Breast Cancer Awareness Month: Progress in Metastatic Breast Cancer Research & Treatment

Name: Breast Cancer Awareness Month: Progress in Metastatic Breast Cancer Research & Treatment
Uploaded: 2025-10-30T15:13:12.4Z
Duration: 58 min 36 s

October 30, 2025

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00:01I'm doctor Miriam Lustberg,
00:03and I'm joined today by
00:05two colleagues
00:07from the Yale Breast Program,
00:10doctor Sarah Shellhorn
00:12and doctor Dan O'Neil.
00:14We are all breast oncologists,
00:17and we will be focusing
00:19on today
00:20on all aspects of metastatic
00:23breast cancer,
00:24in terms of systemic therapies,
00:27what are we currently using
00:29in the clinic as well
00:30as clinical trials as well
00:32as some of the,
00:34newer emerging,
00:35therapies.
00:37There will be ample time
00:38for questions.
00:39So as you think of
00:40questions, feel free to
00:42put them in the in
00:44the q and a portion,
00:46of the portal,
00:47and we should have,
00:50time to to get to
00:51to most of your questions.
00:54So,
00:55so so the focus tonight,
00:58is is, as I mentioned,
00:59on metastatic breast cancer,
01:01where the primary,
01:04most effective therapy is a
01:05systemic therapy. So we'll be
01:07talking about the different subtypes
01:09of breast cancer
01:10and,
01:11what the different
01:13management strategies are.
01:15With that, I will turn
01:17it over to doctor Sarah
01:18Schallhorn.
01:21Thank you, Mariam, and welcome
01:23to everybody. I'm delighted to
01:25be here tonight. I just
01:26took a quick peek over
01:28at the attendee list, and
01:29I see some familiar faces.
01:31So for those of you
01:32I know, welcome. And for
01:33those of you that I
01:34don't know,
01:35welcome.
01:37But,
01:38doctor O'Neil and I have
01:40divided up our time. We
01:42were asked to prepare
01:44ten to fifteen minutes of
01:46of information about metastatic
01:48breast cancer. And so we
01:50divided that in into two
01:52groups, and I'll be discussing
01:53primarily
01:55two subtypes of breast cancer,
01:57HER2 positive and triple negative
01:59metastatic breast cancer.
02:01And doctor O'Neil will be
02:02taking on the
02:04the huge topic of hormone
02:05receptor positive breast cancer.
02:08And
02:09this is easily
02:11this this topic could easily
02:13take up several hours.
02:16We could we could wax
02:17poetic for a really long
02:19time.
02:20So trying to condense this
02:22to just ten to fifteen
02:23minutes was a challenge.
02:26But we we will give
02:27it a try.
02:28So very, very quickly, what
02:31is metastatic breast cancer?
02:33As many of you likely
02:35know, it's cancer that started
02:37in the breasts.
02:38And and when cancer starts
02:40in the breasts, it starts
02:42to develop
02:43two basic characteristics
02:45that make cancer cancer.
02:47One of them
02:48is the ability to grow
02:50without any
03:03a
03:06start to form cancer,
03:08that stays within the breast
03:10and stays within the lobes
03:12or the ducts of the
03:13breast.
03:14Then they can become
03:15invasive
03:17and develop
03:18into metastatic disease. When those
03:20cancer cells invade, they break
03:23through the lining of the
03:24duct or the lobe,
03:27and start to invade into
03:29either the bloodstream or the
03:31lymphatics
03:32and travel to other parts
03:34of the body.
03:35So the definition of metastatic
03:37breast cancer is
03:38breast cancer cells that have
03:40traveled to another part of
03:42the body. And the most
03:43common places for breast cancer
03:45to go are the lung,
03:47the liver, and the bones
03:49with a fourth
03:51most common location
03:52being the brain.
03:55And when we think about
03:57how metastatic breast cancer is
03:59treated,
04:01we first look at
04:03three different proteins. We look
04:05at the estrogen receptor, the
04:07progesterone
04:08receptor, and a protein called
04:10HER2,
04:11on every breast cancer
04:13specimen. So the pathologist
04:15looks at a biopsy specimen,
04:18looks at these cells under
04:19the microscope, and measures the
04:21amount
04:22of estrogen receptor and progesterone
04:24receptor and then a protein
04:26called HER2. We'll talk about
04:27it in a second.
04:28And,
04:30I'm I'm gonna leave a
04:31little of this for doctor
04:32O'Neil, but estrogen and progesterone
04:34are female hormones
04:36that even
04:38after menopause are circulating in
04:40in some level in the
04:41bloodstream.
04:42And the presence of the
04:44estrogen receptor and presence of
04:45the progesterone
04:46receptor on a cancer cell
04:49means
04:50that that cancer cell is
04:51fueled
04:52at least in part
04:54by those hormones. So cancers
04:56that have the estrogen and
04:58or progesterone receptor are hormone
05:00receptor positive
05:02and tend to respond to
05:05anti hormone types of treatment.
05:07So that's the sub the
05:08subject of doctor O'Neil's
05:10whole spiel, which we'll get
05:11to in a second.
05:14The the third protein that
05:15we look for is a
05:17protein called HER2.
05:19And HER2 is a protein
05:22that sits on the surface
05:23of cancer cells,
05:25and
05:26it's there in low numbers
05:28normally, but sometimes it can
05:30be present in
05:31in higher levels.
05:34And when it's present in
05:35higher levels, that can be
05:37the driving force for cancer.
05:39So lots of HER2
05:41can make those cancer cells
05:43want to grow faster,
05:45and spread quicker.
05:49And so,
05:53the topic of my portion
05:55of this program is is
05:57HER2 positive breast cancers
06:00and then another subtype
06:03called triple negative breast cancer.
06:05And so we talked about
06:07the three different receptors that
06:08we check, the estrogen receptor,
06:10the progesterone receptor, and then
06:12this protein called HER2. And
06:14when the cancer cells do
06:15not have any of those
06:17three proteins, that's one, two,
06:19three proteins that are negative,
06:21it's where we get the
06:22title or the name triple
06:24negative breast cancer.
06:26So I'm gonna first start
06:27with triple negative breast cancer.
06:31These aren't cancers that are
06:32fueled by
06:34hormones. They are not
06:36fueled by having extra amounts
06:38of HER2.
06:39And, unfortunately,
06:41that means that the mainstay
06:43of treatment
06:44is chemotherapy
06:45drugs.
06:46And these are chemotherapy drugs
06:47that are generally given through,
06:50through the vein in an
06:51intravenous fashion.
06:53And these drugs go everywhere
06:55in the body
06:56with the idea of trying
06:58to kill cancer cells wherever
07:00they might be. And we
07:02have lots and lots of
07:03chemo drugs that work in
07:05breast cancer and in in
07:06triple negative breast cancer,
07:10but they have lots of
07:11side effects. This is one
07:12of the big problems with
07:13chemotherapy. It can affect almost
07:15every organ system in the
07:17body from the brain all
07:19the way to the muscles,
07:20from the lungs to the
07:22genitourinary
07:23system.
07:24Any part of the body
07:26can be affected by by
07:27chemotherapy
07:28because it's not particularly specific.
07:31It doesn't
07:32target anything.
07:34It really affects any cell
07:36that's growing,
07:38and that can be normal
07:39cells like the lining of
07:40the gut,
07:41normal cells like they're in
07:43the skin,
07:45normal cells anywhere.
