Dr. Lyndsay Harris and Dr. Gina Chung, New Treatment
Advances for Breast Cancer
March 23, 2008
Welcome to Yale Cancer Center answers with Dr. Ed Chu and Dr. Ken Miller. I am Bruce Barber. Dr. Chu is Deputy Director and Chief Of Medical Oncology at Yale Cancer Center and Dr. Miller is a Medical Oncologist specializing in pain and palliative care and he is the Director of the Connecticut Challenge Survivorship Clinic. If you would like to join the discussion you can contact the doctors directly, the address is canceranswers@yale.edu and the phone number is188-234-4YCC. This evening Dr. Chu speaks with Dr. Lindsay Harris and Dr. Gina Chung about new treatment options in breast cancer. Dr. Harris is the Director of the Yale cancer Center Breast Cancer Program and Dr. Chung is the Assistant Professor of Medical Oncology at Yale Cancer Center.
Chu
Lyndsay, lets start off with a brief overview. How
significant is breast cancer as a public health issue?
Harris
Unfortunately, breast cancer is a very common disease. We estimate
that if a woman lives to the age of 85 she has about a 1 in 8 risk
of developing breast cancer in her lifetime. About 200,000 or
more cases per year are diagnosed.
Chu
Wow, and in terms of cancer related mortality, how many deaths
would be attributed to this disease each year?
Harris
Fortunately those numbers have improved quite substantially and the
number of women who actually die from the disease is less than 30%
of the overall number of women who are diagnosed every year. At
least 70% of women with a breast cancer diagnosis are cured.
Chu
I gathered from some recent reports that in fact the survival
rates have actually improved over the last few years. Is that
correct?
Harris
That is absolutely right, and in fact, it appears that the survival
improvement is due not only to early detection and screening, but
also therapies that have been developed in the last 15 to 20 years
that have truly impacted survival.
Chu
A little later on in show we will get into more of these new target
therapies that have made a tremendous difference in treating women
with breast cancer. What age group do we tend to think about
for when breast cancer can develop?
Chung
Breast cancer is more common as we age. Although we all may know
of people who were diagnosed at a young age, it is typically
diagnosed more in the postmenopausal age groups, so 50+ and 60+.
However, we do know that breast cancer certainly can be diagnosed
earlier as well, and so screening is initiated earlier than the
postmenopausal age category.
Chu
How about if there is a strong family history of breast
cancer? Does
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breast cancer then typically occur at an earlier age in that setting, or it is still the same age risk?
Chung
We know family history is a very important risk factor for breast
cancer development, although, probably only about 10% or so of
breast cancer diagnoses are directly impacted by genetic risk
factors and a strong family history. It is clearly a very
important risk factor and in those women who are diagnosed with
breast cancer, and have very strong family histories, we do
advocate genetic counseling to assess what those risk factors are
more directly, and perhaps test for genes that may be involved.
Chu
What about some of the other risk factors in addition to
genetics?
Harris
As Gina has said, about 10% of women have a strong family history
of breast cancer, but there are other risk factors such as the age
when a women starts to menstruate; the earlier the age the higher
risk of breast cancer. The age at which she has her first
pregnancy and the length of her menses, in other words how long she
continues to menstruate until she goes through menopause, can be
risk factors.
Chu
When should women start getting mammograms, which is the gold
standard for this disease?
Chung
In this day and age screening mammograms are indeed still
considered the gold standard, although there is some controversy,
most people agree that screening should start for the typical
patient at 40, and annually thereafter.
Chu
And in those women who have a strong family history of breast
cancer, when would you suggest they start screening?
Chung
That varies, however, one of the things that we use as a rule of
thumb, is certainly if you have a family member that was diagnosed
with breast cancer at a very early age we say that screening for
other family member should begin approximately 10 years before the
age of which that patient was diagnosed. In addition to when
screening should start, perhaps other screening or newer screening
modalities should be considered such as breast MRIs.
Chu
On that point, there has been a lot made in the press about the
benefits of breast MRIs. What are your thoughts on that?
Chung
MRIs are a great tool, but for use with certain patients and
certain special circumstances. We are still beginning to try and
understand where and when we should implement it. As a
screening modality, the problem with MRIs is that they are very
sensitive, perhaps more sensitive than mammograms at detecting
small abnormalities; however, it may be a little too sensitive and
thus the risks of false
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positives are higher. At this point we try to limit use to those with the highest risk, but we are still trying to understand when to use it better.
