Understanding Breast Cancer: Treatment Advances

October 21, 2021

Information

Smilow Shares | October 20, 2021

Presentations by:

Jane Kanowitz, MD Assistant Clinical Professor of Medicine (Medical Oncology)

Elizabeth Berger, MD, MS Assistant Professor of Surgery (Surgical Oncology)

Christin Knowlton, MD, MA Associate Professor of Clinical Therapeutic Radiology

ID7059

To CiteDCA Citation Guide

00:00Hi, I'm doctor Melanie Lynch and I'm the
00:03director of breast surgery at Bridgeport
00:05in the Yale Health system and I am so
00:08excited to be here tonight to hear the
00:11insights and advice from my dynamic
00:13and smart colleagues in New Haven.
00:16We will have three speakers tonight who will
00:19discuss innovations in Breast Cancer Care.
00:23And our first speaker will
00:26be Doctor Elizabeth Berger.
00:28She has both a Masters degree
00:30and a medical degree,
00:32and she's an assistant professor
00:33of surgery and oncology.
00:35Her medical degree comes from Loyola
00:37University in Chicago and where she was
00:40also a clinical research scholarship scholar,
00:42and she completed her fellowship in
00:44Breast Surgical Oncology at Memorial
00:46Sloan Kettering Cancer Center,
00:48where she was selected as a
00:51breast cancer Alliance Fellow.
00:53Her Master science comes from
00:56Northwestern University.
00:58Her research focuses in health
01:00outcomes for breast cancer patients,
01:02including quality care,
01:03and she's going to discuss
01:05innovations in breast cancer surgery.
01:09Great thank you Doctor Lynch for
01:10that very kind introduction and
01:12I'm excited to be here tonight.
01:13Thanks for everyone who's joined.
01:16Let me share my screen.
01:18And So what I hope to do tonight
01:21is just provide some updates
01:23in breast cancer surgery.
01:24You know things in Breast Cancer Care
01:26changes so frequently it's really hard,
01:28I think to stay up to date,
01:30time and so this is a a picture.
01:34It's a kind of famous social media trend
01:36that has been happening recently is you
01:38know how it started and how how is.
01:40Going so, Doctor William Halstead used to
01:42perform the holstead mastectomy or the
01:44radical mastectomy back in the late 1800s,
01:47where you know the entire breast
01:49as long as the as well as the PEC
01:52major minor muscle would be more
01:54removed and now Bernie Fisher,
01:56who actually recently passed away,
01:57who was instrumental in allowing
02:00really significant advances in
02:01breast cancer surgery for women,
02:03said, you know in God we trust all
02:05others must have data and he was,
02:07like I said,
02:08instrumental and allowing us
02:10to really deescalate.
02:11Our surgical operations for women
02:14and allow them to just really remove
02:17the area of tissue of the breast and
02:20not compromise any kind of uncle
02:22logic outcomes for our patients.
02:24So we talked a lot about D escalation
02:27of Breast Cancer Care and really
02:29what we're trying to do is provide
02:31as good of uncle logic outcomes
02:33for patients with less toxicity,
02:35less morbidity.
02:37And unless you know disfigurement of.
02:42Body and so in the 1970s is when we
02:44started to think about do we really
02:46have to do mastectomies for women or
02:48could we just perform lumpectomy's an ad?
02:51For instance radiation Doctor Nolan
02:52will talk about that a little bit later
02:54tonight and allow for similar outcomes,
02:56and that these trials really demonstrated
03:00that equivalency of survival and even
03:03really recurrence with the two operations.
03:05Then we thought we started thinking
03:08in the late 1990s that maybe women
03:11over a certain age.
03:12You could deescalate even radiation
03:14therapy for certain kinds of cancers.
03:17We also have really significantly
03:20deescalated axillary surgery,
03:21so armpit surgery of the lymph nodes
03:24and this has allowed women to spare the
03:27morbidity of significant lymphoedema
03:29in the arm range of motion problems.
03:31Sensory changes of the arm.
03:34And even into the 2000s,
03:37in the present day,
03:38the tailor X trial Dr.
03:41Kanowitz will talk a little bit more about.
03:42But we're thinking about even
03:45deescalating chemotherapy.
03:46For some women who have breast
03:47cancer in a specific type,
03:49and the comet trial is looking
03:51at ductal carcinoma insight,
03:52you or we call it pre cancer
03:54or stage zero cancer,
03:55depending upon what you read
03:56and where you read it,
03:57and maybe not even operating on
04:00some patients who have DCIS.
04:02So if a patient who has breast
04:05cancer need surgery,
04:06what are some of the updates recently?
04:08You know that we are doing actively,
04:10you know at smiling and across the country.
04:13Some of the techniques and localization.
04:15So finding the mass in the
04:17breast and being able
04:18to just do that one back to me have changed.
04:20We know that we need to get healthy tissue,
04:22around the lumpectomy.
04:23So what are some of the ideas
04:25of the of what margins mean?
04:27****** sparing mastectomy?
04:28So when a patient does need a mastectomy,
04:30what, as far as what are we
04:32doing for ****** sparing's?
04:33And how are we managing the armpit?
04:35The lymph nodes differently
04:37from you know years ago?
04:39And then I'll get into a very briefly.
04:41You know, are we operating on women
04:42who had stage four disease and you
04:44know a lot of people have high risk
04:46lesions that we're finding now.
04:47With, you know,
04:48improved screening mammograms and such.
04:49And what do we do with those
04:51high risk lesions?
04:51So just briefly,
04:52not all breast cancers are the same.
04:54We know one in eight women in this
04:57country will develop breast cancer,
04:59but there's a wide wide range of their
05:01diagnosis and included in those diagnosis.
05:04Are these this principle
05:06of receptors and you know,
05:08in a in a normal cancer in a I'm
05:10sorry a cancerous breast cell we often
05:12think about what actually feeds the
05:13breast cancer to cause it to grow.
05:16The cell growth and so some breast
05:17cancers have the estrogen receptor.
05:19Some have the progesterone scepter.
05:21Somehow this her two protein receptor.
05:23But again you know each breast
05:25cancer is an incredibly different
05:27kind of breast cancer and it's
05:29really unique to that individual.
05:30And so the main stages of Breast
05:33Cancer Care or a lot we do.
05:35It's a very multi modality type of disease.
05:38We think about surgery sometimes.
05:40We oftentimes we think about chemotherapy.
05:42We think about radiation and sometimes
05:44we think about underpinned therapy.
05:45If it's a hormonally driven cancer,
05:48but as a surgeon,
05:49I think surgery is the most important.
05:51Just kidding, of course,
05:53but I'm going to talk a little bit about
05:55surgical advance advancement of surgery,
05:57so when we think about
05:59lumpectomy versus mastectomy's.
06:01Some of the lumpectomy,
06:02UM advances we have seen is,
06:04how do we really localize the
06:06lesion or find that lesion?
06:08Because that little clip that we leave in
06:10the breast is of only two millimeters,
06:12and it would be like finding
06:13a needle in a haystack if we,
06:15as surgeons try to go in and
06:16just find it without help.
06:17So we used to use these wires.
06:20Wires used to be put into the breast
06:22and they still are at times when
06:24they're needed or and or appropriate,
06:26and the wires will be put in
06:28the same day of surgery.
06:29Sometimes the logistics get
06:30a little bit challenging.
06:31They can cause oh,
06:32are delays at times if the wire
06:34localization takes awhile,
06:36they can get dislodged.
06:37They're fairly uncomfortable as
06:39far as you know.
06:40You're getting wheeled down the day of
06:42surgery to the radiology department,
06:44etc.
06:44And of course,
06:45if something were to happen with
06:47the case gets canceled,
06:48then that wire must come out.
06:49You have it the way I
06:50would have to be placed.
06:51Again, an addition another day.
06:55You can kind of see the, UM, challenges.
06:57Sometimes of a liar placement that have
07:00to happen on the same day of surgery.
07:03And now what we've done is really decoupled.
07:05This idea of localization and surgery.
07:08And So what we've allowed to do
07:10is we can put these little tags
07:12or seeds in next to the clip.
07:15Here's a great example of A tag being
07:18put in right next to that biopsy clip,
07:20and the device gives off a signal.
07:23This tag gives off a signal
07:24to us in the operating room.
07:26And it allows us to find the lesion.
07:29UM, were sometimes able to do smaller
07:31lumpectomy is because of that.
07:32We tend to minimize over delays
07:34because they can be put in days before,
07:36for instance,
07:37and so we can start right at 7:30
07:39in the morning for operating cases.
07:41And oftentimes in various studies,
07:43it's shown to improve patient
07:46satisfaction with with surgery.
07:48So I try to explain often to my
07:50patients about margins and I think
07:52it's a challenging concept sometimes.
07:53So you know when we think about
07:55the cancer cells in the breast,
07:56there is often healthy tissue
07:58around the breast around.
