HER2 low

NOTE Confidence: 0.9330186

00:39:46.660 --> 00:39:47.940
is sort of a newer

NOTE Confidence: 0.9330186

00:39:47.940 --> 00:39:48.440
idea,

NOTE Confidence: 0.9532399

00:39:49.380 --> 00:39:50.420
in in the breast cancer

NOTE Confidence: 0.9532399

00:39:50.420 --> 00:39:51.460
space or almost like a

NOTE Confidence: 0.9532399

00:39:51.460 --> 00:39:52.119
new classification

NOTE Confidence: 0.7089524

00:39:55.355 --> 00:39:55.855
three

NOTE Confidence: 0.899337

00:39:56.155 --> 00:39:57.114
buckets that that we've been

NOTE Confidence: 0.899337

00:39:57.114 --> 00:39:58.395
talking about is is sort

NOTE Confidence: 0.899337

00:39:58.395 --> 00:39:59.594
of how we classically thought

NOTE Confidence: 0.899337

00:39:59.594 --> 00:40:00.815
about breast cancer subtypes.

NOTE Confidence: 0.86944264

00:40:01.355 --> 00:40:02.395
But I I think in

NOTE Confidence: 0.86944264

00:40:02.395 --> 00:40:04.155
doctor Schallhorn's slide describing what

NOTE Confidence: 0.86944264

00:40:04.155 --> 00:40:05.775
HER2 HER2 is,

NOTE Confidence: 0.9726453

00:40:06.155 --> 00:40:06.955
you could see on that

NOTE Confidence: 0.9726453

00:40:06.955 --> 00:40:07.455
normal,

NOTE Confidence: 0.9853162

00:40:07.915 --> 00:40:09.089
cell that there was still

NOTE Confidence: 0.9853162

00:40:09.089 --> 00:40:11.329
HER2 protein. Like, it's when

NOTE Confidence: 0.9853162

00:40:11.329 --> 00:40:12.529
we talk about HER2 negative

NOTE Confidence: 0.9853162

00:40:12.529 --> 00:40:13.650
cancers, that doesn't mean there's

NOTE Confidence: 0.9853162

00:40:13.650 --> 00:40:14.630
no HER2 protein.

NOTE Confidence: 0.9392489

00:40:15.250 --> 00:40:16.930
So so HER2 low breast

NOTE Confidence: 0.9392489

00:40:16.930 --> 00:40:18.769
cancers refer to HER2 or

NOTE Confidence: 0.9392489

00:40:18.769 --> 00:40:20.049
breast cancers that have some

NOTE Confidence: 0.9392489

00:40:20.049 --> 00:40:21.589
HER2 protein, but not necessarily

NOTE Confidence: 0.9392489

00:40:21.730 --> 00:40:23.555
this over expressed amount. This,

NOTE Confidence: 0.9392489

00:40:23.555 --> 00:40:25.475
like, extra HER2 protein that,

NOTE Confidence: 0.97108316

00:40:26.115 --> 00:40:26.595
that,

NOTE Confidence: 0.9894292

00:40:26.995 --> 00:40:28.615
has typically made those cancers,

NOTE Confidence: 0.99704033

00:40:29.315 --> 00:40:30.995
more sensitive to the anti

NOTE Confidence: 0.99704033

00:40:30.995 --> 00:40:31.895
HER2 drugs.

NOTE Confidence: 0.970939

00:40:33.315 --> 00:40:34.835
Why that's an important distinction

NOTE Confidence: 0.970939

00:40:34.835 --> 00:40:35.555
to make now, why it's

NOTE Confidence: 0.970939

00:40:35.555 --> 00:40:37.235
important to identify cancers that

NOTE Confidence: 0.970939

00:40:37.235 --> 00:40:38.860
have some but not too

NOTE Confidence: 0.970939

00:40:38.860 --> 00:40:40.000
much HER2 protein

NOTE Confidence: 0.8774765

00:40:40.380 --> 00:40:41.900
is because one drug in

NOTE Confidence: 0.8774765

00:40:41.900 --> 00:40:43.180
particular so far and then

NOTE Confidence: 0.8774765

00:40:43.180 --> 00:40:44.380
surely more in the future.

NOTE Confidence: 0.8774765

00:40:44.380 --> 00:40:46.400
One one particular drug, the,

NOTE Confidence: 0.71158206

00:40:46.700 --> 00:40:47.920
trastuzumab, drexatecan,

NOTE Confidence: 0.9392456

00:40:48.300 --> 00:40:49.580
the HER2 drug that,

NOTE Confidence: 0.92430806

00:40:50.105 --> 00:40:51.484
that Doctor. Shellhorn talked

NOTE Confidence: 0.94990426

00:40:51.864 --> 00:40:53.464
about, is actually effective not

NOTE Confidence: 0.94990426

00:40:53.464 --> 00:40:55.805
only in classically HER2 positive,

NOTE Confidence: 0.9189496

00:40:56.184 --> 00:40:57.545
breast cancer, but is also

NOTE Confidence: 0.9189496

00:40:57.545 --> 00:40:58.045
effective

NOTE Confidence: 0.99194926

00:40:58.424 --> 00:40:59.325
in HER2

NOTE Confidence: 0.99013823

00:40:59.704 --> 00:41:00.765
low breast cancer.

NOTE Confidence: 0.9040865

00:41:01.145 --> 00:41:02.585
So, if you're hormone receptor

NOTE Confidence: 0.9040865

00:41:02.585 --> 00:41:04.469
positive, HER2 negative, but HER2

NOTE Confidence: 0.9040865

00:41:04.469 --> 00:41:06.150
low, then HER2 can be

NOTE Confidence: 0.9040865

00:41:06.150 --> 00:41:07.450
it can be very effective.

NOTE Confidence: 0.9040865

00:41:07.670 --> 00:41:08.950
If you're a triple negative

NOTE Confidence: 0.9040865

00:41:08.950 --> 00:41:10.010
but HER2 low,

NOTE Confidence: 0.8938238

00:41:10.390 --> 00:41:11.910
that that, and HER2 can

NOTE Confidence: 0.8938238

00:41:11.910 --> 00:41:12.810
be very effective.

NOTE Confidence: 0.98964727

00:41:13.430 --> 00:41:14.390
And so we've been we've

NOTE Confidence: 0.98964727

00:41:14.390 --> 00:41:15.590
been using that drug for

NOTE Confidence: 0.98964727

00:41:15.590 --> 00:41:16.790
several years now for those

NOTE Confidence: 0.98964727

00:41:16.790 --> 00:41:17.989
types of breast cancers as

NOTE Confidence: 0.98964727

00:41:17.989 --> 00:41:18.489
well.

NOTE Confidence: 0.9825808

00:41:19.035 --> 00:41:20.415
In in terms of sequencing,

NOTE Confidence: 0.99658346

00:41:22.075 --> 00:41:22.895
the the

NOTE Confidence: 0.968923

00:41:23.275 --> 00:41:23.775
the,

NOTE Confidence: 0.9249665

00:41:26.155 --> 00:41:27.755
standard, I would say, is

NOTE Confidence: 0.9249665

00:41:27.755 --> 00:41:28.255
still

NOTE Confidence: 0.97321916

00:41:28.555 --> 00:41:30.155
for hormone receptor positive breast

NOTE Confidence: 0.97321916

00:41:30.155 --> 00:41:31.869
cancer is is to really

NOTE Confidence: 0.97321916

00:41:31.869 --> 00:41:32.989
make the most of the

NOTE Confidence: 0.97321916

00:41:32.989 --> 00:41:34.210
anti estrogen therapies.

NOTE Confidence: 0.9685955

00:41:34.590 --> 00:41:36.030
Those cancers are still most

NOTE Confidence: 0.9685955

00:41:36.030 --> 00:41:37.790
sensitive to anti estrogen approaches,

NOTE Confidence: 0.9685955

00:41:37.790 --> 00:41:39.250
like the anti estrogen medicines

NOTE Confidence: 0.9623695

00:41:39.550 --> 00:41:41.150
work best and and longest,

NOTE Confidence: 0.9623695

00:41:41.390 --> 00:41:42.989
for hormone receptor positive breast

NOTE Confidence: 0.9623695

00:41:42.989 --> 00:41:43.489
cancers,

NOTE Confidence: 0.99735725

00:41:44.190 --> 00:41:45.090
early on.

NOTE Confidence: 0.9440182

00:41:45.625 --> 00:41:47.225
They tend to have fewer

NOTE Confidence: 0.9440182

00:41:47.225 --> 00:41:47.885
side effects.

NOTE Confidence: 0.8036951

00:41:48.745 --> 00:41:49.245
Well,

NOTE Confidence: 0.8906987

00:41:50.905 --> 00:41:52.105
experiences can be mixed, actually.

NOTE Confidence: 0.8906987

00:41:52.105 --> 00:41:52.905
I don't want to say

NOTE Confidence: 0.8906987

00:41:52.905 --> 00:41:53.965
that HER2 has

NOTE Confidence: 0.91910493

00:41:54.265 --> 00:41:55.065
a lot of side effects

NOTE Confidence: 0.91910493

00:41:55.065 --> 00:41:56.825
for everyone, or that the

NOTE Confidence: 0.91910493

00:41:56.825 --> 00:41:58.505
antihistamine medications don't have side

NOTE Confidence: 0.91910493

00:41:58.505 --> 00:41:59.725
effects. It can be significant.