07:48Furthermore, chemotherapy has even more
07:51downsides. It's inconvenient.
07:53It requires frequent visits to
07:55clinic and to infusion.
07:57This can impact things,
07:59that are really important in
08:01a woman's life, like
08:03child care, trying to arrange
08:05transportation.
08:07These drugs are generally intravenous,
08:09which means that that
08:11getting an IV over time
08:13can be more and more
08:14challenging. Because every time you
08:16put an IV in, you
08:17create a little bit of
08:18scar tissue.
08:20It can lead to loss
08:21of work productivity, which can
08:23cause what we call financial
08:24toxicity or financial harm to
08:27people who have to deal
08:28with chemotherapy over the long
08:29term. And it can have
08:31tremendous effects on on a
08:32woman's mental health.
08:34In fact, this is work
08:36that I did a number
08:37of years ago.
08:39Not just physical concerns,
08:41impact people,
08:43getting
08:44getting chemotherapy. And when we
08:46showed that almost half of
08:47patients or over half of
08:48patients have more concerns with
08:50things that aren't physical.
08:55So I apologize if this
08:57feels a little bit choppy
08:58because it is. There's just
08:59a lot to say here.
09:01Some of the most exciting,
09:04drugs that we're using now
09:06belong to a class of
09:08medicines called antibody drug conjugates.
09:11So we talked a little
09:12bit about the fact that
09:13chemotherapy
09:14is,
09:17it targets
09:19all different types of cells
09:20regardless of where they are.
09:22But antibody drug conjugates,
09:24I'd like to think of
09:25them more like tumor seeking
09:27missiles.
09:28So there's been a lot
09:29of talk about antibodies over
09:30the last five years since
09:31the the start of the
09:32COVID pandemic, but antibodies
09:36are proteins
09:37created by
09:39by lymphocytes
09:40in part of the immune
09:42system.
09:43But we can create
09:45antibodies in the lab. These
09:47are called monoclonal antibodies, and
09:48they they basically are like
09:50targets for particular proteins. So
09:52you have an antibody to
09:53a particular
09:54protein.
09:55And so
09:58what an antibody drug conjugate
10:00is
10:01is an antibody that's targeting
10:03a protein
10:04on the cancer cell. And
10:06riding along with it, attached
10:08to the antibody,
10:10is a chemotherapy drug. We
10:12call that the payload.
10:14The chemotherapy drug is riding
10:15along with the antibody. So
10:16the antibody finds the tumor.
10:18It finds the protein that
10:20it's looking for. It binds
10:21to that protein, and it
10:22delivers
10:24the chemotherapy
10:25directly to the tumor. And
10:27there are a few different
10:28antibody drug conjugates that have
10:30come come about over the
10:31last five, ten years, and
10:33we'll talk about
10:35most of them here.
10:37The second class of medicines
10:39that's used in triple negative
10:41breast cancer
10:43is immunotherapy.
10:44And immunotherapy,
10:47targets
10:48the
10:49immune system. And more
10:51appropriately, it actually takes the
10:53brakes off the immune system.
10:55So in the presence of
10:56cancer,
10:58the immune system kinda says,
10:59well, that that looks a
11:01little bit like me. It
11:02looks a little bit like
11:03self.
11:04I'm gonna back off.
11:06So the cancer cell kind
11:07of
11:08puts the brakes on the
11:09immune system, not allowing the
11:11immune system to fight the
11:12cancer.
11:13But immunotherapies
11:15like Keytruda,
11:17probably the one we use
11:18most commonly in breast cancer,
11:20but there are others used
11:21in other types of cancers,
11:24works to take the brakes
11:25off the immune system. So
11:27it allows,
11:29a person's a patient's body,
11:31a patient's own immune system
11:33to help fight the cancer.
11:34And that reactivates the immune
11:36system so that in combination
11:39with chemotherapy,
11:41the the immune system can
11:43then fight the cancer and
11:45get a more robust response.
11:47So immunotherapy
11:49is another class of medicines
11:50that we use primarily in
11:52triple negative breast cancer.
11:54And finally,
11:56another target that's that's applicable
11:59for
12:00several
12:01types of breast cancer, but
12:02those particularly
12:04associated with BRCA one and
12:07BRCA
12:08two mutations.
12:10These are called PARP inhibitors.
12:12And it has to do
12:13PARP inhibitors have to do
12:15with
12:16normal cell division. And and
12:19people who have these types
12:21of mutations
12:22in in BRCA one and
12:23BRCA two,
12:26in the normal process of
12:28cell division,
12:30they make mistakes.
12:32They make more mistakes than
12:33than
12:34is usual. And when those
12:36mistakes happen in the normal
12:37process of cell division,
12:39cancers are much more likely.
12:43The the
12:45PARP inhibitor,
12:47well, actually, people with these
12:48mutations aren't able to
12:51repair those mistakes in as
12:53an efficient way as someone
12:55who who doesn't have those
12:56mutations. And PARP inhibitors
12:59work,
13:00by preventing
13:02repair
13:03and
13:04basically lead these cells to
13:05commit suicide. So PARP inhibitors
13:07are pills that we use
13:09fairly frequently in people that
13:10have these types of mutations.
13:13So moving very quickly to
13:16HER2 positive breast cancer.
13:18So remember, HER2 is a
13:20protein that's on the surface
13:22of cancer cells. And when
13:23HER2 is there in high
13:24levels or it's overexpressed,
13:27that leads that's the the
13:29primary driver for growth of
13:31those cancer cells.
13:34And up until maybe twenty
13:36five ish years ago, this
13:38was really bad because HER2
13:41positive breast cancers,
13:43were very aggressive. They had
13:45high high likelihood of developing
13:47into metastatic disease and high
13:49likelihoods of going to going
13:51to
13:52major organs like the liver
13:54and the brain.
13:56But at again, about two
13:58and a half decades ago,
14:00the drug trastuzumab
14:02or Herceptin was developed, and
14:04it revolutionized the treatment of
14:06of metastatic breast cancer first
14:08and and then earlier stage
14:10breast cancers a little bit
14:11later.
14:13And that began,
14:15a long history of targeting
14:18HER2,
14:19first with trastuzumab
14:21and then later with additional
14:24antibody drug conjugates, other monoclonal
14:26antibodies, and
14:28oral medications called tyrosine kinase
14:31inhibitors.
14:32This is just the history
14:33of HER2 positive breast cancer
14:36way back to nineteen thirty
14:38five, and not a whole
14:39lot happened between nineteen thirty
14:41five until nineteen until the
14:43nineteen nineties. But starting in
14:45nineteen ninety eight when trastuzumab
14:47came about,
14:48there have been
14:49many, many drugs that have
14:51been approved in various settings.
14:54Lapatinib, pertuzumab,
14:56a drug called TDM one
14:57or Kadcyla,
14:59neratinib or new NERLYNX,
15:02pirotinib,
15:03tucatinib, neratinib, margetuximab,
15:05all of these drugs have
15:06come about over just the
15:08last decade or so,
15:10in
15:11for patients with HER2 positive
15:13breast cancer. So really quickly,
15:17HER2 positive
15:20breast cancer is primarily treated
15:22first with HER2 antibodies,
15:25primarily trastuzumab and pertuzumab, which
15:27target that HER2 receptor. And
15:29these can be administered either
15:31via infusion or a shot.