07:59I'm sorry,
08:00the cancer cells and what we
08:01always want to try to make sure to
08:03do is at the edges of this piece
08:06of tissue we take out.
08:07We want to make sure we
08:09have healthy breast tissue.
08:11It is incredibly challenging and
08:12you know a frustration of all
08:15surgeons when you know we have some.
08:17Cancer at the edges and oftentimes
08:19it's it's cancer that we can't see.
08:21We can't feel, and unfortunately you know,
08:24it ends up being at the edge where
08:26it requires a second operation to
08:27go back and clean out the margins.
08:29There's a lot being done as far
08:32as trying to evaluate margins
08:33intraoperatively so at the same
08:36time of the operation.
08:38And unfortunately you know to date
08:41nothing has been demonstrated to be.
08:44As good as we would like it to be,
08:46to identify margin status
08:48intraoperatively so you know.
08:50Although it's a frustrating
08:52conversation to have with patients
08:53about how it takes about four to
08:55five days to get these results back.
08:56That's unfortunately where we're
08:57at right now, but you know,
08:59to be determined in the future if
09:01we'll have updates as margin status.
09:03So mastectomy is,
09:04I think the general consensus sometimes
09:06is that they're incredibly deforming,
09:09and that you know I'm going to
09:10leave me with it.
09:11You know, a terrible cosmetic outcome,
09:12but what we know now is that.
09:14We can do a lot of things to you know,
09:17allow women to hopefully feel you
09:19know as as natural as possible,
09:21especially with his ****** sparing approach.
09:23And we do think a ****** sparing
09:25approach is that you know a healthy
09:27approach to doing a mastectomy.
09:29This is a study looking at,
09:32for instance,
09:33women with genetic variants
09:35and allowing them a
09:37very very good outcome as
09:38far as a risk reduction.
09:40Actually one of our the authors
09:41here is Doctor Green up.
09:42One of our very own here at.
09:44At yield and so it's a really nice
09:47technique now for women where they're
09:50able to were able to save their
09:52******* during a mastectomy procedure.
09:56A lot of women think about
09:58removing their other breasts,
09:59so the contralateral or the
10:00other side breast when they have
10:02a diagnosis of breast cancer.
10:04And it's a you know it's a conversation
10:06I often have with patients we all
10:08probably often have with patients.
10:10And you know,
10:11I think it's always important to
10:12remember that breast cancer does not
10:14spread from one breast to the other.
10:15Rest, we do know that when
10:18women develop breast cancer,
10:19they have a higher risk of developing
10:21a breast cancer in the other breast.
10:23But we also know that when we do a
10:25contralateral or other sided mastectomy
10:27does not improve their survival
10:29from their original breast cancer.
10:31There are of course reasons to pursue you
10:34know contralateral prophylactic or surgery,
10:36you know in the other breast without
10:38breast cancer in it for many reasons.
10:39But it's not always right
10:42for every single woman.
10:43So as far as doing armpit
10:45surgery or maxillary surgery,
10:47you know we often test these Sentinel
10:50nodes using two different kinds of dyes.
10:53One is blue.
10:54You can see here.
10:55I tell my patients all the time
10:57the the lymph node lights up,
10:59and it turns blue.
11:00Or we use this Geiger counter here
11:02and it really makes a noise in
11:04the operating room and it beeps
11:06really loudly and it tells us what
11:08are the Sentinel lymph nodes?
11:10It's just a fancy word for saying kind
11:12of the first lymph nodes that drain.
11:14And these are the two mechanisms of how
11:16we find those lymph nodes and we remove them.
11:19I often hate this word as biopsy
11:21because all women we see have really
11:23gone through breast biopsies before.
11:24And it's not that we stick a needle
11:26into the lymph node and tests it.
11:28We actually remove those lymph nodes to
11:30make sure that there's no cancer in them.
11:33Like I said,
11:34just from the start of the presentation
11:36that we've really tried hard to
11:38deescalate or do less access or
11:40surgery for all the morbidity of it.
11:42And this was a in,
11:43you know.
11:44Credibly powerful study done in the
11:46early 2000s that demonstrated that
11:48all women who have out some disease
11:50in the lymph nodes don't need an
11:52axillary lymph node dissection or a
11:54removal of all the lymph nodes in the armpit.
11:56And it's really allowed a lot of
11:59women to spare an axillary lymph node
12:02dissection for their breast cancers.
12:04This is another trial that I think
12:06Dr Kanos will get into further,
12:08but this is even now looking at even
12:09women who have positive lymph nodes
12:12with hormone receptor positive disease.
12:13So we estrogen and progesterone
12:16positive diseases,
12:17even women who have positive
12:19lymph nodes might not necessarily
12:21need chemotherapy all the time.
12:23So we're giving chemotherapy
12:24a lot more often now before
12:27surgery to for various reasons,
12:28for various kinds of cancers and
12:31what we're realizing is surgeons
12:32is that we can still offer that
12:35Sentinel lymph node biopsy procedure
12:37as I just showed for women.
12:39Even who have chemotherapy first,
12:42and we don't always have to take out
12:44all the lymph nodes after chemotherapy.
12:46So if we use those two different dyes,
12:48the blue dye and the radioactive dye and
12:51we remove at least three lymph nodes.
12:53What we know is that that's
12:55safe for our patients to do,
12:56and if those lymph nodes
12:57don't have cancer in them,
12:58then we don't have to go on to an
13:01axillary lymph node dissection right now,
13:03the standard of care is that if
13:05any lymph nodes after chemotherapy
13:07still have cancer in them,
13:09we would go on and remove
13:10all the lymph nodes.
13:11But a lot of my patients I talked to,
13:14if they're an appropriate
13:16candidate for this trial.
13:17If there's an ongoing trial asking this
13:20question as to whether some patients
13:22who have a little bit of cancer.
13:24Still left in the lymph nodes
13:27after surgery and me and actually
13:29lymph node dissection.
13:31Or could they just get what we call
13:34radiation after surgery or and you
13:36know as Doctor Knowlton on the call she
13:38will talk a lot more about radiation
13:40but why I love Breast Cancer Care
13:42is 'cause it's so multi modality
13:43and multidisciplinary and we always
13:45are talking to our colleagues in
13:48the various specialties to try to
13:50take the best care of our patients.
13:52So stage four disease.
13:53So what do I even mean by stage four?
13:55Disease stage four diseases,
13:57those women who have breast cancer
14:00in other organs of their body?
14:03For instance,
14:03the liver or the lungs or the bones.
14:07And there have been various
14:10different data to suggest.
14:12Either we should remove the tumor
14:14in the breast if a woman has
14:16cancer elsewhere in the body,
14:17or we shouldn't remove it and there's
14:20varying thoughts on that, but.
14:22The recent very well known very
14:26well known very well done,
14:27randomized controlled trial done by
14:29a woman Doctor Khan at Northwestern
14:31really demonstrated that it's going
14:32to be most important for women
14:34who have stage four disease to
14:36get on systemic therapy.
14:37So some kind of therapy to treat their
14:40whole body and that oftentimes it doesn't.
14:42In fact,
14:43it really doesn't improve their
14:45survival to remove the original tumor.
14:47There are, of course,
14:48reasons to do surgery on patients
14:50who have stage four disease.
14:51If the.
14:52Wound is if the breast has a bleeding wound,
14:55or if there's pain,
14:56or you know something palliative
14:58to help local control,
15:00but we do think that really
15:02helping women who have stage
15:04four disease to get on some kind
15:07of medicine systemically is the
15:09best for them up front right now.
15:12And then last but not least,
15:13you know there's a lot of questions
15:15out there about high risk lesions,
15:17and this is a very complicated slide.
15:19Then I always told I was always told
15:20don't say that out loud 'cause you should
15:22change the slide if it's too complicated,
15:24but you know there are a lot of women
15:27are getting diagnosed with various kinds
15:29of high risk lesions such as radial
15:31scars or lobular carcinoma insight,
15:33Chu ductal carcinoma insight two
15:35versus lobular carcinoma inside shoe,
15:37and what we know about a lot of
15:39these high risk lesions or are.
15:41A fair amount increase your risk
15:43of developing a breast cancer,
15:44but not all have to come out.
15:46Some need to come out,
15:47and that's a conversation you
15:49know we often have with patients,
15:51but not all need to come out and so it it.
15:54It is constantly changing, getting updated.
15:57And you know if you ever have questions
15:59were obviously always available to answer
16:01them and that's all we have for tonight.
16:03So let me stop sharing my screen.
16:05Thank you for the opportunity to
16:07talk about the updates of surgery.
16:09Doctor Berger, two quick
16:12questions from the audience.
16:13One was there ever a time when you
16:16would use a wire localization instead
16:17of A tag or a seed localization?
16:21Yes, that's a great question,
16:22and absolutely so I think a couple examples.