NOTE Confidence: 0.9067902

00:42:00.950 --> 00:42:02.630
But oftentimes they have fewer

NOTE Confidence: 0.9067902

00:42:02.630 --> 00:42:03.369
side effects,

NOTE Confidence: 0.87336046

00:42:03.989 --> 00:42:04.489
than,

NOTE Confidence: 0.90314215

00:42:05.349 --> 00:42:06.710
the inher tube medication. So,

NOTE Confidence: 0.90314215

00:42:06.710 --> 00:42:08.230
we still try to use

NOTE Confidence: 0.90314215

00:42:08.230 --> 00:42:10.390
as many, antiastrogen medications as

NOTE Confidence: 0.90314215

00:42:10.390 --> 00:42:10.890
possible,

NOTE Confidence: 0.93121123

00:42:12.230 --> 00:42:14.010
before changing to infusional

NOTE Confidence: 0.91682553

00:42:14.789 --> 00:42:16.825
chemotherapy based medications. Medications.

NOTE Confidence: 0.99872375

00:42:17.285 --> 00:42:18.025
And then

NOTE Confidence: 0.95605564

00:42:18.485 --> 00:42:20.085
there is some, you know,

NOTE Confidence: 0.95605564

00:42:20.085 --> 00:42:21.845
some recent conversation about whether

NOTE Confidence: 0.95605564

00:42:21.845 --> 00:42:23.045
HER2 should be the very

NOTE Confidence: 0.95605564

00:42:23.045 --> 00:42:24.245
first drug that we use

NOTE Confidence: 0.95605564

00:42:24.245 --> 00:42:26.405
after anti estrogen medication or

NOTE Confidence: 0.95605564

00:42:26.405 --> 00:42:26.885
if,

NOTE Confidence: 0.9891959

00:42:27.445 --> 00:42:28.185
if chemotherapies

NOTE Confidence: 0.75077355

00:42:28.645 --> 00:42:29.145
can,

NOTE Confidence: 0.9079577

00:42:30.430 --> 00:42:32.030
still, you know, if a

NOTE Confidence: 0.9079577

00:42:32.030 --> 00:42:33.469
chemotherapy before moving to an

NOTE Confidence: 0.9079577

00:42:33.469 --> 00:42:34.530
HER2 is appropriate.

NOTE Confidence: 0.9685577

00:42:35.230 --> 00:42:36.590
And that conversation is really

NOTE Confidence: 0.9685577

00:42:36.590 --> 00:42:37.730
based on balancing

NOTE Confidence: 0.9824836

00:42:38.510 --> 00:42:40.210
length of response versus,

NOTE Confidence: 0.9134959

00:42:41.390 --> 00:42:41.890
versus,

NOTE Confidence: 0.99154025

00:42:42.350 --> 00:42:43.090
side effects

NOTE Confidence: 0.93923414

00:42:43.469 --> 00:42:44.510
and whether or not a

NOTE Confidence: 0.93923414

00:42:44.510 --> 00:42:45.954
drug that might control the

NOTE Confidence: 0.93923414

00:42:45.954 --> 00:42:47.234
cancer longer but have more

NOTE Confidence: 0.93923414

00:42:47.234 --> 00:42:47.974
side effects,

NOTE Confidence: 0.9848687

00:42:48.355 --> 00:42:49.075
whether or not you could

NOTE Confidence: 0.9848687

00:42:49.075 --> 00:42:49.954
kind of get the same

NOTE Confidence: 0.9848687

00:42:49.954 --> 00:42:51.875
effect by by turning to

NOTE Confidence: 0.9848687

00:42:51.875 --> 00:42:52.835
that drug a little bit

NOTE Confidence: 0.9848687

00:42:52.835 --> 00:42:53.335
later.

NOTE Confidence: 0.9951451

00:42:54.515 --> 00:42:55.015
So,

NOTE Confidence: 0.9505722

00:42:55.315 --> 00:42:56.994
it's, it's an exciting space.

NOTE Confidence: 0.9505722

00:42:56.994 --> 00:42:58.114
I mean and and and

NOTE Confidence: 0.9505722

00:42:58.114 --> 00:42:58.915
it's a space where I

NOTE Confidence: 0.9505722

00:42:58.915 --> 00:42:59.875
think there there will be

NOTE Confidence: 0.9505722

00:42:59.875 --> 00:43:00.915
a lot of new medications

NOTE Confidence: 0.9505722

00:43:00.915 --> 00:43:01.850
over the over over the

NOTE Confidence: 0.9505722

00:43:01.850 --> 00:43:02.510
coming years.

NOTE Confidence: 0.9831495

00:43:03.530 --> 00:43:04.489
And I think for the

NOTE Confidence: 0.9831495

00:43:04.489 --> 00:43:06.110
listeners, this is your opportunity

NOTE Confidence: 0.9831495

00:43:06.330 --> 00:43:08.350
when these junctures are occurring

NOTE Confidence: 0.9831495

00:43:08.410 --> 00:43:09.310
in your care

NOTE Confidence: 0.9680732

00:43:09.770 --> 00:43:11.310
to be asking your oncologist,

NOTE Confidence: 0.9712655

00:43:11.610 --> 00:43:12.890
what are my options? What

NOTE Confidence: 0.9712655

00:43:12.890 --> 00:43:14.340
are my alternatives? And,

NOTE Confidence: 0.9970403

00:43:15.085 --> 00:43:15.725
I think,

NOTE Confidence: 0.999815

00:43:16.125 --> 00:43:17.805
what we all aim for

NOTE Confidence: 0.999815

00:43:17.805 --> 00:43:18.545
is to

NOTE Confidence: 0.99954706

00:43:19.085 --> 00:43:19.585
summarize

NOTE Confidence: 0.94730616

00:43:20.525 --> 00:43:22.445
currently, as as my colleague

NOTE Confidence: 0.94730616

00:43:22.445 --> 00:43:23.565
just mentioned, there are so

NOTE Confidence: 0.94730616

00:43:23.565 --> 00:43:25.085
many options for each line

NOTE Confidence: 0.94730616

00:43:25.085 --> 00:43:26.545
of therapy in breast cancer.

NOTE Confidence: 0.99176633

00:43:27.005 --> 00:43:28.450
So a lot will come

NOTE Confidence: 0.99176633

00:43:28.450 --> 00:43:30.870
down to patients actively deciding

NOTE Confidence: 0.99176633

00:43:30.930 --> 00:43:31.910
with their oncologist

NOTE Confidence: 0.98835987

00:43:32.610 --> 00:43:34.550
based on preferences of schedule,

NOTE Confidence: 0.98835987

00:43:34.770 --> 00:43:36.450
side effects, and so many

NOTE Confidence: 0.98835987

00:43:36.450 --> 00:43:38.210
other considerations. So don't be

NOTE Confidence: 0.98835987

00:43:38.210 --> 00:43:38.710
afraid

NOTE Confidence: 0.9994901

00:43:39.170 --> 00:43:40.610
to be bringing up these

NOTE Confidence: 0.9994901

00:43:40.610 --> 00:43:41.110
questions.

NOTE Confidence: 0.99454457

00:43:41.489 --> 00:43:42.370
We we would love to

NOTE Confidence: 0.99454457

00:43:42.370 --> 00:43:43.270
have these conversations.

NOTE Confidence: 0.97018284

00:43:44.605 --> 00:43:45.485
There is a there was

NOTE Confidence: 0.97018284

00:43:45.485 --> 00:43:46.685
a question in the chat

NOTE Confidence: 0.97018284

00:43:46.685 --> 00:43:48.364
that's also an excellent one

NOTE Confidence: 0.97018284

00:43:48.364 --> 00:43:49.265
in terms of

NOTE Confidence: 0.9965958

00:43:49.565 --> 00:43:50.625
when we test,

NOTE Confidence: 0.9622555

00:43:51.325 --> 00:43:53.825
for these different, targetable pathways.

NOTE Confidence: 0.9622555

00:43:53.885 --> 00:43:55.485
So doctor Shellhorn will answer

NOTE Confidence: 0.9622555

00:43:55.485 --> 00:43:57.359
that live. Yeah. No. It

NOTE Confidence: 0.9622555

00:43:57.440 --> 00:43:58.480
it's a it's a great

NOTE Confidence: 0.9622555

00:43:58.480 --> 00:43:59.940
question, and doctor O'Neil

NOTE Confidence: 0.99940354

00:44:00.319 --> 00:44:02.339
talked a lot about targetable

NOTE Confidence: 0.99940354

00:44:02.400 --> 00:44:02.900
mutations.

NOTE Confidence: 0.97613245

00:44:04.480 --> 00:44:06.559
It it's applicable for any

NOTE Confidence: 0.97613245

00:44:06.559 --> 00:44:07.680
type of breast cancer, at

NOTE Confidence: 0.97613245

00:44:07.680 --> 00:44:08.799
least to some degree. It's

NOTE Confidence: 0.97613245

00:44:08.799 --> 00:44:10.880
particularly relevant for cancers that

NOTE Confidence: 0.97613245

00:44:10.880 --> 00:44:12.105
are driven by hormones. So

NOTE Confidence: 0.97613245

00:44:12.105 --> 00:44:13.705
the hormone receptor positive breast

NOTE Confidence: 0.97613245

00:44:13.705 --> 00:44:14.205
cancers.