15:35And they're often used together
15:37because they block HER2
15:39in in complementary ways.
15:41Then there are oral HER2
15:42drugs like lapatinib,
15:44neratinib, tucatinib.
15:46Sometimes I wonder who actually
15:48names these medications. There's a
15:49lot of vowels there. These
15:50are hard to
15:51say.
15:53But these medications
15:55block the intracellular
15:57signaling that comes from the
15:59HER2 receptor
16:00leading to cell growth.
16:01And then finally,
16:03antibody drug conjugates,
16:05the tumor targeting
16:07missiles.
16:08They have a a place
16:10in
16:11the treatment of HER2 positive
16:13breast cancer too. In fact,
16:15the two most common,
16:17antibody drug conjugates
16:19are HER2 targeting antibody drug
16:21conjugates.
16:24The the latest
16:25antibody drug conjugate to come
16:27through the pipeline is a
16:28drug called nHER2,
16:30which is trastuzumab
16:32antibody
16:33targeting HER2
16:35coupled
16:36with a a chemotherapy
16:38called Dirextican.
16:41Another antibody drug conjugate called
16:44Kadcyla or trastuzumab
16:47tansine is that Herceptin antibody
16:50coupled to,
16:52a chemotherapy called m tansine.
16:55And
16:56these two drugs have not
16:58only,
17:00provided us with two additional
17:01treatments
17:05data coming out just in
17:08June of this year looking
17:10at,
17:11trastuzumab, daroxetacaner,
17:13and HER2
17:14in the first line setting
17:16for people with metastatic HER2
17:17positive breast cancer.
17:20Occasionally, we we also use
17:23chemotherapy
17:24in HER2 positive disease,
17:27combined with trastuzumab.
17:30And then for patients that
17:32have HER2 positive and also
17:34hormone receptor positive breast cancer,
17:36we also use endocrine therapy.
17:40I'm I know I've already
17:41gone over the time that
17:43I said that I would
17:43take,
17:45but I wanna just mention
17:48the way that new drugs
17:51come up and they get
17:53approved by the FDA is
17:55through a series of clinical
17:57trials.
17:58And clinical trials
18:00require patients. This is how
18:02we determine
18:03whether a drug is effective
18:05or not, and we look
18:06at new combinations of drugs
18:07and compare them to to
18:09older combinations. It's how we
18:11move the field forward.
18:13Clinical
18:14trials, could also be called
18:15clinical studies, studies, research trials,
18:18protocols.
18:20But a clinical trial
18:23is,
18:24more than just
18:26a lab test or a
18:27test on a guinea pig.
18:29Clinical
18:30clinical trials,
18:32afford patients an opportunity
18:34to contribute to the field
18:36and potentially get highly effective
18:38therapy even before it's approved.
18:41There are lots of phases
18:42of clinical trials starting at
18:44the earliest phases where we're
18:46we're studying new drugs or
18:47new combinations of drugs and
18:49looking
18:50at at toxicities
18:51all the way to phase
18:53three clinical trials, which are
18:55are usually
18:56randomized
18:57clinical trials where there are
18:58multiple arms,
19:01of the trial,
19:03and even phase four clinical
19:05trials, which which happen
19:07after a drug is approved.
19:13And the the likelihood
19:14that a drug becomes FDA
19:16approved
19:17go gets lower and lower
19:18the the later the phase
19:19of the trial.
19:22That is all that I
19:24had prepared
19:25for triple negative breast cancer
19:27and HER2 positive disease.
19:29But I'd love
19:31to turn the
19:33proverbial microphone over to Dan
19:35O'Neil,
19:36my colleague who is also
19:38a practicing breast medical oncologist
19:40to talk about
19:41hormone receptor positive breast cancer.
19:43And I will stop sharing
19:45and turn it over to
19:47you, doctor O'Neil.
19:57I'm told I'm muted. Okay.
20:00Thank you.
20:01Thank you to doctor Schallhorn
20:02for for doing the,
20:05the impressive work of of
20:06laying a lot of the
20:07groundwork about,
20:08you know, what metastatic breast
20:10cancer is and and the
20:12different types of metastatic breast
20:13cancer.
20:15I'm gonna be talking about
20:16hormone receptor positive breast cancer,
20:18and, you know, specifically hormone
20:19receptor positive HER2 negative breast
20:21cancer where we don't have
20:22overexpression of that HER2 protein.
20:25And just like Doctor. Shellhorn
20:26described,
20:28hormone receptor positive breast cancer
20:30is breast cancer that has
20:31expression of that estrogen receptor
20:33and or that progesterone receptor
20:36and is usually primarily driven
20:37by the estrogen and progesterone,
20:40hormones that, that that women
20:42are making, you you know,
20:44really over their entire lives,
20:46to some amount, and, and
20:48that you see circulating in
20:50the blood in a in
20:51a healthy woman. There have
20:53been a lot of updates
20:55in this in this space.
20:56I gave a similar talk
20:57about two years ago, and
20:58and when I went back
20:59to my slides, for for
21:00today's talk, I had to
21:01make a lot of updates.
21:02So so that's really good
21:04news.
21:04I'm gonna talk about about
21:06a lot of, specific drugs
21:07that we're we're using, and
21:09and how we sequence those.
21:11So, to start out thinking
21:13about the first line setting
21:14or the initial therapies,
21:17that a woman is likely
21:18to receive for, a new,
21:21or metastatic hormone receptor positive
21:24breast cancer,
21:25the standard there has remained
21:27the same for for some
21:28time
21:29now. The standard, therapy is
21:31a combination of a couple
21:32of different, types of drugs.
21:35The first type of drugs
21:36are are kind of,
21:38essential
21:39anti estrogen backbones,
21:41either aromatase inhibitors usually, which
21:43are an oral medication or,
21:45a injectable medication called fulvestrant.
21:49And those two medications have
21:51been around for a long,
21:51long time.
21:53But, within the last several
21:54years,
21:55a a newer type of
21:56medication, a CDK four six
21:58inhibitor has been incorporated into
22:00into the treatment,
22:01combination as well. So CDK
22:03four six inhibitors are drugs
22:05that,
22:07inhibit a pathway,
22:08that is part of the
22:10process
22:11that stands between,
22:13the estrogen receptor and the
22:15cell telling the cell to
22:16divide,
22:17in response to estrogen.
22:19So these CDK four six
22:20inhibitors interfere with that with
22:22that signaling, with that communication,
22:24and they help the,
22:26endocrine therapies, the anti estrogen
22:28therapies work for longer than
22:30they would all on their
22:31own.
22:32There are three different CDK
22:34four six inhibitors, that are
22:36available on the market. They're
22:37palbociclib
22:38or Ibrance, bemaciclib
22:39or Verzenio,
22:41and ribociclib
22:42or Kisqali.
22:44And in in the clinical
22:46trials looking at how long
22:48they improved,
22:49the time that a cancer
22:50was controlled in that first
22:52line setting,
22:53the the results were pretty
22:55similar.
22:56The average amount of time
22:56that a cancer could be
22:57controlled with these,
22:59these two drugs together
23:01was around two years or
23:02a little bit longer than
23:03two years, and that was
23:04that was consistent across all
23:06three drugs.
23:08In addition to that, there
23:09have been studies that look
23:10at how long overall life
23:12expectancy,
23:13is improved by by using
23:14these medications early on.
