Breast Cancer Awareness Month

October 12, 2020

October 11, 2020

Yale Cancer Center

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00:00Support for Yale Cancer Answers
00:02comes from AstraZeneca,
00:04the beyond pink campaign aims to empower
00:06metastatic breast cancer patients and
00:08their loved ones to learn more about their
00:11diagnosis and make informed decisions.
00:14Learn more at lifebeyondpink.com.
00:18Welcome to Yale Cancer Answers
00:20with your host
00:21Doctor Anees Chagpar.
00:23Yale Cancer Answers features the
00:25latest information on cancer care by
00:27welcoming oncologists and specialists
00:29who are on the forefront of the battle
00:32to fight cancer. This week, in honor
00:34of Breast Cancer Awareness Month
00:35it's a conversation about breast
00:37cancer with Doctor Lajos Pusztai.
00:39Doctor Pusztai is a professor
00:41of Medicine in medical oncology
00:43at the Yale School of Medicine,
00:45where doctor Chagpar is a
00:47professor of surgical oncology.
00:49Maybe we can
00:51start off by talking a little bit
00:54about breast cancer yesterday,
00:56today and tomorrow.
00:57Many of us,
00:58especially now in October are
01:00talking about breast cancer.
01:02It's certainly a very common malignancy,
01:04but tell us a little bit about
01:06how common it is and
01:09how deadly it is.
01:12I think it's most appropriate to
01:14start with the good news, the good
01:17news for breast cancer patients is
01:19that the survival rates have improved
01:22by 40 to 50% over the past 20 years.
01:25There are 50% more patients that survive
01:27breast cancer than 20 years ago.
01:29And about 85% of
01:31newly diagnosed breast cancer
01:33patients will never die from their disease,
01:35which we could paraphrase as being cured.
01:38The probability of survival of course,
01:40vary by stage.
01:41And in stage one breast cancer,
01:44which is the most frequently diagnosed
01:46stage of breast cancer due to the broadly
01:49availability of mammographic screening,
01:51the survival rates are
01:53even higher and above 90%.
01:55In Stage 4, disease
01:57survival still remains elusive,
01:58but patients live many years longer
02:01than they used to 20 years ago.
02:03Yeah, it's
02:04certainly good news,
02:05and I think that women now more and
02:09more are beginning to realize that
02:11just getting breast cancer
02:13is not a death sentence,
02:15but I want to take one step
02:17back and talk a little bit about
02:20something that you mentioned,
02:22which is how the survival rates
02:24have improved and one of the
02:26things that has helped in that
02:29is screening and in October
02:31we're all talking about, get
02:33your mammogram, get screened.
02:35Many women
02:38they'll come up to me
02:41and say I get my mammogram every
02:43year and I got breast cancer.
02:46Can you talk a little bit about
02:48the difference between screening
02:50or secondary prevention versus
02:52primary prevention?
02:55Yeah, so of course it's a shock
02:57for any individual to be diagnosed
03:00with cancer, but among Kansas,
03:02Briskin series is actually one of
03:04the most highly treatable and curable
03:07diseases and then a mammogram picks
03:09up cancer is actually a success of
03:12the mammographic screening story.
03:14So mammographic imaging is more
03:16sensitive than any self examination or
03:18physical examination by a physician,
03:20and the goal is to really find
03:23cancer as early as possible.
03:25Because the cure rates are
03:27directly proportional to the size
03:29and stage of the disease.
03:32And I think that this is a big
03:34difference that we see here in the
03:36Western World as as opposed to the
03:39developing world where mammographic
03:41screening isn't as widespread and
03:43many of those patients present late.
03:45But I want to pick up on something
03:47else that you just mentioned,
03:50which is to say the staging now
03:52Historically we always used to
03:54think about stage as being TNM.
03:56How big is the tumor?
03:58Has it gone to the lymph nodes?
04:00Has it spread
04:01outside of the breast,
04:03in the lymph node area to distant sites?
04:06Recently, however,
04:07there has been incorporated
04:09into the staging system,
04:10at least in the prognostic staging system,
04:14this concept of grade and receptor status.
04:17Can you talk a little bit about
04:20what those phenomena are and how
04:23they affect prognosis and stage?