NOTE Confidence: 0.9373985

00:44:15.864 --> 00:44:17.244
Doctor O'Neil mentioned

NOTE Confidence: 0.9086123

00:44:17.625 --> 00:44:18.125
specifically

NOTE Confidence: 0.9782238

00:44:18.425 --> 00:44:19.485
ESR one,

NOTE Confidence: 0.91218585

00:44:20.505 --> 00:44:22.105
looking at anything in the

NOTE Confidence: 0.91218585

00:44:22.105 --> 00:44:23.864
AKT pathway. So AKT p

NOTE Confidence: 0.91218585

00:44:23.864 --> 00:44:25.005
ten PI three kinase,

NOTE Confidence: 0.7843256

00:44:25.545 --> 00:44:26.525
PIK three CA,

NOTE Confidence: 0.97457546

00:44:27.350 --> 00:44:28.230
as well as a few

NOTE Confidence: 0.97457546

00:44:28.230 --> 00:44:29.930
other mutations that have

NOTE Confidence: 0.9993038

00:44:30.550 --> 00:44:32.010
that are that are considered

NOTE Confidence: 0.9648733

00:44:32.390 --> 00:44:34.550
druggable. Meaning, we have drugs

NOTE Confidence: 0.9648733

00:44:34.550 --> 00:44:35.450
that that

NOTE Confidence: 0.9471949

00:44:36.150 --> 00:44:38.469
focus on those molecular engine

NOTE Confidence: 0.9471949

00:44:38.790 --> 00:44:39.850
genomic abnormalities

NOTE Confidence: 0.99259144

00:44:40.150 --> 00:44:41.830
and and help kind of

NOTE Confidence: 0.99259144

00:44:41.830 --> 00:44:43.635
turn off the switches that

NOTE Confidence: 0.99259144

00:44:43.635 --> 00:44:44.935
might be driving the cancer.

NOTE Confidence: 0.9975986

00:44:45.795 --> 00:44:46.614
And so

NOTE Confidence: 0.99485147

00:44:48.195 --> 00:44:50.195
there's no right answer or

NOTE Confidence: 0.99485147

00:44:50.195 --> 00:44:51.715
wrong answer to how often

NOTE Confidence: 0.99485147

00:44:51.715 --> 00:44:52.614
to be testing.

NOTE Confidence: 0.9716043

00:44:54.355 --> 00:44:55.395
And I think kind of

NOTE Confidence: 0.9716043

00:44:55.395 --> 00:44:57.075
a a a corollary to

NOTE Confidence: 0.9716043

00:44:57.075 --> 00:44:58.530
this is how to test

NOTE Confidence: 0.9716043

00:44:58.530 --> 00:44:59.410
because there are a couple

NOTE Confidence: 0.9716043

00:44:59.410 --> 00:45:00.210
of ways that you can

NOTE Confidence: 0.9716043

00:45:00.210 --> 00:45:01.969
test for genomic abnormalities. You

NOTE Confidence: 0.9716043

00:45:01.969 --> 00:45:03.430
can test the cancer itself

NOTE Confidence: 0.99727243

00:45:03.810 --> 00:45:05.030
on a biopsy specimen.

NOTE Confidence: 0.99397504

00:45:05.570 --> 00:45:06.870
So you if you have

NOTE Confidence: 0.99397504

00:45:06.930 --> 00:45:07.969
a cancer that's got a

NOTE Confidence: 0.99397504

00:45:07.969 --> 00:45:09.489
deposit in the liver, for

NOTE Confidence: 0.99397504

00:45:09.489 --> 00:45:09.989
example,

NOTE Confidence: 0.9900385

00:45:10.450 --> 00:45:11.570
you could get a liver

NOTE Confidence: 0.9900385

00:45:11.570 --> 00:45:13.090
biopsy to take a sample

NOTE Confidence: 0.9900385

00:45:13.090 --> 00:45:14.445
of that particular tissue and

NOTE Confidence: 0.9900385

00:45:14.445 --> 00:45:15.485
then send it to the

NOTE Confidence: 0.9900385

00:45:15.485 --> 00:45:16.445
to the lab to look

NOTE Confidence: 0.9900385

00:45:16.445 --> 00:45:17.805
at under the microscope where

NOTE Confidence: 0.9900385

00:45:17.805 --> 00:45:19.165
we would test for estrogen

NOTE Confidence: 0.9900385

00:45:19.165 --> 00:45:21.085
receptor, progesterone receptor, HER2, and

NOTE Confidence: 0.9900385

00:45:21.085 --> 00:45:22.125
we could also then send

NOTE Confidence: 0.9900385

00:45:22.125 --> 00:45:23.565
it for all of these

NOTE Confidence: 0.9900385

00:45:23.565 --> 00:45:25.245
molecular tests to look for

NOTE Confidence: 0.9900385

00:45:25.245 --> 00:45:26.945
any sort of genomic abnormality.

NOTE Confidence: 0.97958696

00:45:29.550 --> 00:45:30.770
But you can also

NOTE Confidence: 0.98203635

00:45:31.310 --> 00:45:32.989
do what we call a

NOTE Confidence: 0.98203635

00:45:32.989 --> 00:45:34.670
liquid biopsy, which is a

NOTE Confidence: 0.98203635

00:45:34.670 --> 00:45:35.410
blood test,

NOTE Confidence: 0.9997401

00:45:35.790 --> 00:45:36.930
looking at

NOTE Confidence: 0.99166775

00:45:37.630 --> 00:45:39.550
DNA from the cancer that

NOTE Confidence: 0.99166775

00:45:39.550 --> 00:45:40.830
might be circulating in the

NOTE Confidence: 0.99166775

00:45:40.830 --> 00:45:42.494
blood and getting that same

NOTE Confidence: 0.99166775

00:45:42.494 --> 00:45:44.414
information in a much less

NOTE Confidence: 0.99166775

00:45:44.414 --> 00:45:46.015
invasive way. So it doesn't

NOTE Confidence: 0.99166775

00:45:46.015 --> 00:45:47.295
require a biopsy or a

NOTE Confidence: 0.99166775

00:45:47.295 --> 00:45:48.414
needle. It just requires a

NOTE Confidence: 0.99166775

00:45:48.414 --> 00:45:49.154
blood draw.

NOTE Confidence: 0.98686177

00:45:49.934 --> 00:45:51.555
And so with the advent

NOTE Confidence: 0.98686177

00:45:51.694 --> 00:45:53.795
of these liquid biopsies,

NOTE Confidence: 0.9928654

00:45:55.855 --> 00:45:56.914
the the opportunity

NOTE Confidence: 0.99893075

00:45:58.390 --> 00:46:00.170
is is much less risky

NOTE Confidence: 0.99939764

00:46:00.550 --> 00:46:02.170
and much easier to do

NOTE Confidence: 0.9976635

00:46:02.550 --> 00:46:04.150
at any point where it

NOTE Confidence: 0.9976635

00:46:04.150 --> 00:46:05.930
could theoretically change management.

NOTE Confidence: 0.9920158

00:46:06.469 --> 00:46:08.150
And so I think most

NOTE Confidence: 0.9920158

00:46:08.150 --> 00:46:10.070
of us are testing pretty

NOTE Confidence: 0.9920158

00:46:10.070 --> 00:46:10.969
early on,

NOTE Confidence: 0.8635784

00:46:12.315 --> 00:46:13.775
maybe not immediately

NOTE Confidence: 0.97239465

00:46:14.075 --> 00:46:15.855
after a diagnosis of metastatic

NOTE Confidence: 0.97239465

00:46:15.915 --> 00:46:17.035
breast cancer. But, again, it

NOTE Confidence: 0.97239465

00:46:17.035 --> 00:46:18.575
might depend on on

NOTE Confidence: 0.9770438

00:46:19.035 --> 00:46:20.494
what what a patient's,

NOTE Confidence: 0.96524245

00:46:20.875 --> 00:46:22.234
what a patient's story is,

NOTE Confidence: 0.96524245

00:46:22.234 --> 00:46:23.355
what their history is, had

NOTE Confidence: 0.96524245

00:46:23.355 --> 00:46:24.715
they gotten prior treatment, and

NOTE Confidence: 0.96524245

00:46:24.715 --> 00:46:25.915
if so, how long ago,

NOTE Confidence: 0.96524245

00:46:25.915 --> 00:46:27.160
and what medicines were they

NOTE Confidence: 0.96524245

00:46:27.160 --> 00:46:27.660
on?

NOTE Confidence: 0.9614673

00:46:28.840 --> 00:46:29.719
So you might test as

NOTE Confidence: 0.9614673

00:46:29.719 --> 00:46:30.920
early as right then and

NOTE Confidence: 0.9614673

00:46:30.920 --> 00:46:32.060
there at the first

NOTE Confidence: 0.98882514

00:46:32.440 --> 00:46:33.820
the first sign of metastatic

NOTE Confidence: 0.98882514

00:46:33.880 --> 00:46:34.380
disease.