Chu
Lyndsay, what about the issue of self-breast exams? When should
they begin and should women be educated and properly trained on how
best to do that?
Harris
Self-breast exams also represent an area of controversy. The
reason is that survival has not been definitively shown to be
improved by self-breast exam alone. The current
understanding, or recommendation, is that it is still very
important for a woman to understand the architecture of her
breast. We know as oncologists that many patients detect
their own breast cancers, and we also know that if done properly, a
woman can detect a change before her provider can detect it.
We currently recommend to all our patients that they do their
breast exams after their menses, usually a week or so after, and
that they get to know their breasts and do that at least on a
monthly basis.
Chu
And again when should that start?
Harris
As soon as the women develops breasts.
Chu
So that is pretty early on, in their teens?
Harris
Teenagers, yes.
Chu
What are some of the symptoms, or what should women look for when
they do their self-breast exams? What might be a harbinger for
breast cancer?
Chung
Certainly in younger women they naturally tend to have what we
call more lumpy breasts, so not every lump is necessarily a breast
cancer. But of course, as Lyndsay mentioned, it is very important
for a women to be familiar with the way her breasts normally feel,
and for younger women, how it may change throughout the menstrual
cycle. Typically a breast lump is considered something that could
be a harbinger for breast cancer, but there are other more subtle
changes that can signal something abnormal, like changes in the way
the skin looks and feels, a firmer texture, changes in the
way the nipple looks, sometimes it becomes more inverted and
pointing inwards and other subtle changes such as dimpling of the
skin.
Chu
Tenderness of the breast, should that be a cause for women to be
worried?
Chung
In general, breast cancer is not associated with a lot of breast
pain, but for certain types of breast cancers that could be one of
the findings.
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Chu
If a woman were to detect a new lump or mass, which is clearly
different, what should she then do?
Harris
She should examine the breast and check it again perhaps a few days
later. If it persists, she should see her family physician or
her gynecologist and ask them to do a breast exam.
Chu
And if they go to the family doctor or the GYN specialist, and they
confirm that there is a lump that is clearly different, what is the
next step?
Harris
Every women with a suspicious breast lump should have a mammogram,
typically if there is a palpable lump, if something can be felt, it
should also include an ultrasound examination.
Chu
Let us walk through that whole process. The ultrasound is done, and
indeed there is a mass there? What then happens?
Harris
What the specialists in breast radiology do is they look for
changes on the mammogram, shadows and calcifications that may
indicate the sign of malignancy. They also look for a solid
lump, not a cyst, but something that is solid. If any or both
of those signs are present, they would then do a biopsy.
Chu
And the biopsy is usually done by a surgeon who specializes in
breast disease.
Harris
Yeah, and either the surgeon or the radiologist can do the
biopsy. It is quite typical for radiology to do many of the
core biopsies now-a-days because they are the first people who
contact a woman who has a new breast abnormality.
Chu
One point to emphasize is that the radiology and the biopsy
procedures really should be done in a coordinating fashion by a
group of experts who specialize in breast disease.
Chung
I absolutely agree. Once a woman is diagnosed with breast cancer,
of course the treatment approach is a multimodality approach with
many different specialists involved in the management. It is
important to try to get them involved as early as possible.
Harris
We have surgical breast cancer oncologists who focus only on breast
cancer treatment. We have radiation oncologists who focus
only on breast cancer treatment and we have medical oncologists who
again, just treat breast cancer. In addition, we have
pathologists, radiologists and we have experts in lab medicine who
know specifically the details of breast cancer and this team comes
together to provide the best approach for an individual patient
with the diagnosis of breast cancer. As Gina pointed out, having a
specialist who does only breast cancer as
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their focus provides the optimal situation for a patient who can have a very serious health problem.
Chu
We would like to remind you to email your questions to canceranswers@yale.edu or
call 188-234-4YCC. At this time, we are going to take a short
break for medical minute. Please stay tune to learn more
information about breast cancer with our special guests, Dr.
Lyndsay Harris and Dr. Gina Chung.
Chu
Welcome back to Yale Cancer Center Answers. This is Dr. Ed
Chu and I am here in the studio this evening with my guests, Dr.