04:26Yes, so staging this historically
04:29being a composite with the size of the
04:32cancer and the number of lymph nodes
04:35or being influence involved at all.
04:37Defining the classical anatomical stage.
04:39So we learned that there are many
04:42additional features beyond just the
04:44size of the tumor that determined the
04:47prognosis and increasingly the sensitivity
04:49of the cancer to various therapies.
04:52And these molecular variables or
04:54markers can really influence the
04:56overall prognosis of an individual.
04:58So staging is now really find by additional
05:02molecular variables in breast cancer,
05:04particularly grade and there stretching
05:06receptor status below grade Kansas.
05:08Even keeping the size the
05:10same do better than then,
05:12then higher grade terms and grade
05:14is A is a pathological variable
05:17that that sort of approximates how
05:20abnormal the cancer cells look.
05:23Do you struction Receptor Studies is also
05:26very important because we have highly
05:28effective estrogen targeted therapies
05:30that improve survival in these patients.
05:32So even with a longer term,
05:35their outcome actually is similar
05:37to what is smaller to me.
05:39Used to be many years ago which
05:42speaks to the efficiency of the novel
05:45therapies. Yeah, and just when we think
05:48about the landscape of all breast cancers,
05:51what proportion of breast cancers
05:53are hormone receptor? Positive.
05:56About 70% of all newly diagnosed
05:58breast cancer hormone receptor
06:00or estrogen receptor positive.
06:02This proportion does change the
06:05overage an it's even larger in the
06:08population who are above 6065 and
06:10somewhat less in younger patients.
06:13So in other words,
06:15patients in their 50s and 40s
06:17have a higher proportion of
06:20estrogen receptor negative
06:21breast cancers and the Epidemiology
06:24of breast cancer is such that.
06:27Age actually is a risk factor
06:29for developing breast cancer,
06:31so what's the average age at
06:33which women get breast cancer?
06:36So the average age is somewhere
06:39around between 60 and 65,
06:41so the majority of breast
06:43cancer patients are above 60.
06:45Which is plain to see risk
06:48insulin in in very young woman
06:50even their their early 30s.
06:52Yeah, so I think 2 two important points
06:55there. One is that breast cancer is a
06:58phenomena of aging and so women need
07:01to be aware of that as a risk factor.
07:04So many women asked me,
07:06you know why did I get breast cancer?
07:09I eat right? I exercise and you
07:11know the two main risk factors are
07:14being a woman and getting older.
07:17But as you say, lios,
07:18you know the other thing that's
07:21really important is that breast
07:22cancer can occur in young women and
07:25an they need to be aware of that.
07:27Let's let's go there for a minute
07:29and talk about younger women
07:31getting breast cancer,
07:32because certainly that's a
07:33shocking thing for many women.
07:35Some women are told that they are
07:37too young to get breast cancer and
07:39yet breast cancer seems to be more
07:41aggressive in the younger population.
07:43Key.
07:44Can you kinda talk a little bit about that?
07:48Yeah, so the risk factors for breast
07:51cancer also depend and vary by
07:54the molecular type of the disease,
07:56so the risk factors that increase the
07:59probability that someone would develop a
08:02nurse region positive breast cancer does
08:04include reproductive variables such as a.
08:07Having no children or having children
08:09late there is for estrogen receptor.
08:12Negative disease is very seem.
08:14Factors actually seemed to be protective.
08:18Another important risk factor is
08:20stretching exposure, and again,
08:21this is a risk factor for developing
08:24Australian receptive positive.
08:26This is and this has been clearly seen
08:28in the past when estrogen replacement
08:31therapy to treat for menopausal symptoms
08:35and with the hope that it would improve
08:38or reduce the risk of heart disease,
08:40has been widely followed.
08:42We saw an increase in estrogen
08:45receptor positive breast cancers.
08:47Other somewhat less important,
08:49but still significant risk factors
08:52include obesity or being overweight,
08:55especially if someone is postmenopausal,
08:57small amounts,
08:58but regular alcohol intake also increases
09:02the risk for breast cancer of both types.
09:07And I think the other
09:09risk factor,
09:11particularly for younger women,
09:12is genetics.
09:14A little bit about knowing
09:16your family history and some
09:18of the genetic mutations that
09:20can put women at risk,
09:22especially at a younger age.