NOTE Confidence: 0.9361013

00:46:36.040 --> 00:46:37.739
But I think for certain,

NOTE Confidence: 0.9566882

00:46:38.360 --> 00:46:40.280
after progression on first line

NOTE Confidence: 0.9566882

00:46:40.280 --> 00:46:42.364
therapy for hormone receptor positive

NOTE Confidence: 0.9566882

00:46:42.364 --> 00:46:44.145
breast cancer because that's when

NOTE Confidence: 0.9566882

00:46:44.364 --> 00:46:46.704
these molecular targets really become,

NOTE Confidence: 0.999123

00:46:48.285 --> 00:46:49.265
become relevant

NOTE Confidence: 0.99617004

00:46:49.565 --> 00:46:51.665
after progression on on

NOTE Confidence: 0.944118

00:46:52.204 --> 00:46:53.645
the first line, usually an

NOTE Confidence: 0.944118

00:46:53.645 --> 00:46:55.244
aromatase inhibitor and a CDK

NOTE Confidence: 0.944118

00:46:55.244 --> 00:46:56.850
four six inhibitor as doctor

NOTE Confidence: 0.944118

00:46:56.850 --> 00:46:57.830
O'Neil described.

NOTE Confidence: 0.9530724

00:46:59.730 --> 00:47:01.650
But then things can change

NOTE Confidence: 0.9530724

00:47:01.650 --> 00:47:02.930
over time and things can

NOTE Confidence: 0.9530724

00:47:02.930 --> 00:47:05.010
develop. So for example, that

NOTE Confidence: 0.9530724

00:47:05.010 --> 00:47:06.310
ESR one mutation

NOTE Confidence: 0.9578724

00:47:06.930 --> 00:47:07.989
ESR one mutation

NOTE Confidence: 0.96745235

00:47:08.930 --> 00:47:11.085
isn't usually very common right

NOTE Confidence: 0.96745235

00:47:11.085 --> 00:47:11.805
at the time of a

NOTE Confidence: 0.96745235

00:47:11.805 --> 00:47:13.965
metastatic diagnosis unless someone had

NOTE Confidence: 0.96745235

00:47:13.965 --> 00:47:14.705
been on,

NOTE Confidence: 0.9381734

00:47:15.565 --> 00:47:17.245
previous therapies. It but it

NOTE Confidence: 0.9381734

00:47:17.245 --> 00:47:17.905
can develop,

NOTE Confidence: 0.99259275

00:47:18.844 --> 00:47:20.364
in even up to forty,

NOTE Confidence: 0.99259275

00:47:20.364 --> 00:47:22.045
fifty percent of patients who

NOTE Confidence: 0.99259275

00:47:22.045 --> 00:47:23.790
have been on aromatase inhibitors

NOTE Confidence: 0.99259275

00:47:23.870 --> 00:47:25.710
over time. So we would

NOTE Confidence: 0.99259275

00:47:25.710 --> 00:47:26.210
check

NOTE Confidence: 0.994586

00:47:27.390 --> 00:47:27.890
periodically

NOTE Confidence: 0.93985254

00:47:28.350 --> 00:47:29.250
at the time

NOTE Confidence: 0.97846776

00:47:29.790 --> 00:47:30.989
that there's a a sense

NOTE Confidence: 0.97846776

00:47:30.989 --> 00:47:32.350
of the cancer starting to

NOTE Confidence: 0.97846776

00:47:32.350 --> 00:47:32.850
progress,

NOTE Confidence: 0.99903953

00:47:33.550 --> 00:47:36.030
check for for circulating tumor

NOTE Confidence: 0.99903953

00:47:36.030 --> 00:47:37.489
DNA, check for mutations

NOTE Confidence: 0.998584

00:47:38.195 --> 00:47:39.094
with the idea,

NOTE Confidence: 0.9991661

00:47:39.715 --> 00:47:41.094
that something targetable

NOTE Confidence: 0.9983885

00:47:41.395 --> 00:47:43.155
if something targetable were found,

NOTE Confidence: 0.9983885

00:47:43.155 --> 00:47:44.055
we could then

NOTE Confidence: 0.999261

00:47:44.675 --> 00:47:45.655
target it.

NOTE Confidence: 0.9985044

00:47:46.835 --> 00:47:47.875
And the other time to

NOTE Confidence: 0.9985044

00:47:47.875 --> 00:47:49.415
consider molecular testing

NOTE Confidence: 0.9993129

00:47:50.035 --> 00:47:50.535
is

NOTE Confidence: 0.9798526

00:47:51.480 --> 00:47:53.640
when considering clinical trials because

NOTE Confidence: 0.9798526

00:47:53.640 --> 00:47:55.239
there are new drugs becoming

NOTE Confidence: 0.9798526

00:47:55.239 --> 00:47:57.260
available for particular mutations,

NOTE Confidence: 0.99798316

00:47:58.040 --> 00:48:00.380
certain earlier phase clinical trials

NOTE Confidence: 0.9906886

00:48:00.920 --> 00:48:02.140
that are,

NOTE Confidence: 0.9888447

00:48:03.080 --> 00:48:05.020
applicable to patients with certain

NOTE Confidence: 0.90907943

00:48:08.785 --> 00:48:09.925
FDA approved

NOTE Confidence: 0.9522818

00:48:10.225 --> 00:48:10.725
targetable,

NOTE Confidence: 0.9912939

00:48:13.825 --> 00:48:15.925
druggable targets at this point.

NOTE Confidence: 0.9481476

00:48:17.265 --> 00:48:17.765
So

NOTE Confidence: 0.98987395

00:48:18.385 --> 00:48:19.985
lots of opportunities, and it's

NOTE Confidence: 0.98987395

00:48:19.985 --> 00:48:21.505
getting easier and easier to

NOTE Confidence: 0.98987395

00:48:21.505 --> 00:48:21.960
do.

NOTE Confidence: 0.99585134

00:48:23.320 --> 00:48:24.280
Kim, I hope that answers

NOTE Confidence: 0.99585134

00:48:24.280 --> 00:48:24.940
your question.

NOTE Confidence: 0.9658063

00:48:27.320 --> 00:48:28.839
Yes. And there was also

NOTE Confidence: 0.9658063

00:48:28.839 --> 00:48:30.520
an additional question about is

NOTE Confidence: 0.9658063

00:48:30.520 --> 00:48:32.040
ESR one testing ever done

NOTE Confidence: 0.9658063

00:48:32.040 --> 00:48:33.820
in early stage breast cancer.

NOTE Confidence: 0.99827623

00:48:34.200 --> 00:48:35.239
And I would say,

NOTE Confidence: 0.96278054

00:48:35.640 --> 00:48:37.400
one, two points there. These

NOTE Confidence: 0.96278054

00:48:37.400 --> 00:48:37.900
are

NOTE Confidence: 0.9983379

00:48:38.495 --> 00:48:40.355
acquired alterations that

NOTE Confidence: 0.99982923

00:48:40.735 --> 00:48:42.835
occur under selective pressure

NOTE Confidence: 0.99841404

00:48:43.614 --> 00:48:44.114
of

NOTE Confidence: 0.9538602

00:48:44.495 --> 00:48:46.575
more longer exposure to anti

NOTE Confidence: 0.9538602

00:48:46.575 --> 00:48:48.515
estrogen therapy. So you're unlikely

NOTE Confidence: 0.9538602

00:48:48.815 --> 00:48:49.775
you're gonna have a low

NOTE Confidence: 0.9538602

00:48:49.775 --> 00:48:51.135
chance of finding it early

NOTE Confidence: 0.9538602

00:48:51.135 --> 00:48:52.495
on in early stage breast

NOTE Confidence: 0.9538602

00:48:52.495 --> 00:48:52.995
cancer.

NOTE Confidence: 0.9996134

00:48:53.460 --> 00:48:55.480
However, there are studies investigating

NOTE Confidence: 0.9530355

00:48:56.020 --> 00:48:58.099
adjuvant SIRDS in high risk

NOTE Confidence: 0.9530355

00:48:58.099 --> 00:48:59.400
early stage breast cancer.

NOTE Confidence: 0.99315995

00:48:59.700 --> 00:49:01.219
So as often happens, if

NOTE Confidence: 0.99315995

00:49:01.219 --> 00:49:02.660
something is approved and shown

NOTE Confidence: 0.99315995

00:49:02.660 --> 00:49:04.280
to be effective in metastatic

NOTE Confidence: 0.99315995

00:49:04.340 --> 00:49:05.859
breast cancer, we do start

NOTE Confidence: 0.99315995

00:49:05.859 --> 00:49:07.140
testing it in early stage

NOTE Confidence: 0.99315995

00:49:07.140 --> 00:49:07.880
breast cancer.

NOTE Confidence: 0.96302253

00:49:08.945 --> 00:49:10.705
There are couple of questions

NOTE Confidence: 0.96302253

00:49:10.705 --> 00:49:12.325
in the chat that are

NOTE Confidence: 0.98184747

00:49:12.785 --> 00:49:14.225
are complex, so we might

NOTE Confidence: 0.98184747

00:49:14.225 --> 00:49:15.344
need to kind of tag

NOTE Confidence: 0.98184747

00:49:15.344 --> 00:49:16.005
team it.