Lyndsay Harris and Gina Chung, both from the Yale Cancer Center
talking about the latest developments in breast cancer. Let's
switch gears a little bit and talk about the treatment of breast
cancer. Starting with you Gina, how do we approach the
treatment of breast cancer depending upon the individual
patient?
Chung
The treatment of breast cancer is of course dependent on a number
of factors that we call prognostic factors; most importantly, the
stage of the breast cancer, basically how big the tumor is and
whether there is involvement of the lymph nodes underneath the arm
and if there are any distant sites of cancer in the body.
This will dictate what kind of medications we would recommend to
the patient and whether chemotherapy, biologic therapies, hormonal
therapies, and even surgery and radiation may be offered to the
patient, but in general, it is usually a combination of surgery,
radiation, and medications.
Chu
If a woman has breast cancer that is localized to the breasts, is
it sufficient for that woman to just have surgery, plus or minus
lymph node dissection, and then followed with no further
treatment?
Chung
In a small proportion of patients it may be, but again, to stress
the importance of a
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multidisciplinary approach, now-a-days we are giving a lot of medications and radiation above and beyond just surgical resections. It is important for the patient to see specialists in other fields as well, to really understand what their risks are and to discuss the potential benefits and pros and cons of medications and radiation.
Chu
Lyndsay, one of the terms we hear about is adjuvant therapy;
adjuvant chemotherapy and adjuvant hormonal therapy. How do you
decide when to use that particular approach in a woman who has had
surgery and needs follow-up care?
Harris
As Gina has said, many woman are now receiving medication in
addition to the local therapy, surgery and radiation, and the
decision is really based on those features of the patient's breast
cancer, the size of the tumor, the lymph node involvement and also
specific markers in the tumor itself dictate which type of therapy
may be the best.
Chu
What type of markers do you look at specifically?
Harris
It is now standard of care to look at the estrogen receptor, the
progesterone receptor and the HER2 receptor on every breast cancer
that is diagnosed. Those markers tell us not only the
behavior of the tumor, but more importantly what the best therapy
for that particular patient is.
Chu
Are there any differences in the expression of those specific
markers, say in Caucasian women as opposed to African-American
women?
Harris
Yes, and the entire explanation for the disparity in survival
between African-American women and Caucasian women is not
understood, but part of the disparity may be due to the fact that
they have a more aggressive type of breast cancer. It is
typically what we call triple negative estrogen, progesterone and
HER2 receptor negative, and those tumors tend to be more
aggressive.
Chu
And obviously then the treatment strategy would be quite different
in that triple negative disease.
Harris
That is right. If a woman has the estrogen receptor she is
typically offered hormonal therapy such as tamoxifen and aromatase
inhibitor or a drug such as that. If she has HER2, she is
typically offered Herceptin as part of her adjuvant therapy or
therapy after surgery. However, if she has none of those
receptors we know that chemotherapy is actually more effective in
patients with triple negative tumors and they are very likely to be
offered chemotherapy as their adjuvant therapy of choice.
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Chu
Gina, you have been very actively involved in trying to understand
the process of angiogenesis and developing treatment strategies
that target that process. What is angiogenesis and what are some of
the strategies that you in particular have been focusing on?
Chung
Angiogenesis is the process of blood vessel growth. In simplified
forms for a tumor to grow beyond a certain size, let us say a few
millimeters, the hypothesis is that it needs new blood vessel
growth to supply the oxygen and nutrients to continue its growth
and spread. In the laboratory, there has been a lot of research
that confirms that this is a very important process in cancers and
breast cancers as well. Therefore, there has been a lot of research
recently looking at ways we can interrupt or inhibit this process
in the hopes that we can inhibit the growth of the tumor. We have
come a long way, for example, Avastin, which is an antibody similar
to Herceptin but it targets a molecule called vascular endothelial
growth factor or VEGF, has been shown to be effective in a variety
of cancers including breast cancers and is recently approved for
use in breast cancer and women with advanced breast cancer.
Chu
Which is really a very remarkable advance, certainly in the disease
that I know much better, which is colorectal cancer. That is where
Avastin was initially approved, but was then subsequently approved
for lung cancer and just within the last couple of weeks it has
been approved, as you said, for breast cancer. Now is it
approved for use as a single agent or to be used in combination
therapy?