09:25So the other important
09:28risk factor is indeed genetics
09:34and has someone inherited from
09:36their parents and particularly what
09:38sort of variance in these genes are
09:40present in an individual through
09:42through their parental lineage?
09:44There are genes which are associated
09:47with a very high risk of lifetime
09:50breast cancer and the most well
09:52known is of course
09:55BRCA1 and BRCA2 genes, which,
09:57if they carry a mutation
10:00that someone has inherited
10:03the lifetime risk can be
10:06as high as 50 to 80% to develop
10:09breast cancer and other cancers
10:11unfortunately as well,
10:12such as ovarian cancer or male patients
10:15remain at risk for prostate cancer.
10:18Pancreatic cancer.
10:19There are other genetic causes
10:21of breast cancer
10:22that are much rarer than the BRCA gene
10:26mutations and these include genes like P53
10:29Check one, ATM mutations.
10:33But even combined,
10:36these only account for probably
10:38about 10% of early onset breast cancer.
10:41The remaining 90% of patients
10:43with an early onset breast cancer
10:45carries some other type of abnormality
10:47that they likely inherited.
10:49But we don't really know what they are.
10:53They very likely are not a single gene,
10:55but multiple genes together
10:57that together increase the risk.
10:59But the good news is that death
11:01risk is relatively small.
11:04It's nowhere close
11:05to these 50 to 80% risk of
11:08developing cancer during their lifetime,
11:09so a strong family history in the
11:11absence of this detectable germline
11:13mutations still carries an increased risk.
11:16But that risk is more like 20-30%
11:18above the average risk that
11:21would affect an individual who
11:23has no family history.
11:24And the other interesting
11:26thing and something
11:27I think that many of our listeners may
11:30not know, and many patients
11:33have told me is surprising to them,
11:35is that the vast majority of women
11:37who get breast cancer actually
11:39don't have a family history?
11:41You want to talk a little bit about that.
11:46Yeah, that's correct and it
11:48relates to aging being the
11:51most significant risk
11:53factor for breast cancer.
11:55Also for many other cancers and
11:58in fact many other diseases,
12:00it's probably a consequence of
12:02simply the aging process that
12:04actually damaged various
12:06cells throughout our body.
12:08And if this damage reaches a threshold
12:11purely through bad luck,
12:13then a cell transitions into
12:16a malignant or cancerous
12:18phenotype and then goes
12:20down the path of becoming cancer.
12:23Yeah, one other topic
12:25I want to touch on before we
12:29leave this whole concept of genetics
12:32ties into some of the subtypes
12:35that you were talking about earlier.
12:38When we think about subtypes
12:40of breast cancer
12:41oftentimes we talk about whether
12:44these are estrogen receptor
12:45positive, progesterone receptor
12:47positive or HER2 positive so
12:50these three markers help us to understand
12:53different types and so are people
12:56who have a genetic predisposition,
12:58for example, BRCA one or two,
13:02are they more at risk of certain
13:05subtypes of breast cancer than others?
13:09Yes, the BRCA mutation
13:12increases the risk of
13:14triple negative breast cancer
13:16more than it increases the risk
13:18for the EGFR disease.
13:20In other words,
13:21patients with the BRCA1 or 2
13:23mutation more frequently have
13:25estrogen receptor negative or estrogen
13:28and HER2 receptor negative,
13:30what we call triple negative
13:32disease in the BRCA2 Mutation.
13:35This proportion is closer to 50-50.
13:42To give some additional background into
13:44this receptor categorization,
13:46one of the most important insights
13:49that we have made into the biology
13:51of breast cancer in the past 20
13:54years is the recognition that the ER
13:57positive or estrogen receptor positive
13:59breast cancer really fundamentally is
14:01different from the triple negative or ER
14:03negative cancers.
14:03They arise from different
14:05cells in the breast.
14:06They have different risk factors
14:08and they require different
14:10therapies.
14:13There is a good marker that we
14:16routinely test for, so estrogen receptor
14:19and progesterone receptor and HER2 which
14:23is an abbreviation for the human
14:26epidermal growth factor receptor 2 gene.