NOTE Confidence: 0.78148997

00:49:17.265 --> 00:49:17.765
So,

NOTE Confidence: 0.9613436

00:49:20.945 --> 00:49:21.540
so let's,

NOTE Confidence: 0.973775

00:49:22.820 --> 00:49:24.260
let's take the question from

NOTE Confidence: 0.973775

00:49:24.260 --> 00:49:25.239
doctor Ward,

NOTE Confidence: 0.79544055

00:49:26.739 --> 00:49:27.239
on,

NOTE Confidence: 0.9707882

00:49:27.620 --> 00:49:29.219
will doctor Ward is one

NOTE Confidence: 0.9707882

00:49:29.219 --> 00:49:29.800
of our,

NOTE Confidence: 0.9767707

00:49:30.580 --> 00:49:31.880
amazing breast surgeons,

NOTE Confidence: 0.9045831

00:49:32.260 --> 00:49:34.120
within Yale network. So,

NOTE Confidence: 0.99139065

00:49:35.614 --> 00:49:36.575
so in the setting of

NOTE Confidence: 0.99139065

00:49:36.575 --> 00:49:37.075
oligometastatic

NOTE Confidence: 0.99988043

00:49:37.535 --> 00:49:38.035
disease

NOTE Confidence: 0.99730206

00:49:38.335 --> 00:49:40.015
and a primary breast tumor,

NOTE Confidence: 0.99730206

00:49:40.015 --> 00:49:41.375
who wants to tackle this?

NOTE Confidence: 0.99730206

00:49:41.375 --> 00:49:42.674
What is the current thinking

NOTE Confidence: 0.99982864

00:49:43.055 --> 00:49:43.954
on breast surgery?

NOTE Confidence: 0.9993698

00:49:45.135 --> 00:49:46.494
Doctor Ward wants to be

NOTE Confidence: 0.9993698

00:49:46.494 --> 00:49:47.395
a little provocative

NOTE Confidence: 0.85356647

00:49:47.820 --> 00:49:49.200
at our Smilo shares,

NOTE Confidence: 0.90869397

00:49:50.140 --> 00:49:51.760
Smilo share session.

NOTE Confidence: 0.97595435

00:49:52.060 --> 00:49:53.680
So the question is specifically

NOTE Confidence: 0.97595435

00:49:53.980 --> 00:49:56.219
asking if somebody has a

NOTE Confidence: 0.97595435

00:49:56.219 --> 00:49:58.540
primary breast cancer that's in

NOTE Confidence: 0.97595435

00:49:58.540 --> 00:49:59.920
the breast and they're diagnosed

NOTE Confidence: 0.97595435

00:50:00.140 --> 00:50:01.420
with that breast cancer, but

NOTE Confidence: 0.97595435

00:50:01.420 --> 00:50:02.320
they are found

NOTE Confidence: 0.99985135

00:50:02.635 --> 00:50:03.135
to

NOTE Confidence: 0.9993863

00:50:03.595 --> 00:50:05.515
have one or just a

NOTE Confidence: 0.9993863

00:50:05.515 --> 00:50:06.015
few

NOTE Confidence: 0.9996784

00:50:06.955 --> 00:50:07.455
spots

NOTE Confidence: 0.9866229

00:50:07.835 --> 00:50:09.435
on on a staging scan.

NOTE Confidence: 0.9866229

00:50:09.435 --> 00:50:10.555
So on a CAT scan

NOTE Confidence: 0.9866229

00:50:10.555 --> 00:50:11.755
or a PET scan, they're

NOTE Confidence: 0.9866229

00:50:11.755 --> 00:50:13.595
found to have another spot

NOTE Confidence: 0.9866229

00:50:13.595 --> 00:50:15.135
somewhere else in their body.

NOTE Confidence: 0.99923766

00:50:15.595 --> 00:50:16.815
Is there a role

NOTE Confidence: 0.9996683

00:50:17.859 --> 00:50:19.080
for doing surgery

NOTE Confidence: 0.9855938

00:50:19.540 --> 00:50:20.359
to the breast?

NOTE Confidence: 0.9918112

00:50:21.700 --> 00:50:23.380
Because at that point, kind

NOTE Confidence: 0.9918112

00:50:23.380 --> 00:50:24.660
of the traditional way that

NOTE Confidence: 0.9918112

00:50:24.660 --> 00:50:26.040
we think about this is

NOTE Confidence: 0.9918112

00:50:26.180 --> 00:50:27.940
that once the cancer has

NOTE Confidence: 0.9918112

00:50:27.940 --> 00:50:28.440
spread

NOTE Confidence: 0.99734426

00:50:28.820 --> 00:50:30.195
outside of the breast,

NOTE Confidence: 0.9923299

00:50:30.755 --> 00:50:32.695
it's no longer considered curable.

NOTE Confidence: 0.99889636

00:50:33.235 --> 00:50:34.055
And so

NOTE Confidence: 0.9564938

00:50:34.515 --> 00:50:35.575
curative approaches,

NOTE Confidence: 0.9896938

00:50:35.955 --> 00:50:37.495
including breast surgery,

NOTE Confidence: 0.9991009

00:50:38.515 --> 00:50:39.255
are generally

NOTE Confidence: 0.9976576

00:50:39.635 --> 00:50:41.094
not not considered.

NOTE Confidence: 0.9977241

00:50:42.114 --> 00:50:43.155
I'd say this is an

NOTE Confidence: 0.9977241

00:50:43.155 --> 00:50:44.755
area of a lot of

NOTE Confidence: 0.9977241

00:50:44.755 --> 00:50:45.255
research,

NOTE Confidence: 0.9997162

00:50:46.310 --> 00:50:46.810
especially

NOTE Confidence: 0.9972849

00:50:47.510 --> 00:50:48.010
in

NOTE Confidence: 0.9505772

00:50:48.310 --> 00:50:50.010
HER two positive breast cancer

NOTE Confidence: 0.9505772

00:50:50.150 --> 00:50:51.590
and in triple negative breast

NOTE Confidence: 0.9505772

00:50:51.590 --> 00:50:52.090
cancer

NOTE Confidence: 0.63875675

00:50:52.630 --> 00:50:53.130
because

NOTE Confidence: 0.83700883

00:50:54.070 --> 00:50:54.570
sometimes

NOTE Confidence: 0.97624385

00:50:54.950 --> 00:50:56.790
those types of cancers are

NOTE Confidence: 0.97624385

00:50:56.790 --> 00:50:58.170
very, very responsive

NOTE Confidence: 0.9997184

00:50:58.469 --> 00:50:59.130
to chemotherapy.

NOTE Confidence: 0.9580942

00:51:02.205 --> 00:51:03.725
The data that we have

NOTE Confidence: 0.9580942

00:51:03.725 --> 00:51:04.385
to date

NOTE Confidence: 0.99961096

00:51:04.765 --> 00:51:06.145
does not show a benefit

NOTE Confidence: 0.99961096

00:51:06.364 --> 00:51:06.864
to

NOTE Confidence: 0.9843315

00:51:07.645 --> 00:51:08.145
to,

NOTE Confidence: 0.9997678

00:51:08.765 --> 00:51:10.145
primary breast surgery

NOTE Confidence: 0.9909122

00:51:10.605 --> 00:51:11.505
in the setting

NOTE Confidence: 0.97627115

00:51:11.885 --> 00:51:14.045
of metastatic disease. But these

NOTE Confidence: 0.97627115

00:51:14.045 --> 00:51:15.565
studies aren't perfect, and so

NOTE Confidence: 0.97627115

00:51:15.565 --> 00:51:16.705
there are some ongoing

NOTE Confidence: 0.9856246

00:51:17.060 --> 00:51:18.739
studies being done to look

NOTE Confidence: 0.9856246

00:51:18.739 --> 00:51:20.900
at particular subsets of patients

NOTE Confidence: 0.9856246

00:51:20.900 --> 00:51:21.700
to see if there are

NOTE Confidence: 0.9856246

00:51:21.700 --> 00:51:23.000
benefits. And I,

NOTE Confidence: 0.99914896

00:51:23.460 --> 00:51:24.980
I will say that for

NOTE Confidence: 0.99914896

00:51:24.980 --> 00:51:26.359
all of the medical oncologists

NOTE Confidence: 0.9985847

00:51:26.660 --> 00:51:28.260
in our practice, we all

NOTE Confidence: 0.9985847

00:51:28.260 --> 00:51:29.080
have patients

NOTE Confidence: 0.98863286

00:51:29.859 --> 00:51:31.160
who have had,

NOTE Confidence: 0.9854103

00:51:31.645 --> 00:51:32.945
they may have had metastatic

NOTE Confidence: 0.9854103

00:51:33.085 --> 00:51:34.605
disease, and they may have

NOTE Confidence: 0.9854103

00:51:34.605 --> 00:51:36.125
had surgery, and they may

NOTE Confidence: 0.9854103

00:51:36.125 --> 00:51:37.185
have had radiation,

NOTE Confidence: 0.99551994

00:51:38.205 --> 00:51:39.885
very strong radiation with the

NOTE Confidence: 0.99551994

00:51:39.885 --> 00:51:41.905
goal of of trying to,

NOTE Confidence: 0.9979154

00:51:43.085 --> 00:51:43.585
sterilize

NOTE Confidence: 0.8473851

00:51:44.045 --> 00:51:44.545
metastatic

NOTE Confidence: 0.8008941

00:51:45.245 --> 00:51:45.745
deposits.