16:26For instance, if we think that
16:28after a biopsy a patient has a very
16:31large hematoma associated blood
16:33collection around their cancer,
16:35it can be hard to put in that tag and
16:37get it in a place where we want it.
16:39Because there's a lot of fluid there,
16:42so the wire, for instance is a lot tends
16:45to be a little bit more accurate for
16:48localising lesion if there's if there's
16:50a fluid collection around the tumor,
16:53and then you know a second big reason
16:55sometimes is if there's a large area
16:58in the breast that we're trying to
17:00bracket or get the extent of the lesion.
17:02Sometimes wires can be easier to understand.
17:05The extent of the lesion and not
17:07putting in two tags, just two wires.
17:10Dumb and dumb, you know there's a few,
17:14probably other examples that I'm not
17:15maybe thinking off the top of my head,
17:17but I would say those are,
17:18you know, two of the bigger ones.
17:19Yeah, sometimes when it's just too close
17:21to the skin or something like that.
17:23And then there's one other question.
17:25How is it possible to have a
17:26negative Sentinel lymph node but
17:28a positive axillary lymph node?
17:33Yeah, the terrible part about
17:34cancer is that it likes to
17:36spread and that sometimes you know
17:38even if lymph nodes are negative,
17:40cancer can be in the rest
17:42of the body, even sometimes.
17:43So, although we think that the process
17:45is the cancer from the breast goes
17:48to the Sentinel or the first lymph
17:50nodes that drain the breast first,
17:52cancer doesn't always behave by their rules,
17:54so it does sometimes happen that way.
17:58OK. Thank you, that was terrific.
18:02So Doctor Kanowitz will be next,
18:05and she's an assistant professor of
18:07Clinical Medicine, medical oncology,
18:08and she's the medical director of the
18:11Smilow Cancer Hospital in North Haven.
18:14She received her medical degree
18:15from Cornell and completed her
18:17fellowship in medical Oncology,
18:18also at Memorial Sloan Kettering.
18:20So this kind of a alumni reunion.
18:25Prior to joining Neil Decker,
18:26Canyon once was the medical director
18:29from apology services at Bristol
18:31Hospital Cancer Care Center.
18:34And so doctor Kanowitz is going to talk to
18:36us about innovations in medical oncology.
18:41OK, I'm going to share my screen.
18:51OK, I usually introduce myself
18:53as I was born in Brooklyn.
18:56I'm the product of the public
18:59school education in New York City,
19:02and then I went to Med school.
19:04So thank you for inviting me to talk tonight.
19:08It truly is a privilege to help
19:11care for patients in this Community
19:13and to work along with Doctor
19:15Berger and Doctor Knowlton.
19:20I'm a medical oncologist.
19:22I prescribe systemic therapies.
19:24These are medicines that traveled
19:27throughout the body and treat
19:29cancer cells wherever they are.
19:31Why? Because breast cancer is both a
19:34local disease confined to the breast,
19:36but it's also a systemic disease.
19:39How do we know this?
19:41The year is 1968.
19:44Breast cancer is curable
19:47with radical surgery,
19:49and we saw those slides from Doctor Berger.
19:52Yet not all women remained cured.
19:56Doctor Fisher,
19:57who is a breast surgeon himself
20:00postulated and then proved that breast
20:03cancer is also a systemic disease,
20:06and he thought that unless we
20:08address microscopic cells that have
20:10traveled through the bloodstream,
20:13long term cure will be compromised.
20:17No, this is not our oncology clinic.
20:20During the height of the pandemic,
20:22these are the battlefields of World War One.
20:26What's war good for drug development,
20:29nitrogen gas or chemical warfare
20:33was noted to be toxic both to the
20:36bone marrow and to blood cells.
20:38And after the war it was the first
20:42anti cancer agent used to treat
20:45both leukemia and lymphoma cancers.
20:48Of the bone marrow and the blood.
20:51Let's go back to Doctor Fisher's time.
20:56We now obviously have more effective
21:00and safer chemotherapy drugs,
21:02and we have his new theory.
21:05A groundbreaking trial was designed
21:08to test his hypothesis.
21:10All women received curative surgery.
21:13Half the group received chemotherapy.
21:16Half the group didn't.
21:18The original study performed in the
21:2170s was actually performed in Europe.
21:24American surgeons would not let their
21:27patients participate because they
21:29felt that they could cure breast
21:32cancer and chemotherapy wasn't needed.
21:34This is the 20 year.
21:36Follow up with Doctor Fisher study
21:39that proves breast cancer is a
21:41systemic disease as well as locally.
21:44Clearly,
21:45the women who got advantor
21:48postoperative chemotherapy did better,
21:50and the value of participating in
21:53clinical trials cannot be overstated.
21:58This is your brain on drugs and
22:01I mean your blood on drugs.
22:03Germany had a lot of problems in the 1930s.
22:06You guessed it, how were they
22:09going to mass produce beer?
22:12The process of industrial
22:14fermentation grew into the fields of
22:17biotechnology and genetic engineering.
22:20This process was used for fuel,
22:23explosives and medicines
22:25like penicillin and insulin.
22:28In the early 90s the same process was
22:31used to create a white cell growth
22:34factor and this then allowed for safe,
22:37constant, safe,
22:39high concentrations of chemotherapy.
22:42The panel on the left is a sample of blood.
22:46The panel on the right is the
22:48same sample after the patient was
22:50given white cell growth factor.
22:52The purple cells are infection
22:54fighting cells.
22:58So now we can safely give high doses and
23:01the thought is chi chemotherapy works,
23:04maybe more. Chemotherapy is better.
23:08The era of high dose chemotherapy
23:11took place in the early 90s.
23:14The goal was to eradicate every last
23:17clone of breast cancer and then
23:20help the immune system reconstitute
23:22itself with this new growth factor,
23:25women were treated on clinical trials
23:28and yet many sought legal channels to
23:32get this new promising approach. That is,
23:35they sued their insurance company to get.
23:39This new technology?
23:41By the early 2000s,
23:43the jury was in the clinical trial.
23:47Data was reviewed,
23:48but the verdict was disappointing.
23:51This toxic approach did not improve outcomes,
23:55and again, it points out how important
23:58it is to participate in clinical trials.
24:03That's how we learn how to move
24:06the field forward.
24:08So maybe there's a better,
24:10more sophisticated way the human
24:14Genome Project was completed in 2003.
24:18It took 13 years to complete scientists
24:23all over the world worked together.
24:26Let me just repeat that.
24:28They actually worked together,
24:30and the entire human genome was identified.
24:36Using the same technology,
24:39a scientist at Stanford analyzed
24:42breast cancer tissue and he was able
24:46to identify distinct DNA patterns,
24:49but more importantly,
24:51he was able to correlate these
24:54patterns with outcomes.
24:56A risk assessment tool was
24:59developed for prognosis,
25:01gives us a better idea of what the
25:04future looks like and prediction what.
25:06What do we predict?
25:09The best postoperative approach to be?
25:13Prognostic and predictive factors are
25:16universally used in the postoperative
25:19management of breast cancer,
25:21and the goal is to stratify
25:23women into two groups,
25:25those who will benefit from postoperative
25:29systemic therapies and those for whom
25:32the toxicities outweighed the benefits.
25:36Classically,
25:36we've used the size of the tumor,
25:40the grade,
25:41the lymph node involvement to
25:44help guide us as to what to do.
25:47Now we have Oncotype and five or
25:50six other molecular studies where
25:53we look at the DNA of the cancer to
25:57predict the behavior of the tumor.
25:59So the size of the tumor women
26:02always ask what's my stage?
26:04It's all about the behavior.
26:06The biology size does not matter.
26:09We've heard it before,
26:10and you can quote me on that.
26:13If the risk is low,
26:15we use estrogen blocking tablets only.
26:18No chemotherapy is warranted.
26:20Dr Berger had mentioned some
26:23of the studies using Oncotype,
26:26Taylor X and RX Ponder so that
26:30we use these to guide us.
26:33You know, back in the old days,
26:35a decade ago,
26:36if the tumor was over half an inch,
26:39we prescribed chemotherapy.
26:45The excitement started in 1979.
26:49The gene, her two, was identified
26:52a scientist at Genentech,
26:55a new fledgling pharmaceutical company,
26:59discovered the gene and the
27:01protein that the gene encodes for.
27:06Genentech was just bought for $5
27:10billion this past year so if you
27:12were looking to buy it you lost out.
27:17Doctor Dennis Slamon,
27:19a medical oncologist,
27:21ran into this scientist at
27:24Genentech at the Denver Airport.
27:27They were both returning to California
27:31and they started talking and ultimately
27:33they both started to work together
27:35on the her two gene and hypothesized
27:39that overexpression or overactivity
27:42plays a role in breast cancer growth and.
27:47It causes the cancer to grow
27:50rapidly and spread.
27:52Their goal was to work on a medication that
27:56would target or block this growth signal.
28:00They ran out of money.
28:02What happened?