23:16And there there there are
23:18maybe some differences that have
23:19emerged,
23:20in in what we call
23:21real world trials or trials
23:23looking at patients, you know,
23:24actually out in the clinic
23:25receiving the drugs.
23:26There was suggestion that that
23:28all three drugs improved,
23:30life expectancy.
23:32In the in the kind
23:33of well controlled clinical trials,
23:36that led to the approval
23:37of these drugs, ribociclib
23:39was probably the best performing,
23:41increasing life expectancy by about
23:42it by about a year.
23:46So that's the first line
23:48setting. That's been stable. A
23:49lot of the the newer
23:50approaches and newer medications,
23:53really start to crop up
23:54in the, second line setting
23:56in in one situation and
23:57first line setting that I'll
23:58that I'll describe.
24:01When you're looking at,
24:03the next therapy, when when
24:04the cancer is no longer
24:05well, well controlled with those
24:07first drugs,
24:08something that's really important sort
24:10of thematically is to think
24:12about targetable
24:13mutations and how those play
24:14into, treatment selection.
24:17So, to sort of explain
24:18that,
24:20when,
24:21as the cancer is growing
24:23and becomes metastatic or, or
24:25continues to grow despite,
24:27despite medications,
24:29it's undergoing,
24:30sometimes undergoing genetic changes and
24:32developing,
24:33specific mutations.
24:35And in some cases, these
24:36mutations have drugs that, that
24:38are linked, drugs that, target
24:40those mutations effectively and can
24:41be particularly effective in those
24:43cancer
24:44types. But you need to
24:45have genetic testing to identify
24:46those mutations.
24:49Importantly,
24:50this sort of, the mutations
24:52I'm referring to refer to
24:53the mutations in the cancer
24:54cells. They're different from the
24:56mutations,
24:57that are in the healthy
24:58cells of, you know, a
24:59woman's body that might have
25:00been inherited by a family
25:01member.
25:02So this sort of genetic
25:04testing is different from the
25:05genetic testing that that many
25:06women undergo when they're first
25:07diagnosed, with with a breast
25:09cancer,
25:10be it metastatic
25:12or not metastatic.
25:14And it really includes testing
25:15the tumor tissue itself.
25:17As I mentioned, the mutations
25:18can guide treatment selection.
25:20And this testing can be
25:22performed in a few different
25:23ways. The most straightforward way
25:25probably is directly testing the
25:27tumor tissue itself. And that
25:29would require a biopsy of
25:30the tissue so that there
25:32was, you know, some tissue
25:33available for testing.
25:35Alternatively, sometimes you can do
25:37testing just on, using a
25:39simple blood draw.
25:40In that case,
25:42what's called circulating tumor DNA
25:43or DNA that's in the
25:45blood that's been shed by
25:46the cancer,
25:47can be isolated and tested
25:49for mutations.
25:51And
25:52an important thing to also
25:54keep in mind is that,
25:55as I sort of described
25:57a little bit already, these
25:58mutations do have, a tendency
26:00to develop and to change
26:01over time.
26:02So, each time,
26:04a new treatment is being
26:05considered,
26:06it can sometimes be helpful
26:08to, to repeat testing.
26:11So, I said there was
26:13a circumstance
26:14for initial therapy where,
26:16where identifying a targetable mutation
26:18can be helpful.
26:20And, I'm going to describe
26:21that. So,
26:23this is a relatively new
26:24approach.
26:26The specific circumstance I'm referring
26:28to are for breast cancers
26:29that meet two criteria.
26:32The first
26:33criteria
26:34is that the breast cancer
26:35recurred
26:37while a woman was taking
26:38what's called adjuvant endocrine therapy
26:40or kind of preventative,
26:42anti estrogen therapy,
26:44while she was in remission
26:45from
26:46her early stage breast cancer,
26:48or the breast cancer recurred,
26:50within a year of finishing
26:51adjuvant endocrine therapy. And then
26:53in addition to that, the,
26:55breast cancer needs to have
26:56a, a PIK3CA
26:57mutation.
27:00When those two criteria are
27:02met,
27:02there is a new,
27:04combination of three drugs that
27:06can sometimes be helpful for,
27:06first line treatment for that
27:06initial treatment. And those three
27:06drugs are fulvestrant,
27:08treatment for that initial treatment.
27:10And those three drugs are
27:11fulvestrant,
27:12the older,
27:14endocrine therapy, I described earlier.
27:17Palbociclib,
27:18one of the CDK4six
27:20inhibitors from that first slide.
27:22And then a new medication
27:23called
27:24Involisib,
27:25which is a PI3 kinase
27:28inhibitor pill. It's an oral
27:29drug that targets this PIK3CA
27:31mutation.
27:34The advantage of this triple
27:36combination,
27:37therapy is that it works
27:38to control cancer for longer
27:40than just fulvestrant and poblociclib
27:43by themselves.
27:44So, it can control cancer
27:46in about sixty percent of
27:47women as compared to, just
27:49about a quarter of women,
27:50with that set of circumstances
27:52I described,
27:54when you're using just those
27:55two drugs.
27:57In addition to,
27:59controlling cancer in more women,
28:00it also controls cancer for
28:02longer, typically
28:07it seems to work considerably
28:09better than the old,
28:11two pair of medications.
28:13A tricky thing about these
28:15combinations of multiple drugs is
28:17that as you add more
28:19drugs, you do often see
28:20more side effects and that
28:22can be a challenge.
28:24And that was indeed the
28:25case with these medications.
28:27So side effects
28:28that are common with these
28:30three drugs together
28:31include diarrhea, mouth sores, and
28:33sometimes high blood sugar levels.
28:35So, just as important as
28:37finding the right,
28:38cancer treatment,
28:40the other thing you have
28:41to do with your oncologist
28:42and that we spend a
28:44lot of time doing is
28:45working together on trying to
28:46control side effects.
28:49Okay. So, moving on to
28:50the to the,
28:51second treatment.
28:55The,
28:57or moving on to the
28:58second line therapy, excuse me.
29:01For a long time after,
29:03that,
29:04aromatase inhibitor,
29:06treatment stops working in the
29:07in the first line setting,
29:09the standard approach was to
29:10move on to this, fulvestrant
29:11medication.
29:12Fulvestrant is an intramuscular injection
29:15that you have to receive
29:16every four weeks, which is,
29:19is not necessarily
29:20a pleasant treatment to be
29:21receiving.
29:23And,
29:24on its own, its response
29:26time or the response,
29:28time of the cancer is
29:29not always as long as
29:31we would hope.
29:32And so, there have been
29:33a number of,
29:35different options,
29:36that have been developed recently
29:37to try and improve on
29:39those outcomes,
29:40and to improve on the
29:41just the experience of receiving
29:43the drug.
29:45So, the first options I'll
29:46go through are drugs that
29:48target the ESR1 mutation.
29:51The first of those is
29:52a medication called
29:54Elisestrin. Elisestrin has been on
29:55the market for about two
29:56years now.
29:58It's a pill. It's not
29:59an injection. It's a pill
30:00that has the same mechanism
30:02as fulvestrin. It's what was
30:03called a selective estrogen receptor
30:05degrader.
30:08And, compared to fulvestrant in
30:10women who have an ESR1
30:11mutation,
30:13it controls cancer longer. So,
30:15it works better than fulvestrant
30:16in addition to being an
30:17oral medication for women with
30:19an ESR1 mutation.