NOTE Confidence: 0.99947196

00:51:46.125 --> 00:51:47.025
And they do

NOTE Confidence: 0.9934254

00:51:47.540 --> 00:51:48.680
really, really well

NOTE Confidence: 0.9959084

00:51:49.060 --> 00:51:50.599
for a really long time

NOTE Confidence: 0.9959084

00:51:50.820 --> 00:51:52.260
and don't have evidence of

NOTE Confidence: 0.9959084

00:51:52.260 --> 00:51:54.260
further cancer. I know I

NOTE Confidence: 0.9959084

00:51:54.260 --> 00:51:56.359
know that there's at least

NOTE Confidence: 0.9959084

00:51:56.420 --> 00:51:57.700
one of them on this

NOTE Confidence: 0.9959084

00:51:57.700 --> 00:51:59.619
call right now who's who's

NOTE Confidence: 0.9959084

00:51:59.619 --> 00:52:00.599
listening in.

NOTE Confidence: 0.9668942

00:52:01.695 --> 00:52:03.215
People so we can't fully

NOTE Confidence: 0.9668942

00:52:03.215 --> 00:52:04.735
explain why that happens, but

NOTE Confidence: 0.9668942

00:52:04.735 --> 00:52:05.855
what what our goal in

NOTE Confidence: 0.9668942

00:52:05.855 --> 00:52:06.975
terms of the research going

NOTE Confidence: 0.9668942

00:52:06.975 --> 00:52:08.495
forward is is to figure

NOTE Confidence: 0.9668942

00:52:08.495 --> 00:52:08.995
out

NOTE Confidence: 0.99036777

00:52:09.535 --> 00:52:10.835
who are those patients

NOTE Confidence: 0.97721744

00:52:11.695 --> 00:52:13.215
that can benefit from a

NOTE Confidence: 0.97721744

00:52:13.215 --> 00:52:13.715
more,

NOTE Confidence: 0.98725104

00:52:14.820 --> 00:52:16.820
aggressive approach and continue to

NOTE Confidence: 0.98725104

00:52:16.820 --> 00:52:17.940
do well in the long

NOTE Confidence: 0.98725104

00:52:17.940 --> 00:52:19.860
run rather than go through

NOTE Confidence: 0.98725104

00:52:19.860 --> 00:52:21.000
very big surgeries,

NOTE Confidence: 0.9799126

00:52:22.020 --> 00:52:24.180
very aggressive treatments, and not

NOTE Confidence: 0.9799126

00:52:24.180 --> 00:52:25.560
benefit in the long run.

NOTE Confidence: 0.98138994

00:52:27.995 --> 00:52:29.114
Yeah. I think I think

NOTE Confidence: 0.98138994

00:52:29.114 --> 00:52:30.094
comes back to

NOTE Confidence: 0.9849335

00:52:30.635 --> 00:52:32.555
shared decision making and really

NOTE Confidence: 0.9849335

00:52:32.555 --> 00:52:34.555
looking at each individual patient.

NOTE Confidence: 0.9849335

00:52:34.555 --> 00:52:35.755
Bringing it back to tumor

NOTE Confidence: 0.9849335

00:52:35.755 --> 00:52:36.715
board, which is one of

NOTE Confidence: 0.9849335

00:52:36.715 --> 00:52:38.315
the questions that is densely

NOTE Confidence: 0.9849335

00:52:38.315 --> 00:52:38.815
packed,

NOTE Confidence: 0.9704558

00:52:39.835 --> 00:52:40.795
in one of our chat

NOTE Confidence: 0.9704558

00:52:40.795 --> 00:52:41.910
questions, which which is, does

NOTE Confidence: 0.9704558

00:52:41.910 --> 00:52:43.910
a single oncologist determine the

NOTE Confidence: 0.9704558

00:52:43.910 --> 00:52:44.950
treatment plan, or is it

NOTE Confidence: 0.9704558

00:52:44.950 --> 00:52:46.089
a collective decision?

NOTE Confidence: 0.9958923

00:52:46.469 --> 00:52:47.510
I can say that,

NOTE Confidence: 0.99863

00:52:48.390 --> 00:52:49.750
if it's if something is

NOTE Confidence: 0.99863

00:52:49.750 --> 00:52:50.569
very straightforward,

NOTE Confidence: 0.9875831

00:52:51.030 --> 00:52:52.230
the decision is made between

NOTE Confidence: 0.9875831

00:52:52.230 --> 00:52:53.670
the oncologist and the patient

NOTE Confidence: 0.9875831

00:52:53.670 --> 00:52:54.790
in the room right then

NOTE Confidence: 0.9875831

00:52:54.790 --> 00:52:56.844
and then. But any nuances,

NOTE Confidence: 0.9875831

00:52:57.065 --> 00:52:57.964
any complexities,

NOTE Confidence: 0.9942811

00:52:58.265 --> 00:52:59.625
I do wanna assure all

NOTE Confidence: 0.9942811

00:52:59.625 --> 00:53:01.065
of you that we're talking

NOTE Confidence: 0.9942811

00:53:01.065 --> 00:53:02.525
all among each other.

NOTE Confidence: 0.9748726

00:53:02.825 --> 00:53:04.105
We're bringing it back to

NOTE Confidence: 0.9748726

00:53:04.105 --> 00:53:05.085
tumor board,

NOTE Confidence: 0.97137135

00:53:05.785 --> 00:53:07.545
and also just encouraging you

NOTE Confidence: 0.97137135

00:53:07.545 --> 00:53:09.085
that if if you're unsure

NOTE Confidence: 0.97137135

00:53:09.224 --> 00:53:10.925
or want additional opinions,

NOTE Confidence: 0.9747879

00:53:11.360 --> 00:53:13.060
it's never wrong to explore

NOTE Confidence: 0.9747879

00:53:13.120 --> 00:53:14.800
second opinions. It's actually your

NOTE Confidence: 0.9747879

00:53:14.800 --> 00:53:16.020
right as a patient.

NOTE Confidence: 0.70512134

00:53:18.320 --> 00:53:18.820
Additional

NOTE Confidence: 0.99958694

00:53:19.200 --> 00:53:20.420
questions about

NOTE Confidence: 0.9145402

00:53:20.800 --> 00:53:21.300
just

NOTE Confidence: 0.9601195

00:53:22.800 --> 00:53:23.964
we kind of answered the

NOTE Confidence: 0.9601195

00:53:23.964 --> 00:53:25.005
question if it's a new

NOTE Confidence: 0.9601195

00:53:25.005 --> 00:53:26.765
cancer, are all markers tested

NOTE Confidence: 0.9601195

00:53:26.765 --> 00:53:28.045
again? And, yes, we we

NOTE Confidence: 0.9601195

00:53:28.045 --> 00:53:29.344
definitely wanna understand

NOTE Confidence: 0.9975582

00:53:29.885 --> 00:53:31.484
the biology of a new

NOTE Confidence: 0.9975582

00:53:31.484 --> 00:53:31.984
recurrence.

NOTE Confidence: 0.956725

00:53:34.605 --> 00:53:36.224
And I think maybe, Dan,

NOTE Confidence: 0.97586703

00:53:36.560 --> 00:53:37.680
take that first part of

NOTE Confidence: 0.97586703

00:53:37.680 --> 00:53:39.700
the question about late recurrences

NOTE Confidence: 0.97586703

00:53:39.840 --> 00:53:41.520
and hormone receptor positive breast

NOTE Confidence: 0.97586703

00:53:41.520 --> 00:53:42.020
cancer

NOTE Confidence: 0.9769302

00:53:42.320 --> 00:53:43.119
and how it can be

NOTE Confidence: 0.9769302

00:53:43.119 --> 00:53:44.800
different with different subtypes of

NOTE Confidence: 0.9769302

00:53:44.800 --> 00:53:45.300
cancer.

NOTE Confidence: 0.97299594

00:53:45.760 --> 00:53:46.960
Yeah. Yeah. That that is

NOTE Confidence: 0.97299594

00:53:46.960 --> 00:53:48.260
a that's a great question.

NOTE Confidence: 0.96241117

00:53:48.880 --> 00:53:50.555
So just like there are

NOTE Confidence: 0.96241117

00:53:50.555 --> 00:53:52.075
different subtypes of breast cancer,

NOTE Confidence: 0.96241117

00:53:52.075 --> 00:53:53.995
the the behavior of different

NOTE Confidence: 0.96241117

00:53:53.995 --> 00:53:55.435
cancers in terms of likelihood

NOTE Confidence: 0.96241117

00:53:55.435 --> 00:53:56.015
of recurrence,

NOTE Confidence: 0.97014815

00:53:56.315 --> 00:53:57.435
can be quite different,

NOTE Confidence: 0.9973912

00:53:57.755 --> 00:53:58.875
and the timing can be

NOTE Confidence: 0.9973912

00:53:58.875 --> 00:53:59.275
different.