28:03An executive at Genentech came to the
28:06rescue when his mom was diagnosed
28:09with her two positive breast cancer.
28:14Harry Connick Junior played the
28:16role of Doctor Dennis Slamon in
28:19the lifetime made for TV movie
28:22about the development of Herceptin.
28:30So the left side is a a normal
28:34normal cell and we can see that the.
28:38That the her two receptors on the surface.
28:41It sends a message to the brain of the
28:45cell the nucleus hears or her two positive
28:49or overexpressing breast cancer cell and.
28:53And the message is there a lot of messages
28:55for the cancer cell to grow and divide
28:58being sent to the nucleus, Herceptin.
29:01And obviously we we found the same
29:05slide Elizabeth Herceptin blocks that
29:08message being sent to the nucleus.
29:11It shuts it down.
29:13In the 1990s, clinical trials again,
29:16clinical trials in advanced disease taught
29:20us that Herceptin is highly effective.
29:23Against her two overexpressing breast cancer,
29:26both when given with chemotherapy and
29:30also when given alone and in fact
29:33it's so effective that it was looked
29:36at in the postoperative setting in
29:39the early 2000s there were clinical
29:42trials all over the world comparing.
29:46Postoperative chemotherapy,
29:48with and without Herceptin.
29:52This data was presented at a big
29:56conference in 2004 in in this country.
30:00And. I I was at that meeting,
30:04everything stopped.
30:05You couldn't get into the room
30:07where the study was presented and
30:10there were monitors all all over
30:12the the pavilion all over the halls
30:15and everyone was just in awe.
30:18Adding.
30:19Adding Herceptin trastuzumab to post
30:22operative chemotherapy reduced the
30:24odds of the cancer coming back by 50%.
30:30There are now five or six.
30:33Targeted anti her to drugs.
30:37And these drugs and drug combinations
30:40are used in a host of clinical settings.
30:44These agents have tamed a very
30:47aggressive breast cancer and really
30:49changed the future for women diagnosed
30:52with her two positive disease.
30:55We're going to move on to another
30:57class of systemic therapies,
30:59anti estrogen therapy, or endocrine therapy.
31:03So estrogen is made in the ovaries
31:06and the adrenal gland and it's guided
31:10by communication and feedback between
31:12multiple organs, including the brain.
31:16Again, to understand where we are now,
31:19we're going to go back in time.
31:21This story starts in late 1800s.
31:24A scientist remove the ovaries of
31:28lactating rabbit and lactation or
31:31breast milk production stopped
31:33while why stop there the next year,
31:36he removed the ovaries of a woman.
31:39It was a pre menopausal woman
31:41with advanced stage,
31:42four incurable breast cancer and we
31:45saw that the breast cancer regressed.
31:49Estrogen was discovered in the 1920s
31:52and we subsequently learned about the
31:56relationship of estrogen to breast tissue.
31:59But it was clear that depriving breast
32:03cancer from estrogen was therapeutic,
32:06so over the next several decades,
32:09women were subjected to some very
32:12barbaric procedures to decrease estrogen.
32:15They had their ovaries removed.
32:17Adrenal glands removed.
32:19And even the pituitary gland in the brain.
32:26It wasn't until 1967 that
32:30tamoxifen was synthesized.
32:33It looks like estrogen and thereby
32:37blocks true estrogen from stimulating
32:40growth of breast cancer cells.
32:43It was initially used to treat
32:46advanced stage disease and in 1988,
32:50just like the studies using
32:53post operative chemotherapy,
32:54we learned that it decreased.
32:57The odds of the cancer coming
32:59back outside of the breast,
33:01just like chemotherapy did.
33:03And again we learned this
33:05through clinical trials,
33:07participation in clinical trials
33:10and tamoxifen is so effective that.
33:15It was proven in late 90s that it
33:18can be used as a preventive agent
33:21for women who are at high risk for
33:25the development of breast cancer.
33:27There are now multiple generations
33:30of anti estrogen therapies and
33:33anti estrogen drugs are amongst
33:35the most widely prescribed anti
33:38cancer agents in the world.
33:43The same way organs communicate to
33:46produce hormones like estrogen.
33:49There's a lot of communication within cells,
33:53both healthy cells and cancer cells.
34:00Walking or interrupting some of
34:04these internal messages can overcome
34:07resistance or enhance drug effectiveness.
34:12So a pellissippi or pick ray blocks,
34:16blocks and altered communication
34:20gene and makes anti estrogen
34:23therapy more effective everolimus.
34:26Bypasses a resistance mechanism and makes
34:31anti estrogen therapy effective again.
34:39Just like in life, there is a
34:41time and season for everything,
34:43and the same is true for breast cancer cell.
34:47There are times when the cell
34:49is more susceptible to the
34:52effects of anti estrogen therapy.
34:55And there are drugs.
34:58That do exactly that.
35:00Set the stage for the cancer
35:03cell being more effective.
35:05We have a reenactment below and
35:07and this is how I understand it.
35:10So this is how I explain it to patients.
35:12So whoops.
35:15OK, so on the left panel
35:18if I'm the cancer cell,
35:20Paula is the anti estrogen drug.
35:23She's trying to hurt me but I can
35:26still defend myself on the right panel.
35:29We can add in one of these cell
35:33cycle inhibitors that puts the
35:36the estrogen sensitive estrogen
35:39sensitive cell in a particularly
35:42vulnerable state for anti estrogen.
35:45Therapy, so Amy,
35:47who's who's holding my arms up,
35:50makes me vulnerable to Paula anti
35:54estrogen therapy and what we're
35:57seeing are unprecedented responses
36:00when we add cell cycle inhibitors
36:04to anti estrogen therapy and
36:08unprecedent durations of response.
36:11Gamechanger these drugs are now being
36:14looked at in the postoperative setting.
36:20Contrary to popular belief,
36:23most breast cancer is not inherited,
36:26and in fact only about 10% of women
36:30develop breast cancer because they've
36:34inherited that vulnerability from a gene
36:37like a mutated or altered BRCA gene.
36:40BRCA is repair gene and when it's mutated?
36:47It allows for the development
36:49of breast cancer because it
36:51no longer repairs the mistake.
36:53Parked inhibitors reset this repair
36:56process and this is yet another class of
37:01systemic agents that we use for women
37:05who have BRCA positive breast cancer.
37:08We not only use it in the metastatic disease,
37:11we now use it in the postoperative disease
37:14in the postoperative currative setting.
37:20Antibody drug conjugates.
37:22Chemotherapy of the future. I ask.
37:26Uhm, antibodies like Herceptin
37:28not only bind and block the cell
37:32surface proteins and block messages.
37:36They can really act like FedEx or
37:38Amazon and actually deliver packages.
37:41So antibody drug conjugates are
37:45antibodies where we attach chemotherapy,
37:48and then we deliver that
37:50chemotherapy not throughout the body,
37:52but directly to the cancer cell.
37:54So TDM one is Herceptin with the
37:59chemotherapy drug attached to it.
38:02Sacituzumab is another antibody to a surface.
38:06Protein called trope 2 and it's attached
38:09to a very potent chemotherapy drug
38:12that we commonly use in colon cancer.
38:22So I I think what I what I really
38:26want to what I really want to
38:29say is that the treatment today.
38:33Is were clinical trials yesterday and
38:35that's how we that's how we learn.
38:39That's how we move the field forward.
38:41So every time we participate
38:44in clinical research.
38:46We pay forward the benefits that
38:48we have for people behind us.
38:54And until every woman who's been diagnosed,
38:57or man who's been diagnosed
38:59with breast cancer is cured,
39:01there's still a long way to go.
39:11Needed to unmute myself there, sorry.
39:13Add two quick questions.
39:16The first comes from.
39:20Doctor Knowlton and she's asking about
39:22app Elicitive and if it's available
39:24off trial and are you using it?
39:27It is available off trial,
39:30so it's used in in the metastatic
39:33setting and there has to be.
39:36There has to be a certain alteration
39:39in the the pick three pathway,
39:42so we commonly test not not only
39:45do we do the Oncotype testing in
39:48the post operative setting for
39:51women whose disease has spread,
39:54we also do molecular testing.
39:58Looking for targeted agents and it's one
40:00of the first things that we look for,
40:03so we use it along with anti estrogen agents.
40:07And yes it's an FDA approved drug.
40:10And the second question is about
40:12standard endocrine therapy in
40:14combination with pick Ray from the
40:16start as the first line therapy so.
40:22Pic Ray has
40:24a lot of side effects.
40:26It's not a well tolerated
40:29drug and it's exciting,
40:31but I think we're finding right now
40:35more exciting the cell cycle inhibitors.
40:40So that's palbociclib.
40:41We have all these liquid names right?
40:44Palbociclib ribociclib abemaciclib
40:49they look so exciting.
40:51That they're all being looked at
40:53in the postoperative setting up,
40:56and it's a little early,
40:58but I do think that pick
41:00Ray will will be looked at.