30:21It seems to work best
30:22and really that extra benefit
30:24is mostly seen in women
30:25who have, were able,
30:27whose cancer was controlled for
30:28at least twelve months, on
30:30their first line anti estrogen
30:32therapy.
30:33So those are women who,
30:34you know, it seems like
30:35their cancer is still sensitive
30:37to anti estrogen therapies.
30:39And it can have some
30:41side effects, but usually they're
30:42not particularly,
30:43difficult. It can have a
30:45variety of GI side effects.
30:46And can have some of
30:47the same sort of anti
30:48estrogen menopause type side effects
30:50that you see with other
30:51anti estrogen medications.
30:54There is a,
30:56practically brand new option,
30:59for women with ESR one
31:01mutations, that is is similar
31:02in some ways to elocestrant.
31:04It's called, illumin illuminestrant.
31:07Also a lot of vowels
31:08in that one.
31:09It is also an oral
31:11SIRD, just like the elocestrant.
31:14And, just like elacestrant,
31:17it controls cancer for longer
31:19than fulvestrant amongst women with
31:20ESRO mutations.
31:22What makes it a little
31:23bit different is that in
31:25the
31:26trial that led to its
31:27approval,
31:28there was a a third
31:29group of women who received,
31:32the, in luminescent in combination
31:34with the bemiciclib.
31:35And in that group of
31:36women,
31:37the amount of time the
31:39cancer
31:39even longer than with either
31:41of the the single agent
31:43drugs.
31:44That use has not been
31:45fully reviewed and approved by
31:47the FDA yet, but it's
31:48something that that might be,
31:51might have potential in the
31:52future.
31:53And as I mentioned, this
31:54drug was just approved by
31:55the FDA towards the end
31:56of September. So it's it's,
31:57just kind of coming,
31:59it's just becoming widely available.
32:05The,
32:09in addition to those oral
32:10sird,
32:11there's a there are some
32:12other types of medications, some
32:14other some medications with alternative
32:16mechanisms of action,
32:18for women with the ESR
32:19one mutation.
32:20One example of that is
32:21a medication called veptigestrin.
32:24It is a pill with
32:25a, with a slightly different,
32:27sort of,
32:28mechanism for
32:30destroying or degrading the estrogen
32:32receptor.
32:33It also increases time on,
32:36of control
32:37of the cancer and when
32:38with ESR1 mutations.
32:40This has been studied and,
32:42these results have been, shared
32:44with, the scientific community, but
32:46it hasn't been approved by
32:47the FDA yet. It's under
32:48review. So, potentially sometime in
32:50the next year, it'll become
32:51available as well.
32:54So, moving on from ESR1,
32:56what about some of the
32:57other, mutations that we look
32:58for?
32:59There are a group of
33:01mutations that are part of
33:02what we call the AKT
33:03pathway.
33:04The AKT pathway is an
33:05alternative,
33:06pathway that, leads to resistance,
33:09sometimes to,
33:11standard anti estrogen therapies.
33:13And there are a number
33:14of genes that are involved
33:15in the pathway, but three
33:16in particular that can be
33:17targeted are the, PIK3CA mutation
33:20or gene, the AKT1 gene
33:22and the P10 gene.
33:24So, when mutations in those
33:25genes are seen,
33:26a medication that can be
33:27useful in combination with, fulvestrant
33:30is called capivacertib
33:32or, TrueCap is the, the
33:33brand name there.
33:36It is,
33:37targeting the similar part of
33:39the, of cell communication as
33:41this older medication,
33:43called pick Ray that many
33:44of you may have heard
33:45of.
33:45Pick Ray is,
33:47is an older oral drug,
33:49that has a lot of
33:50side effects,
33:51and was difficult to use,
33:53I think, for many women
33:54because of the degree of
33:56side effects,
33:57that came along with it.
33:59Cabivastatinib
34:00is approved for all three
34:02of these mutations or for
34:03use in women whose cancer
34:05has all three of these
34:05mutations or any of them.
34:06They don't have all three
34:07at once, just any one
34:08of them.
34:10And it seems to be
34:11useful in women who have
34:12spent,
34:13even less than twelve months
34:15on, their first line endocrine
34:16therapy.
34:18It can cause some side
34:18effects, some GI side effects,
34:20and some rash. It doesn't
34:21cause as much, high blood
34:23sugar as the PICRae, but
34:24it does still require blood
34:26sugar monitoring.
34:29And
34:30sometimes, I mean, really not
34:32it's not rare that a
34:33woman,
34:34when she progresses on first
34:36line therapy might not have
34:37any target mutations.
34:39And so, in that case,
34:41we ask questions like, should
34:42we keep going with our
34:43CDK4six
34:44inhibitor when we change the
34:46underlying anti estrogen medication?
34:48There have been a couple
34:49of different trials, or more
34:51than two, but I'll talk
34:52about two,
34:54that look at this question.
34:56The first of those was
34:57called the PACE trial.
34:59And the PACE trial,
35:01looked at or had two
35:03groups of women in it.
35:04Women who progressed on, their
35:06first line treatment with their
35:07CDK foursix inhibitor. And they
35:09received either full vestrant, the
35:10standard,
35:11approach by itself or full
35:13vestrant with pelbociclib.
35:15Now, most of the women
35:16in that trial had gotten
35:17pelbociclib
35:18as their first CDK4six
35:19inhibitor also. So, this was
35:20really a continuation of the
35:22same,
35:23the same drug for these
35:24women, generally speaking.
35:27And
35:28when using this approach, unfortunately,
35:30there wasn't really any sort
35:32of improvement in how, how
35:33well fobesterone performed.
35:35The cancer progressed,
35:36at the same kind of
35:37pace in both
35:39groups of women.
35:41But what if we switch?
35:42What if we change the
35:43CDK4six inhibitor to one of
35:44the other two?
35:46So the Maintain trial gave
35:47us some information about that
35:49approach.
35:49It compared,
35:51in second line therapy in
35:53women who had gotten the
35:53CDK4six
35:55inhibitor. It compared new endocrine
35:57therapy alone or new anti
35:59estrogen therapy plus ribo cyclob.
36:01And for about eighty eight
36:02percent of patients in that,
36:04study,
36:05that ribo cyclob was a
36:06change. It was different CDK4six
36:08inhibitor than what they previously
36:10received.
36:11In that case, the fulvestrant,
36:13with ribociclib,
36:14did improve,
36:15time on therapy.
36:17So, this doesn't, you know,
36:18kind of tell us about
36:19every situation with, switching CDK4six
36:22inhibitors, but it does give
36:23us some reason to believe
36:24that, that they might be
36:25useful, if there are no
36:26targetable mutations present.
36:30For the for the sake
36:31of time and for the
36:32sake of allowing questions,
36:34I'm, I'm gonna, not really
36:36talk, specifically about medication, you
36:38know, non anti estrogen medications
36:40for, hormone receptor positive breast
36:42cancer. But, but I will
36:43say, also just a little
36:45bit about, trial options that
36:46are available at the, at
36:47the Yale Cancer
36:49Center. The, the trials that
36:50we have tend to turn
36:51over over time. So, specific
36:53trials, you know, kind of
36:55come and go and we
36:56open new ones and we
36:57close.
36:58But,
36:59to think about some of
37:00the common questions,
37:02or the themes in the
37:03questions that,
37:05that are really at top
37:06of mind right now.