NOTE Confidence: 0.9424371

00:54:00.315 --> 00:54:01.995
So, the the kind of

NOTE Confidence: 0.9424371

00:54:01.995 --> 00:54:03.195
rule of thumb is that

NOTE Confidence: 0.9424371

00:54:03.195 --> 00:54:04.175
the more aggressive,

NOTE Confidence: 0.94472194

00:54:04.475 --> 00:54:04.955
more,

NOTE Confidence: 0.79824543

00:54:05.275 --> 00:54:06.440
faster growing

NOTE Confidence: 0.96444607

00:54:06.980 --> 00:54:08.180
cancers, if they're going to

NOTE Confidence: 0.96444607

00:54:08.180 --> 00:54:09.800
recur, they're more likely

NOTE Confidence: 0.8062527

00:54:10.260 --> 00:54:11.000
to recur,

NOTE Confidence: 0.9803925

00:54:11.780 --> 00:54:12.920
in a shorter timeframe

NOTE Confidence: 0.88048553

00:54:13.540 --> 00:54:14.500
or at very least the

NOTE Confidence: 0.88048553

00:54:14.500 --> 00:54:16.280
highest risk periods for recurrence

NOTE Confidence: 0.9909881

00:54:16.660 --> 00:54:17.719
are earlier on.

NOTE Confidence: 0.9635917

00:54:18.627 --> 00:54:19.875
So for HER2 positive breast

NOTE Confidence: 0.9635917

00:54:19.875 --> 00:54:21.655
cancer, triple negative breast cancer,

NOTE Confidence: 0.9663307

00:54:22.915 --> 00:54:23.635
you sort of have the

NOTE Confidence: 0.9663307

00:54:23.635 --> 00:54:25.475
highest risk of recurrence over

NOTE Confidence: 0.9663307

00:54:25.475 --> 00:54:26.594
the first three and then

NOTE Confidence: 0.9663307

00:54:26.594 --> 00:54:27.955
over the first five years.

NOTE Confidence: 0.9663307

00:54:27.955 --> 00:54:29.315
And as you get further

NOTE Confidence: 0.9663307

00:54:29.315 --> 00:54:30.835
from that period of time,

NOTE Confidence: 0.9663307

00:54:30.835 --> 00:54:31.895
the likelihood of recurrence

NOTE Confidence: 0.9977442

00:54:32.275 --> 00:54:33.575
gets lower and lower.

NOTE Confidence: 0.8898175

00:54:34.280 --> 00:54:36.060
HER2 positive breast cancer,

NOTE Confidence: 0.86014396

00:54:37.400 --> 00:54:37.900
has,

NOTE Confidence: 0.99841475

00:54:38.719 --> 00:54:39.820
a lower

NOTE Confidence: 0.8941331

00:54:40.599 --> 00:54:42.119
or hormone receptor positive breast

NOTE Confidence: 0.8941331

00:54:42.119 --> 00:54:43.239
cancer has a,

NOTE Confidence: 0.9895508

00:54:43.800 --> 00:54:44.859
a lower likelihood

NOTE Confidence: 0.9987934

00:54:45.239 --> 00:54:46.619
of coming back

NOTE Confidence: 0.95551115

00:54:47.055 --> 00:54:48.494
period in most cases when

NOTE Confidence: 0.95551115

00:54:48.494 --> 00:54:50.015
sort of size and other

NOTE Confidence: 0.95551115

00:54:50.015 --> 00:54:51.395
things are all considered.

NOTE Confidence: 0.8823938

00:54:51.855 --> 00:54:52.355
So,

NOTE Confidence: 0.9112087

00:54:53.295 --> 00:54:54.335
so, for early stage breast

NOTE Confidence: 0.9112087

00:54:54.335 --> 00:54:55.775
cancer, hormones that are positive

NOTE Confidence: 0.9112087

00:54:55.775 --> 00:54:57.375
breast cancers are less aggressive,

NOTE Confidence: 0.9112087

00:54:57.375 --> 00:54:58.575
less likely to come back,

NOTE Confidence: 0.9112087

00:54:58.575 --> 00:54:59.555
generally speaking.

NOTE Confidence: 0.904491

00:55:01.080 --> 00:55:02.920
But that, that because they're

NOTE Confidence: 0.904491

00:55:02.920 --> 00:55:04.700
slower growing, sometimes the risk

NOTE Confidence: 0.904491

00:55:04.760 --> 00:55:05.420
of recurrence,

NOTE Confidence: 0.94934034

00:55:06.120 --> 00:55:06.860
over time,

NOTE Confidence: 0.96800774

00:55:07.480 --> 00:55:09.560
doesn't always drop off to

NOTE Confidence: 0.96800774

00:55:09.560 --> 00:55:10.060
zero.

NOTE Confidence: 0.99497813

00:55:10.840 --> 00:55:11.820
You can have

NOTE Confidence: 0.9474466

00:55:12.120 --> 00:55:13.500
a low risk of recurrence

NOTE Confidence: 0.9474466

00:55:13.560 --> 00:55:15.045
that can continue out for,

NOTE Confidence: 0.9474466

00:55:15.444 --> 00:55:16.344
for years sometimes.

NOTE Confidence: 0.9340904

00:55:17.525 --> 00:55:19.045
I think at, you know,

NOTE Confidence: 0.9340904

00:55:19.045 --> 00:55:20.085
twenty plus years,

NOTE Confidence: 0.9679045

00:55:20.484 --> 00:55:21.605
the likelihood of the cancer

NOTE Confidence: 0.9679045

00:55:21.605 --> 00:55:23.605
coming back is probably quite,

NOTE Confidence: 0.9679045

00:55:23.605 --> 00:55:24.344
quite low.

NOTE Confidence: 0.9303406

00:55:25.204 --> 00:55:26.405
You know, just the proof

NOTE Confidence: 0.9303406

00:55:26.405 --> 00:55:27.444
is in the pudding over

NOTE Confidence: 0.9303406

00:55:27.444 --> 00:55:29.145
time that it hasn't recurred.

NOTE Confidence: 0.8326131

00:55:30.540 --> 00:55:31.040
But,

NOTE Confidence: 0.9292423

00:55:31.580 --> 00:55:33.340
but there are situations, I

NOTE Confidence: 0.9292423

00:55:33.340 --> 00:55:34.300
think, that we've all seen

NOTE Confidence: 0.9292423

00:55:34.300 --> 00:55:35.500
where sometimes there can be

NOTE Confidence: 0.9292423

00:55:35.500 --> 00:55:37.500
late recurrence. And it's important,

NOTE Confidence: 0.9292423

00:55:37.500 --> 00:55:38.400
I think, for,

NOTE Confidence: 0.9810464

00:55:39.820 --> 00:55:41.440
for women to just be

NOTE Confidence: 0.9284056

00:55:41.739 --> 00:55:43.815
mindful of their bodies and

NOTE Confidence: 0.9284056

00:55:43.815 --> 00:55:45.255
what's going on, with their

NOTE Confidence: 0.9284056

00:55:45.255 --> 00:55:47.094
bodies and, you know, not

NOTE Confidence: 0.9284056

00:55:47.094 --> 00:55:47.575
be,

NOTE Confidence: 0.99910474

00:55:49.494 --> 00:55:50.795
shy about letting

NOTE Confidence: 0.8953158

00:55:51.655 --> 00:55:53.175
their doctors, be it an

NOTE Confidence: 0.8953158

00:55:53.175 --> 00:55:54.695
oncologist still or a primary

NOTE Confidence: 0.8953158

00:55:54.695 --> 00:55:56.234
care doctor, whomever they're

NOTE Confidence: 0.81941223

00:55:56.695 --> 00:55:57.835
getting their care from,

NOTE Confidence: 0.9098561

00:55:58.230 --> 00:55:59.690
know if if something feels

NOTE Confidence: 0.9098561

00:55:59.910 --> 00:56:00.410
unusual.

NOTE Confidence: 0.9680858

00:56:03.190 --> 00:56:04.550
Is it if that cancer

NOTE Confidence: 0.9680858

00:56:04.550 --> 00:56:05.590
comes back, is it always

NOTE Confidence: 0.9680858

00:56:05.590 --> 00:56:06.090
metastatic?

NOTE Confidence: 0.8251241

00:56:06.630 --> 00:56:07.910
Not necessarily. There are two

NOTE Confidence: 0.8251241

00:56:07.910 --> 00:56:09.035
types of recurrence. There's local

NOTE Confidence: 0.8251241

00:56:09.035 --> 00:56:09.064
recurrence and distant recurrence. And

NOTE Confidence: 0.8251241

00:56:09.064 --> 00:56:09.093
distant recurrence sort of refers

NOTE Confidence: 0.8251241

00:56:09.093 --> 00:56:09.610
to that that metastatic,

NOTE Confidence: 0.8887422

00:56:12.295 --> 00:56:13.595
And distant recurrence sort of

NOTE Confidence: 0.8887422

00:56:13.735 --> 00:56:14.215
refers to that, that metastatic,

NOTE Confidence: 0.8887422

00:56:14.455 --> 00:56:15.735
disease. The disease that's in

NOTE Confidence: 0.8887422

00:56:15.735 --> 00:56:17.015
organs outside of the breast

NOTE Confidence: 0.8887422

00:56:17.015 --> 00:56:18.055
or outside of the nearby

NOTE Confidence: 0.8887422

00:56:18.055 --> 00:56:19.895
lymph nodes. Local recurrence can

NOTE Confidence: 0.8887422

00:56:19.895 --> 00:56:21.575
be, the cancer coming back

NOTE Confidence: 0.8887422

00:56:21.575 --> 00:56:22.695
right in the breast either,

NOTE Confidence: 0.8887422

00:56:22.695 --> 00:56:24.099
you know, usually in the

NOTE Confidence: 0.8887422

00:56:24.099 --> 00:56:25.060
vicinity of where it was

NOTE Confidence: 0.8887422

00:56:25.060 --> 00:56:25.560
originally

NOTE Confidence: 0.9403748

00:56:26.099 --> 00:56:27.380
or sometimes in the lymph

NOTE Confidence: 0.9403748

00:56:27.380 --> 00:56:28.200
nodes that,

NOTE Confidence: 0.963437

00:56:28.820 --> 00:56:30.500
that are surrounding the breast

NOTE Confidence: 0.963437

00:56:30.500 --> 00:56:31.859
that is often the first

NOTE Confidence: 0.963437

00:56:31.859 --> 00:56:33.540
kind of place, cancer begins

NOTE Confidence: 0.963437

00:56:33.540 --> 00:56:34.839
to to travel to.