14:29So HER2 is the third variable that we
14:32always test the breast cancer for because
14:35there are highly effective therapies for
14:37this particular molecular abnormality,
14:40but about 10 to 15% of cancer carry it.
14:43I think that that's so important
14:46to really understand that classification,
14:49which we're going to get into right after
14:52we take a short break for a medical minute.
14:56Please stay tuned to learn more
14:58about the treatment and diagnosis of
15:00breast cancer with my guest doctor Lajos Pusztai.
15:03Support for Yale Cancer Answers
15:05comes from AstraZeneca, proud partner
15:07in personalized medicine developing
15:09tailored treatments for cancer patients.
15:12Learn more at astrazeneca-us.com.
15:15This is a medical minute about lung cancer.
15:18More than 85% of lung cancer diagnosis
15:21are related to smoking and quitting even
15:24after decades of use can significantly
15:27reduce your risk of developing lung
15:29cancer. For lung cancer patients
15:31clinical trials are currently underway
15:33to test innovative new treatments.
15:35Advances are being made by utilizing
15:38targeted therapies and immunotherapies.
15:40The BATTLE 2 trial aims to learn
15:42if a drug or combination of drugs
15:45based on personal biomarkers can help
15:47to control NSCLC.
15:50More information is available
15:53at yalecancercenter.org.
15:54You're listening to Connecticut public radio.
15:59Welcome
15:59back to Yale Cancer Answers.
16:01This is doctor Anees Chagpar
16:03and I'm joined tonight by
16:05my guest Doctor Lajos Pusztai.
16:08We're talking about the care of
16:10patients with breast cancer in
16:12honor of Breast Cancer Awareness
16:14Month and right before the break
16:17we were talking a little bit
16:19about these types of breast cancer.
16:21This classification based on receptors.
16:23the ER, the PR,
16:24the HER 2 neu and you were
16:27telling us that
16:30these make a big difference in terms of a
16:33patient's prognosis and their treatment.
16:36So let's pick up our conversation there.
16:40Tell us a bit more about the risk factors
16:43for each of these different types of cancer.
16:48How you think about them,
16:50and how that really dictates treatment.
16:54Risk factors for ER positive disease
16:58is being overweight or obesity
17:00at the post menopausal state.
17:03Also regular alcohol intake
17:06increases the risk a little bit also.
17:16Starting regular periods at
17:18a young age and having a late
17:22menopause are also associated with
17:24increased risk as well as late
17:27childbirth or lack of pregnancy.
17:30So these reproductive variables or
17:32reproductive sort of factors don't
17:35seem to carry the same weight.
17:37For ER negative disease,
17:42actually multiple early pregnancies
17:44seem to increase the risk and
17:47lack of breastfeeding.
17:48With regards to therapy
17:51though there are really large
17:53differences in how we approach
17:56different types of breast cancers.
17:59Yeah, tell us more about that.
18:01With ER positive disease,
18:03the most important set of
18:05weapons in our armamentarium is
18:08estrogen stretching therapy and this could
18:11include drugs which block the effect
18:13of estrogen and also drugs which could
18:16block the enzymes that make estrogen
18:18and lowers region levels so these are
18:21called aromatase inhibitors and they
18:23are the mainstay of curative treatment
18:26for early stage ER positive disease.
18:30We used to recommended these drugs
18:33be taken for five years,
18:34but there is more and more data that
18:37suggests that going beyond five years,
18:39an extended duration of this so called
18:42adjuvant endocrine therapy to 10 years
18:44further improves the chance of
18:47cure and reduces the risk of recurrence.
18:49Literally a few days ago there was
18:52another major breakthrough announced
18:54in the news and the results of the
18:57clinical trial will be presented
18:59shortly adding another additional
19:03drug to this
19:05class of agents could further improve
19:08the survival rate in early stage disease.
19:10This additional type of drug
19:12is called the CD K46 Inhibitor.
19:15These are drugs that we have
19:17been using for many years
19:19in the incurable metastatic setting,
19:21because they prolong the life of
19:23patients with metastatic disease.
19:25And now we have data that shows
19:27that it actually improves cure
19:29rates in early stage disease.
19:31So this is going to be another major
19:33new development that will come to the
19:36clinic later this year and definitely
19:39early next year.