37:09So, one, you know, kind
37:10of common theme of the
37:11questions being asked
37:13by the, by trials for
37:14hormone receptor positive breast cancer
37:15is with all of these
37:17new drugs, are there ways
37:18that we can combine them,
37:19into,
37:21you know,
37:22larger combinations
37:23and get better results, for
37:26cancer patients?
37:27So, for instance, we have
37:28a trial right now that
37:29combines cabivacertib
37:31that, AKT pathway inhibitor, the
37:33true cap medication
37:34with a CDK4six
37:36inhibitor
37:36and with fulvestrant. And this
37:38is a trial that's looking
37:39at women who have the
37:40targeted mutations and women who
37:41might not have the targeted
37:43mutations.
37:44Another type of question we're
37:45asking is, are there,
37:47novel ways that we can,
37:49administer these medications that,
37:51that reduces side effects, reduces
37:53toxicity.
37:54So, for instance, we have
37:55a trial, for older women,
37:57women over the age of
37:58sixty five looking at whether
38:00or not we can give
38:01the CDK four six inhibitors,
38:03in the first line setting,
38:05starting at a low dose
38:06and going up rather than
38:07starting at the highest dose
38:08that we offer and going
38:09down if they if if
38:11the dose is too high
38:12for them.
38:13And then, of course, we
38:14we all there's always new
38:16drugs.
38:17And so, we have novel
38:18drug trials, too.
38:20An example is,
38:21this drug, which doesn't even
38:23have a kind of scientific
38:24name yet but still sort
38:25of an industry shorthand.
38:27Relay two thousand six hundred
38:28and eight, which is a
38:30selective
38:31PI3 kinase inhibitor.
38:33And a selective,
38:35adjective sort of refers to
38:36its potential to maybe have
38:38fewer off target effects. And
38:39those off target effects are
38:41what cause toxicity.
38:44Toxicity than than some of
38:46the existing drugs in this
38:47class.
38:49So, I think I'll I'll
38:50stop there,
38:51and,
38:52we could we could open
38:53it up for questions.
38:58And maybe I'll I'll stop
38:59sharing too. You don't have
39:00to look at a black
39:00screen.
39:02Yeah. Dan,
39:03the question that,
39:05on Hartoulo disease and kind
39:07of,
39:08you can see it in
39:10the q and a. It
39:11may come up as answered,
39:13but
39:13I think it's the question
39:15that
39:16is a wonderful one in
39:17terms
39:18of what to do in
39:19the setting of HER2 low
39:21hormone receptor positive breast cancer
39:24and how you're envisioning,
39:26kind of
39:27the sequencing of HER2 ADCs
39:30in this setting,
39:32kind of earlier versus later.
39:34So if you could share
39:35your thoughts on that.
39:36Yeah. Yeah. Absolutely.
39:38You know, this is a
39:39question that actually applies to
39:41both,
39:42the types of breast cancer
39:43that, doctor Shalhoren and I
39:45spoke about. So HER2 low
39:47is sort of a newer
39:48idea,
39:49in in the breast cancer
39:50space or almost like a
39:51new classification
39:55three
39:56buckets that that we've been
39:57talking about is is sort
39:58of how we classically thought
40:00about breast cancer subtypes.
40:01But I I think in
40:02doctor Schallhorn's slide describing what
40:04HER2 HER2 is,
40:06you could see on that
40:07normal,
40:08cell that there was still
40:09HER2 protein. Like, it's when
40:11we talk about HER2 negative
40:13cancers, that doesn't mean there's
40:14no HER2 protein.
40:15So so HER2 low breast
40:17cancers refer to HER2 or
40:19breast cancers that have some
40:20HER2 protein, but not necessarily
40:22this over expressed amount. This,
40:24like, extra HER2 protein that,
40:26that,
40:27has typically made those cancers,
40:29more sensitive to the anti
40:31HER2 drugs.
40:33Why that's an important distinction
40:35to make now, why it's
40:36important to identify cancers that
40:37have some but not too
40:39much HER2 protein
40:40is because one drug in
40:42particular so far and then
40:43surely more in the future.
40:44One one particular drug, the,
40:47trastuzumab, drexatecan,
40:48the HER2 drug that,
40:50that Doctor. Shellhorn talked
40:52about, is actually effective not
40:53only in classically HER2 positive,
40:56breast cancer, but is also
40:58effective
40:58in HER2
41:00low breast cancer.
41:01So, if you're hormone receptor
41:03positive, HER2 negative, but HER2
41:04low, then HER2 can be
41:06it can be very effective.
41:08If you're a triple negative
41:09but HER2 low,
41:10that that, and HER2 can
41:12be very effective.
41:13And so we've been we've
41:14been using that drug for
41:16several years now for those
41:17types of breast cancers as
41:18well.
41:19In in terms of sequencing,
41:22the the
41:23the,
41:26standard, I would say, is
41:28still
41:29for hormone receptor positive breast
41:30cancer is is to really
41:32make the most of the
41:33anti estrogen therapies.
41:35Those cancers are still most
41:36sensitive to anti estrogen approaches,
41:38like the anti estrogen medicines
41:40work best and and longest,
41:41for hormone receptor positive breast
41:43cancers,
41:44early on.
41:46They tend to have fewer
41:47side effects.
41:49Well,
41:51experiences can be mixed, actually.
41:52I don't want to say
41:53that HER2 has
41:54a lot of side effects
41:55for everyone, or that the
41:57antihistamine medications don't have side
41:59effects. It can be significant.
42:01But oftentimes they have fewer
42:03side effects,
42:04than,
42:05the inher tube medication. So,
42:07we still try to use
42:08as many, antiastrogen medications as
42:10possible,
42:12before changing to infusional
42:15chemotherapy based medications. Medications.
42:17And then
42:18there is some, you know,
42:20some recent conversation about whether
42:22HER2 should be the very
42:23first drug that we use
42:24after anti estrogen medication or
42:26if,
42:27if chemotherapies
42:29can,
42:30still, you know, if a
42:32chemotherapy before moving to an
42:33HER2 is appropriate.
42:35And that conversation is really
42:37based on balancing
42:39length of response versus,
42:41versus,
42:42side effects
42:43and whether or not a
42:45drug that might control the
42:46cancer longer but have more
42:47side effects,
42:48whether or not you could
42:49kind of get the same
42:50effect by by turning to
42:52that drug a little bit
42:53later.
42:55So,
42:55it's, it's an exciting space.
42:57I mean and and and
42:58it's a space where I
42:59think there there will be
43:00a lot of new medications
43:01over the over over the
43:02coming years.
43:04And I think for the
43:04listeners, this is your opportunity
43:06when these junctures are occurring
43:08in your care
43:10to be asking your oncologist,
43:12what are my options? What
43:13are my alternatives? And,
43:15I think,
43:16what we all aim for
43:18is to
43:19summarize
43:21currently, as as my colleague
43:22just mentioned, there are so
43:24many options for each line
43:25of therapy in breast cancer.
43:27So a lot will come
43:28down to patients actively deciding
43:31with their oncologist
43:33based on preferences of schedule,
43:35side effects, and so many
43:36other considerations. So don't be
43:38afraid
43:39to be bringing up these
43:41questions.
43:41We we would love to
43:42have these conversations.