NOTE Confidence: 0.99084204

00:56:37.065 --> 00:56:38.525
So either of those situations

NOTE Confidence: 0.99084204

00:56:38.585 --> 00:56:39.545
are are possible. I mean,

NOTE Confidence: 0.99084204

00:56:39.545 --> 00:56:40.825
that's also the reason why,

NOTE Confidence: 0.99084204

00:56:41.065 --> 00:56:41.864
you know, it's important to

NOTE Confidence: 0.99084204

00:56:41.864 --> 00:56:42.844
keep getting mammograms.

NOTE Confidence: 0.9947665

00:56:43.224 --> 00:56:44.185
The the other reason why

NOTE Confidence: 0.9947665

00:56:44.185 --> 00:56:45.224
it's important to keep getting

NOTE Confidence: 0.9947665

00:56:45.224 --> 00:56:46.525
mammograms is because

NOTE Confidence: 0.90557796

00:56:47.864 --> 00:56:48.925
as long as you're,

NOTE Confidence: 0.9862917

00:56:50.200 --> 00:56:51.160
as long as you're a

NOTE Confidence: 0.9862917

00:56:51.160 --> 00:56:52.840
woman alive with breast tissue,

NOTE Confidence: 0.9862917

00:56:52.840 --> 00:56:54.040
there is some risk of

NOTE Confidence: 0.9862917

00:56:54.040 --> 00:56:55.500
developing a new breast cancer.

NOTE Confidence: 0.9812617

00:56:56.200 --> 00:56:57.560
And, and and just because

NOTE Confidence: 0.9812617

00:56:57.560 --> 00:56:58.520
you've had a breast cancer

NOTE Confidence: 0.9812617

00:56:58.520 --> 00:56:59.480
in the past doesn't mean

NOTE Confidence: 0.9812617

00:56:59.480 --> 00:57:00.280
that you can never have

NOTE Confidence: 0.9812617

00:57:00.280 --> 00:57:01.800
a breast cancer again. So

NOTE Confidence: 0.9812617

00:57:01.800 --> 00:57:03.100
continuing to get mammograms,

NOTE Confidence: 0.99138236

00:57:03.480 --> 00:57:04.734
so that you pick up

NOTE Confidence: 0.99138236

00:57:04.734 --> 00:57:06.255
on any new breast cancers

NOTE Confidence: 0.99138236

00:57:06.255 --> 00:57:07.455
when they're still early is

NOTE Confidence: 0.99138236

00:57:07.455 --> 00:57:08.114
is important.

NOTE Confidence: 0.9933444

00:57:08.494 --> 00:57:10.015
New breast cancers can can

NOTE Confidence: 0.9933444

00:57:10.015 --> 00:57:11.075
certainly show up.

NOTE Confidence: 0.9958896

00:57:12.015 --> 00:57:12.974
I could I could I

NOTE Confidence: 0.9958896

00:57:12.974 --> 00:57:13.474
could

NOTE Confidence: 0.97441757

00:57:13.775 --> 00:57:14.815
talk a little bit about

NOTE Confidence: 0.97441757

00:57:14.895 --> 00:57:15.695
I think we have a

NOTE Confidence: 0.97441757

00:57:15.695 --> 00:57:16.734
couple of Yeah. And then

NOTE Confidence: 0.97441757

00:57:16.734 --> 00:57:17.855
just to clarify for the

NOTE Confidence: 0.97441757

00:57:17.855 --> 00:57:19.200
audience that, but in the

NOTE Confidence: 0.97441757

00:57:19.200 --> 00:57:21.359
setting of active metastatic disease,

NOTE Confidence: 0.97441757

00:57:21.359 --> 00:57:23.700
you're getting thorough scans frequently.

NOTE Confidence: 0.92340726

00:57:24.320 --> 00:57:25.400
So in that setting, we're

NOTE Confidence: 0.92340726

00:57:25.520 --> 00:57:26.980
when we do not recommend

NOTE Confidence: 0.9902735

00:57:27.280 --> 00:57:29.359
additional routine mammography, that has

NOTE Confidence: 0.9902735

00:57:29.359 --> 00:57:30.400
not been shown to be

NOTE Confidence: 0.9902735

00:57:30.400 --> 00:57:30.900
helpful.

NOTE Confidence: 0.95340466

00:57:32.635 --> 00:57:34.315
We're almost at time. Just

NOTE Confidence: 0.95340466

00:57:34.315 --> 00:57:35.915
one remaining thing is that

NOTE Confidence: 0.95340466

00:57:35.915 --> 00:57:37.995
in metastatic disease, unlike early

NOTE Confidence: 0.95340466

00:57:37.995 --> 00:57:39.595
stage breast cancer, the treatments

NOTE Confidence: 0.95340466

00:57:39.595 --> 00:57:40.095
continue

NOTE Confidence: 0.9887136

00:57:40.715 --> 00:57:41.995
as long as they're helping

NOTE Confidence: 0.9887136

00:57:41.995 --> 00:57:43.275
you and as long as

NOTE Confidence: 0.9887136

00:57:43.275 --> 00:57:45.215
they're controlling the disease process.

NOTE Confidence: 0.98633426

00:57:45.515 --> 00:57:47.115
But there are situations where

NOTE Confidence: 0.98633426

00:57:47.115 --> 00:57:48.030
there may be,

NOTE Confidence: 0.9827176

00:57:48.670 --> 00:57:51.070
you know, we we've had

NOTE Confidence: 0.9827176

00:57:51.070 --> 00:57:52.430
times where disease has been

NOTE Confidence: 0.9827176

00:57:52.430 --> 00:57:53.710
completely stable for some time.

NOTE Confidence: 0.9827176

00:57:53.710 --> 00:57:54.750
So, again, comes back to

NOTE Confidence: 0.9827176

00:57:54.750 --> 00:57:55.970
shared decision making

NOTE Confidence: 0.99350566

00:57:56.350 --> 00:57:57.170
about whether,

NOTE Confidence: 0.9493262

00:57:57.870 --> 00:57:59.070
a certain type of,

NOTE Confidence: 0.97402155

00:57:59.790 --> 00:58:01.755
de escalation or therapy break

NOTE Confidence: 0.97402155

00:58:01.835 --> 00:58:03.535
can be considered. But, generally,

NOTE Confidence: 0.97402155

00:58:03.595 --> 00:58:05.134
things are left open ended

NOTE Confidence: 0.97402155

00:58:05.275 --> 00:58:06.394
as long as they're helping

NOTE Confidence: 0.97402155

00:58:06.394 --> 00:58:08.634
you and, keeping the disease

NOTE Confidence: 0.97402155

00:58:08.634 --> 00:58:09.295
at bay.

NOTE Confidence: 0.98618907

00:58:10.234 --> 00:58:11.835
Lots of different chemo cycles

NOTE Confidence: 0.98618907

00:58:11.835 --> 00:58:13.275
and targeted schedules, so we

NOTE Confidence: 0.98618907

00:58:13.275 --> 00:58:15.214
won't get into that. Definitely

NOTE Confidence: 0.98618907

00:58:15.275 --> 00:58:17.035
ask your oncology team about

NOTE Confidence: 0.98618907

00:58:17.035 --> 00:58:18.710
that. But you've all been

NOTE Confidence: 0.98618907

00:58:18.710 --> 00:58:20.390
such an amazing audience with

NOTE Confidence: 0.98618907

00:58:20.390 --> 00:58:22.550
really great questions, and I

NOTE Confidence: 0.98618907

00:58:22.550 --> 00:58:25.369
wanna thank again our speakers

NOTE Confidence: 0.98618907

00:58:25.430 --> 00:58:26.329
today, doctors,

NOTE Confidence: 0.950984

00:58:26.710 --> 00:58:28.250
Shellhorn and doctors O'Neil.

NOTE Confidence: 0.9369547

00:58:28.869 --> 00:58:30.150
And thank you so much

NOTE Confidence: 0.9369547

00:58:30.150 --> 00:58:31.829
for joining us. Thank you,

NOTE Confidence: 0.9369547

00:58:31.829 --> 00:58:33.130
Mary Ellen, for joining.

NOTE Confidence: 0.99775195

00:58:33.507 --> 00:58:35.127
Thank you. Bye bye.

NOTE Confidence: 0.8324726

00:58:35.667 --> 00:58:36.842
Bye bye. Okay, man.