41:02I think part of the part of
41:06the concern is some of these
41:08alterations or mutations only
41:11develop after someone's been
41:13exposed to anti estrogen therapy.
41:15We don't necessarily see them de Novo,
41:19so it's something that the cell.
41:21Learns to do too to overcome
41:26the anti estrogen effects.
41:28Good good, good question,
41:31good questions yeah.
41:33And and Doctor Knowlton,
41:35our third speaker tonight,
41:37excited to hear what she has to say
41:39about radiation therapy in breast cancer.
41:41Dr Knowlton is an associate
41:43professor in clinical,
41:44therapeutic radiology and medical
41:46director of the Smilow Cancer
41:48Hospital Care Center in Hamden.
41:50She received her medical degree at
41:52SUNY at Stony Brook and a Master of
41:54Arts from NYU and then completed her
41:57residency at Hahnemann University,
41:59Drexel University and her special.
42:02Realization in radiation
42:03therapy is for breast cancer,
42:04lung cancer and bone metastases,
42:07and in 2019 she earned the
42:09Smilow Luminary Award for
42:10excellence in Patient Care.
42:12So we're excited to hear
42:14we have to say thank you,
42:16thanks Doctor Lynch and thanks everyone.
42:18And welcome. I see a lot of
42:20patient names in the chat,
42:21so thanks everyone for coming and if some
42:25of you have seen me talk before at these,
42:27I promise you there's some new slides.
42:29If you bear with me alright,
42:31I'm going to share my screen now.
42:34OK, and from the beginning. Here we go.
42:39OK so I so this is me and I have no
42:44conflicts of interest to report.
42:46So I know that I tried not to be too
42:49repetitive from our our other panelists,
42:53but here's the basics on treatment for
42:56breast cancer, which we know often.
42:58Surgery is the mainstay of care,
43:01as both Doctor Berger and Doctor
43:03Kanowitz discussed at some points.
43:04Now, chemotherapy is becoming before surgery,
43:08but I'm the radiation oncologist,
43:09so I put the most basic format
43:12down here where surgery can either
43:14be breast conserving surgery.
43:16Where the breast is maintained and only
43:19the tumor is removed or mastectomy,
43:22where the entire breast is removed and
43:25there's obviously nodal surgery as well.
43:28That's involved in Doctor Berger
43:29talked a lot about the Sentinel lymph
43:32node biopsy and axillary dissection.
43:34And plus or minus chemo.
43:35As mentioned,
43:36the chemo can become come before
43:38the surgery and then plus or
43:41minus radiation therapy.
43:42After breast conserving therapy, usually yes.
43:45We offer radiation therapy but not always.
43:49And after mastectomy sometimes A and
43:50so and we will get into the details on
43:53that and how that's been evolving as
43:55part of this theme that you've been
43:58hearing a little bit about D escalation
44:00of care with the goal of reducing
44:03toxicity while maintaining good outcomes.
44:06And then there's hormonal
44:08therapy or targeted therapy.
44:10This would be the definitive
44:13treatment pathway.
44:14So what is radiation therapy?
44:18So it's a field of medicine that
44:20uses ionizing radiation to treat
44:22a variety of medical conditions,
44:24most often cancer.
44:25What radiation really is is that the
44:27packet of energy that moves through the
44:30air with the wavelength and frequency
44:32wavelength is how high and low does it go,
44:35and frequency is how quickly does
44:37it go through that weight length,
44:39and that the wavelength and
44:41frequency is what gives radiation.
44:43It's properties,
44:43so for example this radiation from the sun.
44:47There's radiation from the microwave,
44:48a light in your home is delivering radiation.
44:51It could be a blue light,
44:53and all of those different
44:54ways that if we can see it,
44:56if we can't,
44:57it's all related to the wavelength
44:58and frequency.
44:59So ionizing radiation is radiation.
45:01With enough energy and having those
45:04properties from its wavelength and frequency
45:07to remove an electron from an atom,
45:09causing that atom to become charged.
45:11And that's the basis for how it damages.
45:14The cells and so the plan.
45:16When you're treating somebody with
45:18the radiation is to get enough
45:20dose in there to kill whatever
45:22cancer cells you're aiming to kill,
45:24but but not damage the normal cells and
45:27and those of you who've had radiation.
45:30Oh yes, the normal cells do get damaged
45:32because that's why you get skin irritation.
45:35But the point is to allow
45:36the normal cells to repair.
45:38They are better at repairing
45:41from the damage from ionizing
45:43radiation than the cancer cells are.
45:46Uhm? Sorry I can't.
45:49I'm trying to fear we go OK, alright,
45:50so radiation therapy and breast cancer or so.
45:53The purpose is to eradicate residual
45:56disease within the breast or
45:58chest wall or the regional nodes.
46:00So that is the reason why
46:02following lumpectomy or the breast
46:04conserving surgery that radiation
46:06is usually offered because.
46:08We know from multiple studies that
46:10there is risk of having cancer cells
46:12left behind even in the setting of
46:15the most amazing lumpectomy ever,
46:17with nice negative nodes.
46:19And we treat higher risk patients
46:21following mastectomy,
46:23where we think that they are at
46:25greater risk to have residual
46:27cancer cells left behind.
46:28And we see here in this third bullet point,
46:30those would be patients with greater
46:32than 5 centimeters of tumor within
46:34the breast and or involved nodes.
46:36And we always want to use evidence
46:38based medicine,
46:39so we want to base our treatments on studies,
46:41not just on our feelings or what
46:43we think the best thing to do in
46:45our treatment is designed to treat
46:47the breast or the chest wall,
46:49plus or minus the regional lymph
46:51nodes depending upon if that's
46:53needed and to avoid the healthy
46:55tissues as much as possible.
46:56Even though I said that healthy
46:59tissues have the ability to repair.
47:01The heart and the lungs.
47:02They don't need to be radiated.
47:04They don't have Keith left behind in them,
47:07so we want to avoid the heart and
47:10the lungs to keep the toxicity down.
47:12And as it says at the bottom,
47:13a small amount of radiation
47:15to the normal organs is safe,
47:17but we try to avoid this as much as possible.
47:21So if someone were to come to
47:22see me in the office,
47:24the first step would be besides meeting
47:26a whole bunch of people before me.
47:28The registered nurse to do an intake,
47:31our social worker to introduce
47:33themselves to you,
47:35our advanced practice nurse.
47:36Also to kind of lay the groundwork.
47:38Then I would you would meet me and we
47:41would do an exam and we would talk about.
47:43We review your history.
47:45Make sure that I'm understanding
47:47everything that's happened and we
47:49would review why the radiation is.
47:51And if you've had breast conserving surgery,
47:54we would talk about a little bit about
47:56why that is and and how that help.
47:58Radiation can improve outcomes.
48:00If you had a mastectomy,
48:02you had reasons to have the radiation,
48:04such as involved nodes or a
48:06large tumor within the chest.
48:08We would discuss that as well.
48:10And we would talk about the treatment
48:13course and potential risks and the benefits.
48:16And then you know,
48:17if you were to agree to the radiation,
48:20we would then schedule the CT simulation.
48:23So that's the first step of our radiation.
48:25Is the planning is to do a CAT scan of
48:28the patient in the treatment position
48:31so they can design the radiation.
48:34When I first went into residency,
48:37we were not using CAT scans.
48:38Well they were just kind of becoming the.
48:41The norm, but just about when I started,
48:44we were using flora,
48:45which is a type of X ray and it was
48:48so it was much more rudimentary.
48:49Even in my somewhat brief career,
48:52I've seen such major changes,
48:54but the CT scan is used to design
48:56the radiation treatment plan and
48:58we do it in the treatment position.
49:00'cause if you think about it,
49:01that's the position we do this scan and
49:04that's the position we designed the plan in,
49:06and that's the position we need to get you in
49:09each day for the treatment and the treatment.
49:11Position is designed to give us the best
49:13access to treat what needs to be treated.
49:15The breast, the chest wall,
49:17the nodes and to stay off
49:20of the healthy tissues.
49:22There's no typically for
49:24breast cancer treatments.
49:25There's no dye given
49:27during these CT simulation.
49:29So the patient is typically
49:30placed on a breast board,
49:32with or without a mold underneath her,
49:33so this is and you could see
49:35in the top right that's.
49:36It's a standard breast board,
49:38so every day that a patient were
49:40to come in for her treatments,
49:42we would make sure that the breast
49:44full at the same and that arm
49:46bar that you see at the top that
49:47was in the same position.
49:49And then these this Ridge here at the
49:51bottom is called the bus stop so that
49:53you don't slide and everything needs
49:55to be in the exact same position when
49:57you come in for your treatment as it
49:59was for the planning scan and then
50:02we paste wires typically around the breast.
50:05These are these are only.
50:06Rudimentary field borders,
50:08but they do have importance
50:10'cause they're based on.