43:45There is a there was
43:45a question in the chat
43:47that's also an excellent one
43:48in terms of
43:50when we test,
43:51for these different, targetable pathways.
43:54So doctor Shellhorn will answer
43:55that live. Yeah. No. It
43:57it's a it's a great
43:58question, and doctor O'Neil
44:00talked a lot about targetable
44:02mutations.
44:04It it's applicable for any
44:07type of breast cancer, at
44:08least to some degree. It's
44:09particularly relevant for cancers that
44:11are driven by hormones. So
44:12the hormone receptor positive breast
44:14cancers.
44:16Doctor O'Neil mentioned
44:18specifically
44:18ESR one,
44:21looking at anything in the
44:22AKT pathway. So AKT p
44:24ten PI three kinase,
44:26PIK three CA,
44:27as well as a few
44:28other mutations that have
44:31that are that are considered
44:32druggable. Meaning, we have drugs
44:35that that
44:36focus on those molecular engine
44:39genomic abnormalities
44:40and and help kind of
44:42turn off the switches that
44:44might be driving the cancer.
44:46And so
44:48there's no right answer or
44:50wrong answer to how often
44:52to be testing.
44:54And I think kind of
44:55a a a corollary to
44:57this is how to test
44:59because there are a couple
44:59of ways that you can
45:00test for genomic abnormalities. You
45:02can test the cancer itself
45:04on a biopsy specimen.
45:06So you if you have
45:07a cancer that's got a
45:08deposit in the liver, for
45:09example,
45:10you could get a liver
45:12biopsy to take a sample
45:13of that particular tissue and
45:14then send it to the
45:15to the lab to look
45:16at under the microscope where
45:18we would test for estrogen
45:19receptor, progesterone receptor, HER2, and
45:21we could also then send
45:22it for all of these
45:24molecular tests to look for
45:25any sort of genomic abnormality.
45:30But you can also
45:31do what we call a
45:33liquid biopsy, which is a
45:35blood test,
45:36looking at
45:38DNA from the cancer that
45:40might be circulating in the
45:41blood and getting that same
45:42information in a much less
45:44invasive way. So it doesn't
45:46require a biopsy or a
45:47needle. It just requires a
45:48blood draw.
45:50And so with the advent
45:52of these liquid biopsies,
45:56the the opportunity
45:58is is much less risky
46:01and much easier to do
46:03at any point where it
46:04could theoretically change management.
46:06And so I think most
46:08of us are testing pretty
46:10early on,
46:12maybe not immediately
46:14after a diagnosis of metastatic
46:16breast cancer. But, again, it
46:17might depend on on
46:19what what a patient's,
46:21what a patient's story is,
46:22what their history is, had
46:23they gotten prior treatment, and
46:25if so, how long ago,
46:26and what medicines were they
46:27on?
46:29So you might test as
46:30early as right then and
46:31there at the first
46:32the first sign of metastatic
46:34disease.
46:36But I think for certain,
46:38after progression on first line
46:40therapy for hormone receptor positive
46:42breast cancer because that's when
46:44these molecular targets really become,
46:48become relevant
46:50after progression on on
46:52the first line, usually an
46:54aromatase inhibitor and a CDK
46:55four six inhibitor as doctor
46:57O'Neil described.
47:00But then things can change
47:02over time and things can
47:03develop. So for example, that
47:05ESR one mutation
47:07ESR one mutation
47:09isn't usually very common right
47:11at the time of a
47:12metastatic diagnosis unless someone had
47:14been on,
47:16previous therapies. It but it
47:17can develop,
47:19in even up to forty,
47:20fifty percent of patients who
47:22have been on aromatase inhibitors
47:24over time. So we would
47:26check
47:27periodically
47:28at the time
47:30that there's a a sense
47:31of the cancer starting to
47:32progress,
47:34check for for circulating tumor
47:36DNA, check for mutations
47:38with the idea,
47:40that something targetable
47:41if something targetable were found,
47:43we could then
47:45target it.
47:47And the other time to
47:48consider molecular testing
47:50is
47:51when considering clinical trials because
47:54there are new drugs becoming
47:55available for particular mutations,
47:58certain earlier phase clinical trials
48:01that are,
48:03applicable to patients with certain
48:09FDA approved
48:10targetable,
48:14druggable targets at this point.
48:17So
48:18lots of opportunities, and it's
48:20getting easier and easier to
48:22do.
48:23Kim, I hope that answers
48:24your question.
48:27Yes. And there was also
48:29an additional question about is
48:31ESR one testing ever done
48:32in early stage breast cancer.
48:34And I would say,
48:36one, two points there. These
48:37are
48:38acquired alterations that
48:41occur under selective pressure
48:44of
48:44more longer exposure to anti
48:47estrogen therapy. So you're unlikely
48:49you're gonna have a low
48:50chance of finding it early
48:51on in early stage breast
48:52cancer.
48:53However, there are studies investigating
48:56adjuvant SIRDS in high risk
48:58early stage breast cancer.
49:00So as often happens, if
49:01something is approved and shown
49:03to be effective in metastatic
49:04breast cancer, we do start
49:06testing it in early stage
49:07breast cancer.
49:09There are couple of questions
49:11in the chat that are
49:13are complex, so we might
49:14need to kind of tag
49:15team it.
49:17So,
49:21so let's,
49:23let's take the question from
49:24doctor Ward,
49:27on,
49:28will doctor Ward is one
49:29of our,
49:31amazing breast surgeons,
49:32within Yale network. So,
49:36so in the setting of
49:37oligometastatic
49:38disease
49:38and a primary breast tumor,
49:40who wants to tackle this?
49:41What is the current thinking
49:43on breast surgery?
49:45Doctor Ward wants to be
49:46a little provocative
49:48at our Smilo shares,
49:50Smilo share session.
49:52So the question is specifically
49:54asking if somebody has a
49:56primary breast cancer that's in
49:59the breast and they're diagnosed
50:00with that breast cancer, but
50:01they are found
50:03to
50:04have one or just a
50:06few
50:07spots
50:08on on a staging scan.
50:09So on a CAT scan
50:11or a PET scan, they're
50:12found to have another spot
50:14somewhere else in their body.
50:16Is there a role
50:18for doing surgery
50:20to the breast?
50:22Because at that point, kind
50:23of the traditional way that
50:25we think about this is
50:26that once the cancer has
50:28spread
50:29outside of the breast,
50:31it's no longer considered curable.
50:33And so
50:35curative approaches,
50:36including breast surgery,
50:39are generally
50:40not not considered.
50:42I'd say this is an
50:43area of a lot of
50:45research,
50:46especially
50:48in
50:48HER two positive breast cancer
50:50and in triple negative breast
50:52cancer
50:53because
50:54sometimes
50:55those types of cancers are
50:57very, very responsive
50:58to chemotherapy.
51:02The data that we have
51:04to date
51:05does not show a benefit
51:06to
51:08to,
51:09primary breast surgery
51:11in the setting
51:12of metastatic disease. But these
51:14studies aren't perfect, and so
51:16there are some ongoing
51:17studies being done to look
51:19at particular subsets of patients
51:21to see if there are
51:22benefits. And I,
51:23I will say that for
51:25all of the medical oncologists
51:27in our practice, we all
51:28have patients
51:30who have had,
51:32they may have had metastatic
51:33disease, and they may have
51:35had surgery, and they may
51:36have had radiation,
51:38very strong radiation with the
51:40goal of of trying to,
51:43sterilize
51:44metastatic
51:45deposits.