19:41Does that mean that patients who are taking this
19:43endocrine therapy this pill that
19:45people take for breast cancer for
19:47five years and now for 10 years might
19:50be getting another pill to take?
19:52Yes.
19:58And when we talk on this show,
20:00about personalized
20:03medicine and targeted therapies,
20:05it seems to me that that was probably one
20:07of the earliest targeted therapies was
20:10really targeting the estrogen receptor,
20:13but many patients want to know will they
20:16still need chemotherapy if their cancer
20:18is an estrogen receptor positive cancer?
20:21Are there a subset of patients in whom you
20:24would still offer chemotherapy in addition,
20:27and how do you make those decisions?
20:31So a few years ago and this used
20:34to be a constant topic of discussion
20:36among physicians and part of the
20:40multidisciplinary tumor board discussions.
20:42But in the past few years,
20:45we actually have more molecluar tests
20:47that make this discussion
20:50more objective than the subjective
20:52feeling of the physician.
20:54So there are a number of molecular
20:57tests that can be performed on the
20:59resected tumor issue or on a biopsy
21:02of the cancer that established
21:04diagnosis which could help define
21:07to what extent a particular patient would
21:09benefit from adjuvant chemotherapy
21:11in addition to the hormonal therapy.
21:14These tests have various commercial
21:16names and they are provided by various companies.
21:25They all invalidated for the same purpose
21:28that they can define the ER positive
21:31or estrogen receptor positive
21:33population that benefits from adjuvant
21:36chemotherapy.
21:38We also learned that the majority
21:40of the esgrogen and receptor positive
21:43patients do not need chemotherapy.
21:45But if the assay predicts that
21:48they do need chemotherapy,
21:49it's important that they they understand
21:52the consequences and the fact that this
21:54could improve cure rates.
21:56So for all of our patients
21:59who are listening out there,
22:01and many of them may
22:03either have had breast cancer
22:06themselves or know somebody who has.
22:09Should all patients who have
22:11estrogen receptor positive cancers
22:13be advocating for themselves to
22:15get one of these molecular assays?
22:18Or are these assays something that
22:21we will order in specific patients?
22:26It's probably not the best
22:28way to do this in everybody
22:31but rather in patients where the
22:34question whether chemotherapy
22:36could help or not is uncertain.
22:39There are clinical situations where
22:42a physician can quite confidently
22:45feel that the chemotherapy wouldn't
22:46be helpful or would be necessary
22:49if it is a very large tumor
22:51with multiple influences involved,
22:53it would be risky to avoid chemotherapy,
22:55and regardless of the results,
22:57because even with this small chance
22:59or a small relative improvement could
23:02translate into a significant number of
23:04patients who benefit when the risk is
23:06very high and the flip side of this,
23:09there are very small,
23:10very low grade or grade one tumors
23:12less than a centimeter,
23:15there is no lymph node involvement where
23:17it's also clear that the added benefit
23:20from chemotherapy could be very
23:22very small because the chance
23:23of cure with surgery alone,
23:25plus with hormone therapy,
23:26is already very high.
23:28So we tend to use these tests
23:30instead of this middle ground setting
23:33when the risk for recurrence is
23:35very low nor very high.
23:37Now to move to
23:39the other kind of types of
23:41breast cancer and other types
23:43of therapy you had mentioned.
23:45This other receptor HER2
23:47and the fact that we have targeted
23:49therapies for this as well that
23:52are very efficacious.
23:57HER 2 positive breast cancers
23:59became the poster child of our
24:02success in breast cancer treatment.
24:04This came about by the discovery
24:06of antibodies and drugs
24:08that block the effect of this
24:11HER 2 signaling to
24:14amplify breast cancers.
24:16About 10-15 years ago and now we have
24:18at least four or five different
24:21HER2 targeted therapies that can
24:24be combined with standard of care,
24:26hormonal therapy,
24:27or chemotherapy if chemotherapy is needed,
24:29which improves the efficacy of these
24:32more conventional treatment modalities.
24:34Leading to very,
24:35very high rates of cure,
24:38avoiding recurrences in HER 2
24:41positive disease.
24:44How do patients
24:47decide with their doctor about which
24:50of those therapies is optimal?