50:12When we were feeling,
50:13but we can make lots of adjustments
50:15to fine tune them based on the
50:17images that we get in the CAT scan.
50:19And here this patient in the
50:22bottom right has a scar wire
50:25also over her lumpectomy scar.
50:28So we placed wires around the
50:30breast tissue and on any relevant
50:32scars as a man and you will get
50:35tattoos to help us set you up in
50:38the perfect position each day.
50:39Typically a tattoo on the right lateral
50:42chest wall though between the breasts
50:44at the lower end at the bottom.
50:46And it maybe you can see this little dot
50:48on my wrist is an old fashioned tattoo.
50:51A lot of my patients in the audience you're
50:53going to say what that's old fashioned.
50:55I have that.
50:55Yes it is now will that fashion.
50:58Because now in the last 18 months,
51:00we've piloted throughout our Hamden
51:03and Greenwich Park.
51:04But it's been taken on at the
51:06other sites where we used tattoos
51:08that are only able to be viewed
51:10by the UV light so the patients
51:12don't have to have these constant
51:14reminders now of these tattoos on their
51:17bodies of their previous radiation.
51:19But we still have the benefit of the tattoo,
51:22which is a mark that won't wash off.
51:24And if a patient ever needs additional
51:26radiation, it does help us if we
51:28ever need to match prior fields.
51:32So excuse me. So after we do that,
51:36planning scan when we have to
51:38design the plan. So what happens?
51:40Well I have to draw on every slice of the CAT
51:44scan which is done in 2 millimeter slices,
51:48sometimes three, but typically two.
51:50What constitutes the breast tissue?
51:53What constitutes the tumor
51:55cavity or the lumpectomy bed?
51:57The various lymph node regions?
52:01The heart. In the lungs,
52:02so that the planning software
52:04can recognize it.
52:05So that's the first step.
52:07Then when I've done that,
52:08then I work with a certified medical
52:11dosimetrist that someone a dosimetrist
52:12is someone who has a four year
52:15degree in radiation planning and
52:17certified means nationally certified,
52:18and that the certified medical assistant
52:21I worked together to come up with a plan
52:24using the planning software to give
52:26an even dose to whatever needs to be treated.
52:29The breast, the chest wall,
52:30the nodes or not.
52:31Meaning that we don't have hot
52:33spots with extra radiation,
52:35or you limit those,
52:36and we obviously don't want cold spots
52:38where there's two little that's given,
52:40and we also want to analyze the
52:42dose to the heart and the lungs,
52:43and make sure that they are below
52:46what's considered safe thresholds.
52:48And let's say below sea threshold.
52:51But we can do a a plan where we're
52:53even get further below the safe
52:55threshold for the heart and the
52:57lungs you always want to do that.
52:59There's this principle and radiation
53:00oncology called ALARA as low as.
53:02Reasonably achievable,
53:03which means that you always want
53:06to have your nontarget tissues
53:09to be have their dose that they
53:12receive as low as possible.
53:14I'm so when we do when I'm eating a
53:16patient in doing the physical exam,
53:18looking for a lot of things,
53:21and one of the things I'm thinking
53:22about when I have the patient
53:24lay back on the table and put her
53:26arms up and feeling the breast,
53:27my mind is spinning about.
53:29What's the best position to
53:31treat this patient in?
53:33Is this patient going to be best
53:35treated in the prone position,
53:36lying on his or her for their stomach,
53:38or supine lying on the back?
53:41We can use different beam angles to come in.
53:43We want to.
53:44Angle the beam so that we stay
53:47anterior and lateral to the heart.
53:50We can use field and field which
53:51is the most modern technique.
53:53In fact another article came out just
53:54the other day that I need to read.
53:56It's sitting in my in basket but
53:57showing in the old days you had one
53:59beam from the medial and one from
54:01the lateral to treat the breast
54:02and you had some very minor ways
54:04that you could change how the dose
54:07was distributed within that beam.
54:09Now while a patient is being treated,
54:11there are leaves that are constantly
54:13opening and closing to change the
54:15shape of the beam and that'll help
54:17us avoid hot spots and cold spots.
54:20And it's been associated with a better
54:22cosmetic outcome, so all of our sites
54:25are using the field and field technique.
54:29Well, one thing that we can do the
54:31dosimetrist and I is design a custom
54:33made heart block and the head of the
54:36machine to make sure and I'll show
54:38you some pictures of that to make sure
54:40that the heart is not in the direct
54:42beam and the use of deep inspiration
54:43breath hold which I have some slides
54:45coming up and I know many of you who
54:47are treated with this technique.
54:49So here's the supine position
54:51IE lying on your back.
54:53We see that breast board here raised up
54:55the arm bars a little out of the field.
54:58There's a bus stop.
54:59Underneath this person's bottom,
55:01so the under the sheet that you can't see.
55:03And then of course,
55:04there's the pillow under the knees.
55:06So for this patient you know each
55:07day that she gets treatment that
55:09breast board is at the same height,
55:11the same pillow,
55:12under the knees everything is.
55:13And then we line up her tattoos.
55:16You can see that black X on the corner
55:18there which would which is helping to
55:20draw attention to where her tattoo is for us.
55:22That's the tattoo is just
55:24a little dot though.
55:25But we line up the tattoos to
55:27a laser grid in the treatment.
55:29Room that's calibrated daily by
55:31the medical physicist to make sure
55:34that the patient is not rotated
55:36and the position is spot on.
55:38So here's an example of right breast
55:40radiation in the supine position, IE.
55:43Lying on the back and the beam edge.
55:45You can see coming in here,
55:47and there's very little dose spillage
55:49that's deep to the beam edge because
55:51it's set up in what we call a tangent.
55:53It's not like two flashlights
55:55coming into that patient.
55:56What we do is we angle the beam
55:58so that the edge of the beam is
56:00what goes into treatment,
56:01and that causes what we call a
56:03non divergent posterior border
56:05where very little dose will will.
56:09We'll go behind or deep to those beams so
56:12you can see in this right breast patient.
56:13It's super easy to keep the
56:15radiation off of the heart,
56:16but we would still always use that olyra
56:18if we could do something where we still
56:20got the breast tissue in the way we liked,
56:22but we could spare the heart more,
56:24we would always go with that plan and
56:26this patient does have a small liver
56:28block you can see on the right photo to
56:30keep her liver out of the radiation beam.
56:35Here's a heart block, which is,
56:37you know, one of our tried true ways.
56:39Once we got the CT scan up going.
56:42You know 1010 to 15 years ago too.
56:46Had the direct beam,
56:48you could see that those are those leaves
56:49in the head of the machine that we can
56:51shape to follow the edge of the heart.
56:53You just have to be careful that
56:55when you're you can't just go
56:57crazy in designing the heart block
56:58while we love sparing the heart,
57:00we also want to make sure that if we go
57:02are too generous with the heart block,
57:04we won't treat the breast tissue properly.
57:08And here's the prone position.
57:10This is a patient laying on her
57:12stomach in the prone position.
57:15Some patients are excellent
57:16candidates and some are not.
57:18Who would be a poor candidate while
57:20a patient that tells me that she's
57:22highly uncomfortable lying on her
57:23stomach but not be the best candidate.
57:25There is certain positions of the tumor
57:28and exceptionally medial tumor is not
57:30always the best for prone positioning.
57:32For example,
57:33and we are not using prone
57:35positioning at our institution.
57:37If the nodes need to be treated.
57:41So here's some pictures of some
57:43radiation beams in the prone positioning,
57:46so you could see for this patient when
57:48you look on the picture on the left that
57:50mean edges cutting right through and
57:52that edge of the heart is right in there.
57:55But we see in the prone bone we're
57:57able to make the beam angle so
58:00that the heart stayed behind it,
58:02and another benefit of the prom for
58:05some patients can be if they have a a
58:08more pendulous breast with a larger.
58:11Fold underneath,
58:12that's an area that can get more
58:14skin irritation from the radiation.
58:16But if we treat the patient in the prone
58:18position, it'll lift the breast up.
58:21Helps a lot.
58:22We can see here for this patient on
58:25our left where the heart is going
58:27into the to the to the field edge,
58:30and here on our right with this
58:32patient holding her breath the hardest
58:34pulled completely out of the mean,
58:36but sometimes you may have had treatment
58:38with me and we did the breath hold,
58:40but I in the end I ended up
58:41treating you with the free.
58:42Breathing thing,
58:43or perhaps with your with
58:45another radiation oncologist.
58:46And that's because sometimes
58:48it's really not needed.
58:49The heart is sometimes nicely
58:51out of the field even
58:52without the DIBH,
58:54and it does allow a shorter treatment
58:56time on the treatment table if you
58:58are treating with the free breathing.
59:01So, so that's kind of the basics
59:03about radiation and where we've come
59:05and sort of the most modern techniques
59:07to treat the breast and the nodes.