Chung
The best and most optimal way of using Avastin is not entirely
clear yet, but the principle study that lead to its approval was a
large study in women with stage IV metastatic breast cancer who
were given this treatment as a part of their treatment program as
the initial treatment for their stage IV breast cancer. It involved
Avastin, plus a chemotherapy, in that instance Taxol, versus just
the chemotherapy Taxol alone, and it showed benefit above and
beyond chemotherapy alone. We try to develop clinical trials that
target multiple stages of breast cancer, but also subtypes of
breast cancer, and antiangiogenic agents are a very important part
of this program. For those with early-stage breast cancer, we
do have a clinical trial with preoperative therapy, which is before
surgery, and this involves giving Avastin plus letrozole, which is
a hormonal therapy, for about 4 months before surgery. This
way we can try to use a very exciting combination of medications to
shrink the tumor before the patient has surgery to optimize the
surgical result and also see the individual responses in the
patient. For those with metastatic or stage IV breast
cancers, we have several clinical trials including a drug called
sorafenib, which targets different important pathways including
angiogenesis pathways as well as other drugs important in the
angiogenesis process.
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Chu
You are also trying to develop what we call biomarkers of response
to these treatments that target angiogenesis. Can you tell us a
little bit about that as well?
Chung
Fortunately, for drugs like tamoxifen, hormonal therapy and even
Herceptin, we do have some measures of markers that we think can
predict whether a patient will have benefit with those drugs. For
example, if a woman has estrogen receptor expression, then those
are the patients that usually benefit from tamoxifen and it's
similar for HER2/neu expression and Herceptin. Unfortunately,
for the angiogenesis agents that are currently being studied, no
clear markers exist. This is very important because it allows us to
tailor the therapy most appropriately. It is very important
to try to develop markers both in tissue and other samples that can
help guide us in deciding which patients should get these
treatments. We do have several different important studies
built into the clinical trials both in tissue samples as well as in
blood that will hopefully allow us to better understand how these
agents work and to give us markers to predict response better.
Chu
Lyndsay, you have also been very actively involved in developing
clinical trials.
Harris
What we tried to do in the breast program is to provide clinical
trials for women at all stages of breast cancer and also different
subtypes of breast cancer. We have a portfolio of clinical trials
that address the HER2 positive type of breast cancer. We have
a group that targets the estrogen receptor positive group of breast
cancer and then we have a set of trials that target triple negative
breast cancer. We have specific trials that address each of
those different subgroups of breast cancer. Gina's entire
program, which is an angiogenesis based program, actually crosses
boundaries because it is effective in several different subtypes,
but we want to explore all different options for patients because
we do not know at this point what is going to be the best strategy
for women with breast cancer.
Chu
I understand you are the principal investigator of a large
cooperative group study that is being conducted called the ALTO
trial.
Harris
Yes, in the HER2 subgroup of breast cancer, we have several
clinical trials that focus on HER2 in the metastatic setting after
Herceptin and Tykerb have no longer continued to be
effective. We have a couple of trials that look at other
options for those patients including the drug rapamycin. In
the early stage setting, we have two preoperative trials that look
at new drugs for HER2 breast cancer, which include Tykerb or
lapatnib. We also have an opportunity in the adjuvant setting, the
ALTO trial, which has just been launched, which is a collaboration
between Europe, the United States and Canada. That trial is
for HER2 positive breast cancer patients who have completed their
local therapy. In the trial they would receive either Herceptin or
the drug lapatinib or Tykerb, which is the same drug just with a
different name, or a combination of the two. That trial is to see
what the optimal targeted therapy for HER2 positive breast cancer
patients is.
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Chu
What is great to see is that just within the last 3 to 5 years, we
have seen tremendous advances in the treatment of breast cancer and
it has become very individualized as to how we develop these
treatment strategies.
Harris
I completely agree with you. Having been in the field for about 15
to 20 years, I am gratified by the progress that we have made in
the improvement of survival, which I think is largely due to
targeted therapies.
Chu
Gina and Lyndsay, it has been great having you. It is amazing how
fast time has gone and we are at the end of the show. Thank you so
much for joining me this evening on Yale Cancer Center Answers.
Until next week, this is Dr. Ed Chu from the Yale Cancer Center
wishing you a safe and healthy week.
If you have questions, comments, or would like to subscribe to our podcast, go to yalecancercenter.org where you will also find transcripts of past broadcasts in written form. Next week, you will meet Dr. Fred Okuku, a fellow in medical oncology from Uganda.