24:56Herceptin is
24:59always part of the therapy of HER 2
25:02positive patients either combined
25:04with chemotherapy and following the
25:07completion of chemotherapy to complete
25:09one year on this particular drug,
25:11Herceptin, but also we often add
25:14another drug called pertuzumab
25:16which increases the efficacy and
25:18combined with chemotherapy,
25:21but also with hormonal therapy.
25:25We also learned that the strategy also
25:27matters, how we sequence the different
25:29types of treatments that someone needs
25:32to ensure or maximize the chance of cure
25:35to clearly patients who need surgery
25:37also need systemic therapies
25:39that get to every part of the body with
25:42the goal of eradicating micrometastatic
25:44cancer cells or cancer cells that have
25:47left the breast and hide somewhere
25:49in the body before the surgery
25:53to remove the tumor.
25:55So it turns out that for HER 2
25:58positive disease,
25:59probably the most effective strategy
26:01is to start with a systemic therapy.
26:04Often times with chemotherapy,
26:06because by following this strategy
26:09one could assess how effective
26:11the treatment was at the time of
26:13the surgery and up to 60-70,
26:15or even 80% of the time
26:18patients may have no cancer left in
26:20their breast by the time they finish
26:23their preoperative chemotherapy.
26:25With HER2 targeted regiment
26:27and those patients do really well,
26:29but importantly for those patients whose
26:32cancer survives at least to some extent,
26:35the preoperative treatment we have
26:37Plan B or back of options that have
26:40been shown to improve their survival,
26:42and these are also HER 2
26:45targeted drugs,
26:46but with some extra strength added to them,
26:49implying that there is additional
26:51chemotherapy component attached to HER 2
26:54antibody or the entire antibody.
26:57So one question that patients
26:59may ask is why not give them the
27:02supercharged HER 2 therapy,
27:04the backup drug up front?
27:07It's a good question and in fact
27:09it turns out that
27:11the supercharged HER 2 targeted
27:13antibody is still not as good as
27:16the chemotherapy plus Herceptin
27:18plus together, in other words
27:20this pathological complete
27:22eradication of the cancer is a little
27:25less if you just use one drug.
27:27This supercharged Herceptin.
27:28Which is called TDM one.
27:32So that's the reason why.
27:34But we also know that it works
27:37even on cancer cells that survived the
27:41more sort of aggressive initial therapy.
27:44And that's
27:45the main reason why it's sequenced this way,
27:49And so the final kind of category
27:52of patients are ones that
27:54really don't express estrogen
27:56receptor progesterone receptors.
27:58So endocrine therapies are
28:00not particularly effective.
28:02They don't have
28:03HER 2 positive cancers,
28:05so these anti HER 2 agents
28:08aren't particularly effective,
28:09and that's really this triple
28:11negative breast cancer class.
28:13So what's your approach there?
28:16In triple negative disease,
28:17particularly for early stage patients,
28:19which is about 90% of all newly
28:22diagnosed triple negative breast
28:24cancers are at early stage, stage
28:26one, stage two, stage three disease,
28:29we haven't really had any major
28:31breakthroughs for about 20 years
28:34until literally last
28:36year and earlier this year,
28:39when a number of clinical trials
28:41have shown the efficacy of
28:43chemotherapy could be increased
28:44by including immune checkpoint
28:46inhibitors so the immune checkpoint
28:48innovators had a new class of drugs,
28:51which stimulates or Rev up
28:53the anti cancer immune response and
28:55they have been shown to be highly
28:58effective in some very difficult
29:00to treat cancers like lung cancer,
29:03Melanoma and now we have evidence
29:05they also work in early stage,
29:08triple negative disease and also
29:10in combination with chemotherapy.
29:11They have shown to prolong the life of
29:15patients with advanced or stage four,
29:17triple negative cancer.
29:19So these are the most important
29:21recent advances in the management
29:23of triple negative
29:25disease.
29:26Dr. Lajos Pusztai as a professor of Medicine and medical
29:29oncology at the Yale School of Medicine.
29:32If you have questions,
29:34the address is canceranswers@yale.edu.
29:36And past editions of the program
29:38are available in audio and written
29:40form at Yalecancercenter.org.
29:41We hope you'll join us next week to
29:43learn more about the fight against
29:46cancer here on Connecticut public radio.