59:10Try to keeping the event,
59:11the doses even as possible and
59:13sparing the lung and heart as most
59:16as pop as most as we possibly can.
59:19Umso D escalation of treatment for breast
59:22cancer is interesting in radiation,
59:24because of course it's related to toxicity,
59:28but it's also related to how
59:29many treatments you have to come
59:31for and people might say, well,
59:32how is that D escalation of treatment?
59:34Well, you think about it,
59:36it's less time away from a patient's family,
59:38their personal life,
59:39less time off from work and people can
59:42have financial toxicity from their way
59:45from their cancer treatment.
59:47And so if we can help patients.
59:49Finish their treatments and get back
59:51to work or get back to doing the
59:54things that they enjoy more quickly
59:55without compromising outcomes.
59:57That sounds like the best plan
59:59so conventional whole breast
01:00:02irradiation was five to six weeks,
01:00:05so five weeks to the whole
01:00:07breast and then a boost,
01:00:08which is an additional treatment to
01:00:10where the tumor was in 5 to 8 fractions.
01:00:12So people were getting treated
01:00:14for five to six weeks,
01:00:16even if they had an early stage cancer.
01:00:18Just following them back.
01:00:20To me, however, now there's three
01:00:24well done randomized trials,
01:00:26all with 12 years of median fault.
01:00:28Meaning half of the patients
01:00:30have been followed for longer
01:00:31that support a shorter course of
01:00:33treatments for patients who receive
01:00:35radiation to the breast alone,
01:00:37and there's a 16 fraction regimen to the
01:00:41breast that would use a four fraction boost,
01:00:43or 15 fraction regimen.
01:00:44That's what we use.
01:00:46So most of our patients now,
01:00:48if the nodes don't need to be treated,
01:00:49are getting.
01:00:50Treated in 15 or 19 treatments,
01:00:53so three or four weeks as
01:00:55opposed to the five to six weeks.
01:00:57Uhm,
01:00:58others other trials have found that
01:01:02there's decreased the large tiles,
01:01:05found no statistical difference
01:01:07between outcomes and no statistical
01:01:10difference between the side effects,
01:01:13so they were unchanged,
01:01:15although there were some quality of
01:01:17life surveys that went along with it
01:01:19that did find improved quality of life
01:01:21for patients with the shorter course.
01:01:23But some non randomized and smaller
01:01:25trials have found decreased toxicity.
01:01:28Obviously,
01:01:28the decreased healthcare costs
01:01:30and improved patient convenience
01:01:32with the shorter course.
01:01:34Uh,
01:01:34so I talked about how at Yale
01:01:36were doing the the 15 fractions
01:01:38to the whole breast plus or
01:01:41minus the four boost patients,
01:01:43and this is typically without
01:01:45additional nodal fields.
01:01:46And when when the breast is intact,
01:01:49that being said,
01:01:50there are some ongoing studies to say hey,
01:01:53is this safe to do?
01:01:54If a patient had mastectomy?
01:01:57If you need to treat the patients
01:01:59nodes and they're all looking very
01:02:02promising and in very select cases.
01:02:04Following mastectomy,
01:02:05I've started using the Hypo frac.
01:02:09The shorter course of treatment,
01:02:11the three to four weeks rather than the
01:02:13five to six in the setting of trading.
01:02:16The nodes or following mastectomy.
01:02:20I talked about a boost so I just
01:02:22wanted to put this on briefly
01:02:23to show you a boost is typically
01:02:25four or five extra fractions
01:02:27to where the tumor was a man.
01:02:29They are after the whole breast treatment.
01:02:32They're sort of like the bonus they
01:02:34the boost has been shown in the
01:02:37setting of lumpectomy to be helpful
01:02:39for patients of all ages from under
01:02:4245 to go up to the into the 80s.
01:02:45Really, however, the UM,
01:02:48their update on the boost trials.
01:02:50They were mostly done in the 90s.
01:02:52There is the boost and no boost
01:02:54trial and they'll be on trial.
01:02:55They've been so those patients
01:02:57have a lot of median
01:02:58follow up now and they did publish a 20
01:03:01year update and they've said that found
01:03:04that it was most beneficial for while.
01:03:06It did still benefit patients of all ages,
01:03:08it was most significant to
01:03:10benefit women age 60 and under.
01:03:12I do tend to offer the boost for
01:03:14pay if we're doing the modern
01:03:16hypofractionation to offer the boost
01:03:19for both patients under 70, we know.
01:03:2170s The new 60 but I do talk about
01:03:25it with people that I've as an
01:03:28option and what are their goals?
01:03:31So now we're getting even shorter,
01:03:33Ultra Hypo fractionation.
01:03:35We have the fast regimen which looked
01:03:39at these five fraction courses.
01:03:41They actually compare them back
01:03:43to the older five week course.
01:03:46The 25 fraction courses,
01:03:48which just makes sense that 25 fraction
01:03:50court has decades of data behind it,
01:03:52so they were really comparing it to those.
01:03:55Gold standard and these were once a week,
01:03:58so once a week for five weeks and
01:04:00at 10 years and we liked this
01:04:02ten years in a randomized trial.
01:04:04Which is the best type of trial to look for?
01:04:07Good evidence?
01:04:07There was no significant difference
01:04:09in normal tissue effects and outcomes.
01:04:12Local regional recurrence,
01:04:13distant recurrence,
01:04:14overall survival were the same,
01:04:17so the NCCN,
01:04:18which is a National Cancer
01:04:21Consortium network,
01:04:22has has updated their recommendations.
01:04:25To say that we can use the fast regimen or
01:04:28consider it at least for people over 50,
01:04:31although I tend to be a little over
01:04:3360 with early stage breast cancer,
01:04:36meaning they have a DCIS or a
01:04:38smaller tumor and negative nodes
01:04:40who do not require a boost.
01:04:42That is why I am I try to have my
01:04:45patience that we consider this for be
01:04:49over 60 because remember the boost was
01:04:51really beneficial for everybody that
01:04:53was under 60 and there's no boost.
01:04:55Component to this fast regimen we have
01:04:58not started using a Fast forward at Yale.
01:05:01They are using it at some institution.
01:05:03I know MD Anderson is using it,
01:05:05for example,
01:05:05where those five treatments rather than once
01:05:08a week are just given Monday through Friday.
01:05:11But we're not quite yet ready for that here.
01:05:15We like to see a little MD Anderson said.
01:05:17Awesome place, believe me,
01:05:19but we would feel more comfortable
01:05:21with a little bit longer data.
01:05:23As you can see on my slide here,
01:05:25there's just five years of data.
01:05:27Rather than attend that we
01:05:28have for the fast regimen and.
01:05:31And so we'd like to wait a
01:05:33little bit longer on that.
01:05:35And the fast is used for selected
01:05:37patients at Yale, the once a week.
01:05:40Not the Fast forward yet.
01:05:42Uhm, but what about omitting the radiation?
01:05:45Maybe some people don't even need
01:05:47the radiation, and that's true.
01:05:49This CL GB 9343 is often quoted,
01:05:52and if patients make this criteria,
01:05:55there are 70 or greater their tumors,
01:05:572 centimeters or less,
01:05:59they have an estrogen receptor
01:06:00positive cancer.
01:06:01Their node native on their
01:06:04surgical procedure,
01:06:05or if they did not have any nodal surgery
01:06:07on the exam and imaging and the patient.
01:06:10This is starred because the patient needs.
01:06:12Be willing and able to
01:06:14take endocrine therapy.
01:06:15The pill that doctor Kanowitz
01:06:17discussed for five years.
01:06:19We really not quite there yet,
01:06:21especially with no Angevin treatment.
01:06:25After a lumpectomy for surgery,
01:06:27we do like to see some sort of
01:06:30additional insurance policy,
01:06:31whether it's.
01:06:32Radiation, or the pill and the other
01:06:36reason is too is that all patients on
01:06:37this trial did take the pill for five years.
01:06:40So at 10 years the local regional
01:06:42recurrence was super low with the
01:06:45tamoxifen only the endocrine pill,
01:06:46only it was 10%.
01:06:49A local regional recurrence,
01:06:51so 90% of patients basically not
01:06:54experiencing a local regional
01:06:56recurrence are 98% of patients in
01:06:59the radiation plus tamoxifen arm.
01:07:01She might say, well, hey, it doesn't that.
01:07:04Eight 8%. Make me have beating and it does.
01:07:08It was statistically significant.
01:07:09It does mean if you skip the radiation
01:07:11of 8% greater chance of having the
01:07:13cancer returned in the breast.
01:07:14But frankly,
01:07:15a 90% chance of going 10 years without
01:07:17getting the breast cancer back in
01:07:19the breast is pretty good odds.
01:07:21But here's the real reason why
01:07:23it's OK to omit the radiation.
01:07:25It's because there was no difference
01:07:26in the breast cancer specific survival,
01:07:28which was excellent on both arms.
01:07:31No difference in overall survival,
01:07:33which was the same in many patients
01:07:35in this age group.