51:46And they do
51:48really, really well
51:49for a really long time
51:51and don't have evidence of
51:52further cancer. I know I
51:54know that there's at least
51:56one of them on this
51:58call right now who's who's
52:00listening in.
52:02People so we can't fully
52:03explain why that happens, but
52:05what what our goal in
52:06terms of the research going
52:07forward is is to figure
52:08out
52:10who are those patients
52:12that can benefit from a
52:13more,
52:15aggressive approach and continue to
52:17do well in the long
52:18run rather than go through
52:20very big surgeries,
52:22very aggressive treatments, and not
52:24benefit in the long run.
52:28Yeah. I think I think
52:29comes back to
52:31shared decision making and really
52:33looking at each individual patient.
52:35Bringing it back to tumor
52:36board, which is one of
52:37the questions that is densely
52:38packed,
52:40in one of our chat
52:41questions, which which is, does
52:42a single oncologist determine the
52:44treatment plan, or is it
52:45a collective decision?
52:46I can say that,
52:48if it's if something is
52:50very straightforward,
52:51the decision is made between
52:52the oncologist and the patient
52:54in the room right then
52:55and then. But any nuances,
52:57any complexities,
52:58I do wanna assure all
53:00of you that we're talking
53:01all among each other.
53:03We're bringing it back to
53:04tumor board,
53:06and also just encouraging you
53:08that if if you're unsure
53:09or want additional opinions,
53:11it's never wrong to explore
53:13second opinions. It's actually your
53:15right as a patient.
53:18Additional
53:19questions about
53:21just
53:23we kind of answered the
53:24question if it's a new
53:25cancer, are all markers tested
53:27again? And, yes, we we
53:28definitely wanna understand
53:30the biology of a new
53:31recurrence.
53:35And I think maybe, Dan,
53:37take that first part of
53:38the question about late recurrences
53:40and hormone receptor positive breast
53:42cancer
53:42and how it can be
53:43different with different subtypes of
53:45cancer.
53:46Yeah. Yeah. That that is
53:47a that's a great question.
53:49So just like there are
53:51different subtypes of breast cancer,
53:52the the behavior of different
53:54cancers in terms of likelihood
53:55of recurrence,
53:56can be quite different,
53:58and the timing can be
53:59different.
54:00So, the the kind of
54:02rule of thumb is that
54:03the more aggressive,
54:04more,
54:05faster growing
54:07cancers, if they're going to
54:08recur, they're more likely
54:10to recur,
54:12in a shorter timeframe
54:14or at very least the
54:15highest risk periods for recurrence
54:17are earlier on.
54:19So for HER2 positive breast
54:20cancer, triple negative breast cancer,
54:23you sort of have the
54:24highest risk of recurrence over
54:25the first three and then
54:27over the first five years.
54:28And as you get further
54:29from that period of time,
54:31the likelihood of recurrence
54:32gets lower and lower.
54:34HER2 positive breast cancer,
54:37has,
54:39a lower
54:41or hormone receptor positive breast
54:42cancer has a,
54:44a lower likelihood
54:45of coming back
54:47period in most cases when
54:48sort of size and other
54:50things are all considered.
54:52So,
54:53so, for early stage breast
54:54cancer, hormones that are positive
54:56breast cancers are less aggressive,
54:57less likely to come back,
54:59generally speaking.
55:01But that, that because they're
55:03slower growing, sometimes the risk
55:05of recurrence,
55:06over time,
55:07doesn't always drop off to
55:10zero.
55:11You can have
55:12a low risk of recurrence
55:14that can continue out for,
55:15for years sometimes.
55:18I think at, you know,
55:19twenty plus years,
55:20the likelihood of the cancer
55:22coming back is probably quite,
55:24quite low.
55:25You know, just the proof
55:26is in the pudding over
55:27time that it hasn't recurred.
55:31But,
55:32but there are situations, I
55:33think, that we've all seen
55:34where sometimes there can be
55:36late recurrence. And it's important,
55:38I think, for,
55:40for women to just be
55:42mindful of their bodies and
55:44what's going on, with their
55:45bodies and, you know, not
55:47be,
55:49shy about letting
55:52their doctors, be it an
55:53oncologist still or a primary
55:55care doctor, whomever they're
55:57getting their care from,
55:58know if if something feels
56:00unusual.
56:03Is it if that cancer
56:05comes back, is it always
56:06metastatic?
56:07Not necessarily. There are two
56:08types of recurrence. There's local
56:09recurrence and distant recurrence. And
56:09distant recurrence sort of refers
56:09to that that metastatic,
56:12And distant recurrence sort of
56:14refers to that, that metastatic,
56:14disease. The disease that's in
56:16organs outside of the breast
56:17or outside of the nearby
56:18lymph nodes. Local recurrence can
56:20be, the cancer coming back
56:22right in the breast either,
56:23you know, usually in the
56:24vicinity of where it was
56:25originally
56:26or sometimes in the lymph
56:27nodes that,
56:29that are surrounding the breast
56:31that is often the first
56:32kind of place, cancer begins
56:34to to travel to.
56:37So either of those situations
56:39are are possible. I mean,
56:40that's also the reason why,
56:41you know, it's important to
56:42keep getting mammograms.
56:43The the other reason why
56:44it's important to keep getting
56:45mammograms is because
56:48as long as you're,
56:50as long as you're a
56:51woman alive with breast tissue,
56:53there is some risk of
56:54developing a new breast cancer.
56:56And, and and just because
56:58you've had a breast cancer
56:59in the past doesn't mean
56:59that you can never have
57:00a breast cancer again. So
57:02continuing to get mammograms,
57:03so that you pick up
57:05on any new breast cancers
57:06when they're still early is
57:07is important.
57:08New breast cancers can can
57:10certainly show up.
57:12I could I could I
57:13could
57:14talk a little bit about
57:15I think we have a
57:16couple of Yeah. And then
57:17just to clarify for the
57:18audience that, but in the
57:19setting of active metastatic disease,
57:21you're getting thorough scans frequently.
57:24So in that setting, we're
57:26when we do not recommend
57:27additional routine mammography, that has
57:29not been shown to be
57:30helpful.
57:33We're almost at time. Just
57:34one remaining thing is that
57:36in metastatic disease, unlike early
57:38stage breast cancer, the treatments
57:40continue
57:41as long as they're helping
57:42you and as long as
57:43they're controlling the disease process.
57:46But there are situations where
57:47there may be,
57:49you know, we we've had
57:51times where disease has been
57:52completely stable for some time.
57:54So, again, comes back to
57:55shared decision making
57:56about whether,
57:58a certain type of,
58:00de escalation or therapy break
58:02can be considered. But, generally,
58:04things are left open ended
58:05as long as they're helping
58:06you and, keeping the disease
58:09at bay.
58:10Lots of different chemo cycles
58:12and targeted schedules, so we
58:13won't get into that. Definitely
58:15ask your oncology team about
58:17that. But you've all been
58:19such an amazing audience with
58:20really great questions, and I
58:23wanna thank again our speakers
58:25today, doctors,
58:27Shellhorn and doctors O'Neil.
58:29And thank you so much
58:30for joining us. Thank you,
58:32Mary Ellen, for joining.
58:34Thank you. Bye bye.
58:36Bye bye. Okay, man.