01:07:36Ended up dying of something else.
01:07:38No difference in time to metastasis or
01:07:40the development of distant metastasis.
01:07:43So the 10 year probability of freedom
01:07:45from metastasis was 95% in both arms,
01:07:48so the radiation didn't do anything
01:07:50to improve overall survival.
01:07:51For this.
01:07:52For these patients that meet this
01:07:54criteria to prove overall survival
01:07:56breast cancer specific survival or the
01:07:59risk for cancer developing elsewhere.
01:08:01We may see in the next few years
01:08:04that we're opening up this idea
01:08:06of not having the radiation after
01:08:08lumpectomy to more patients.
01:08:10The prime two trial enrolled
01:08:13women 65 and older.
01:08:14Although the number of patients aged
01:08:1765 and 66 was quite low on the trial.
01:08:20But 60, but still the upper 60s.
01:08:22Now it's opening for them,
01:08:23and it did allow some larger tumors.
01:08:27Up to three centimeters.
01:08:29They did have their 10 year update
01:08:33recently at I believe it was at Astro
01:08:35last year or San Antonio Breast conference.
01:08:37I forget,
01:08:38but the they have not published the
01:08:41peer reviewed paper yet and we like to
01:08:44wait for the paper rather than just the.
01:08:47Presentation at the conference.
01:08:50Doctor Berger talked about omitting
01:08:53radiation in ductal carcinoma insight.
01:08:55Two, so we are at Yale.
01:08:58We have the comic trial that's open.
01:09:00Our principal investigators,
01:09:03Dr Golshan,
01:09:04but it is looking now at withholding
01:09:06even surgery in grade one and grade two.
01:09:09Ductal carcinoma insight do.
01:09:11And therefore,
01:09:11if these patients don't have surgery,
01:09:13they're not going to be having radiation.
01:09:15Lord is the same trial open
01:09:17over in Europe and there's
01:09:19actually 4 international trials.
01:09:21Comet Lord and two others
01:09:23whose names are escaping me,
01:09:24but I do know that the principal
01:09:26investigators on all of them meet regularly,
01:09:28and they're going to share their data,
01:09:30which is going to give us a
01:09:32lot of great information.
01:09:34And so we're really looking at
01:09:36can screen detected low risk
01:09:38DCIS that's found on mammogram?
01:09:40No symptoms with presentation like no
01:09:42bloody ****** discharge or anything and
01:09:44if it has to be grade one or grade two,
01:09:46can it be managed successfully with just
01:09:50active surveillance and no surgery?
01:09:52Uhm, that's the end of my talk and
01:09:55I'm happy to answer any questions.
01:09:57And I'm sorry that we went over from the
01:10:008:00 o'clock bravo that was wonderful.
01:10:03Thanks.
01:10:04There are a bunch of questions for you.
01:10:07The first question is about
01:10:09having a lumpectomy back in
01:10:122009 with mammosite radiation.
01:10:15And Mammosite isn't currently used as much,
01:10:18and the long, long term safety
01:10:21of mammosite still good is.
01:10:23The date is still good.
01:10:24And why isn't mammosite used anymore?
01:10:26OK, that's a great question.
01:10:29Well, so one of the reasons that we were the
01:10:32mammoth site is perfectly fine treatment,
01:10:34especially for well chosen patients in.
01:10:37The suitable category for for
01:10:39what we call partial breast,
01:10:41where we treat just where the tumor was.
01:10:43And that's patience with the lower
01:10:45grade small or earlier stage cancer.
01:10:48You know, no nodal involvement
01:10:50and actually the outcomes,
01:10:51as far as recurrence and control
01:10:54of the cancer they have done well.
01:10:58So why do we stop them?
01:10:59Amosite?
01:11:00Well, it is a bit of an invasive procedure.
01:11:02For those of you who don't know it,
01:11:03it has a device.
01:11:05A balloon device that sits within the.
01:11:09Tumor bed and you have a lumen that
01:11:11escapes from the body and it's so it's
01:11:14so nor attached in and the patient
01:11:17has that device in her breast for
01:11:19a week while she gets twice daily
01:11:22radiation therapy for Monday through
01:11:23Friday or for five days so well as
01:11:26convenient that it was done with a week.
01:11:29But it does have that invasive
01:11:30component of having a foreign
01:11:32body in the in the breast,
01:11:34which can be uncomfortable for some people,
01:11:36but the what was really the problem.
01:11:39Was that the cosmetic outcome
01:11:41was not so hot patients.
01:11:44Some trials have not shown this,
01:11:46but others have shown that there
01:11:49is more fibrosis in the breast,
01:11:51meaning firm tissue after the treatment.
01:11:53Sometimes that can be uncomfortable
01:11:56for patients.
01:11:57The appearance of the breast
01:11:59was not as good and now that we
01:12:02have are embracing these shorter
01:12:04courses of treatment for patients.
01:12:07That don't would they don't require having
01:12:10a something invasive in the breast.
01:12:12We stopped offering the mammoth site
01:12:14at at Yale because of that because we
01:12:16were able to offer patients shorter
01:12:18course treatments without requiring that.
01:12:20But as far as cancer recurrence,
01:12:23the data is still excellent for
01:12:25well chosen patients,
01:12:26and I think I did see that you
01:12:27had a doctor carcinoma.
01:12:28Insight two in the in the questions,
01:12:31and so I would not. That should not.
01:12:33That is not why we stopped it.
01:12:34We did not stop it because
01:12:36of concerns about recurrence.
01:12:38OK, and then there's another
01:12:40question about side effects.
01:12:41First, what are the side effects
01:12:45associated with the fast treatment
01:12:47and is how does it compare to regular
01:12:51radiation and then Part B is with?
01:12:54How can you avoid the fight?
01:12:55This side effect of a radiation burn?
01:12:58You know these significant
01:12:59changes to the soft tissue,
01:13:02so it is true that the shorter course is
01:13:05the three to four weeks while it wasn't.
01:13:09On those larger trials, showing a
01:13:11significant decrease in skin toxicity,
01:13:13smaller trials have shown have shown
01:13:15that there is less toxicity with
01:13:16the shorter course going from three
01:13:18to four weeks from the five to six,
01:13:20and subsequently as well the fast
01:13:22to the once a week for five weeks.
01:13:26The data showed no significant difference.
01:13:28However, I will the patients that
01:13:31we observe they do tend to have
01:13:34less side effects than.
01:13:36Than acute side effects,
01:13:37IE skin reaction then people that
01:13:39are undergoing the longer course of
01:13:41treatment just from what I see them
01:13:43during their weekly skin checks and
01:13:45see them for their follow up with me.
01:13:47You know, two months afterwards.
01:13:48I know we're not supposed to
01:13:50use what observation ULL data,
01:13:51but we've seen it,
01:13:52but so I would say that that we are
01:13:55seeing less less skin toxicity with
01:13:57the shorter courses and so with
01:14:00the fast having the least amount
01:14:02of skin toxicity to prevent it.
01:14:05Well, we prescribe.
01:14:06A steroid cream called mometasone.
01:14:09There's nothing to prevent it.
01:14:10Everybody gets some skin irritation
01:14:13to some degree.
01:14:15What we can do in the planning and limit
01:14:17those hotspots as much as possible,
01:14:19which we talked about a little bit,
01:14:20but then we do prescribe a
01:14:23steroid cream called mometasone.
01:14:24There was a well done randomized trial
01:14:26looking at patients using mometasone.
01:14:28This steroid cream once a day Monday
01:14:30through Friday and the weekends for one
01:14:33and up to one to two weeks afterwards.
01:14:35It actually had no negative side
01:14:37effects on the trial that showed
01:14:39reduction in acute skin toxicity.
01:14:41It doesn't mean it made it zero,
01:14:43it was just reduction.
01:14:44But you know, everyone's.
01:14:46Different, their skin is different.
01:14:48But we we also provide a
01:14:50high quality moisture lotion.
01:14:52You don't have to use ours,
01:14:53we just like stuff that doesn't have
01:14:55a lot of scent or is it heavy on
01:14:59the antioxidants during treatment?
01:15:01Uhm and then drinking water and
01:15:04eating protein and allowing yourself
01:15:06to rest and giving it time.
01:15:13Great thank you.
01:15:14Any other comments from
01:15:16anybody on the panel? Uhm?
01:15:21Doctor Berger's answer
01:15:22on active surveillance,
01:15:24which is also a hot topic too.
01:15:27I don't think it went to Barbara, so I'll
01:15:29send it to the person who asked, sorry.
01:15:34Alright, well thank you so much and
01:15:36thank you for everyone who joined
01:15:39us tonight for this really great
01:15:41forum and we're just so excited to
01:15:44have such talented and dedicated
01:15:45physicians in all of our care centers.
01:15:48So thank you again for all of your
01:15:51leadership and have a good night. Thank you.
01:15:54Thanks everyone.