Smilow Shares: Breast Cancer at Waterford/Westerly

October 29, 2020

Information

Smilow Shares: Breast Cancer Awareness, presented by the Smilow Cancer Hospital Care Center in Waterford and Westerly

Mehra Golshan, MD, MBA - Professor of Surgery (Oncology) and Interim Director of the Breast Center at Smilow Cancer Hospital

Anca Bulgaru, MD - Assistant Professor of Medicine (Medical Oncology)

Robert Legare, MD - Associate Professor of Clinical Medicine (Medical Oncology) and Medical Director of the Smilow Cancer Hospital Care Centers in Waterford and Westerly

Meena Moran, MD - Professor of Therapeutic Radiology, Director of Breast Radiotherapy

ID5827

To CiteDCA Citation Guide

00:00Good evening everyone.
00:01My name is Mara, Gulshan Anama,
00:04breast cancer surgeon, here at Yale.
00:08The clinical director of the breast program,
00:10Ann, really excited to be here
00:13this evening for the Smilow shares
00:15breast Cancer Awareness Month.
00:18Where we have a three preeminent
00:20authorities and breast cancer,
00:22this evening doctor,
00:24Uncle Garo we're going to have Doctor
00:27Bob Legare and Doctor Mina Moran
00:29talk about advances in oncology,
00:32radiation therapy,
00:33and really just a state of the art and
00:36treatment in breast cancer were going
00:39to have three separate presentations.
00:42And then at the end there will be a
00:46question and answer period where.
00:49And even in advance of the end,
00:51if you want,
00:52please put in any questions into the
00:55chat box or on the Q and a box that
00:57sat at the bottom of your screen.
01:00We've held two of these forums
01:02for Yale for the New Haven and
01:04also for the Fairfield,
01:05Bridgeport,
01:06but it's been a really well received
01:08and this is going to be the
01:10highlight of the month for breast
01:12cancer awareness and Smilow shares.
01:14So with no further ado,
01:16we're going to start with Doctor
01:18Bob Legare who's going to talk.
01:20About some advances in breast
01:22medical oncology.
01:22Then Doctor Mina Maranan radiation
01:24and certainly not last and not
01:27least but will have Doctor Bogart
01:29talk a little bit more about some
01:32of the advances in oncology and
01:34then look forward to some really
01:36great questions from the audience.
01:38Thank you Doctor Laghari at
01:40the floor is yours.
01:42Thank you, I appreciate that and I'm
01:45very happy to be with everyone tonight.
01:48And I'm going to try to share my screen.
01:51Just let me know if you can see things.
01:55Properly, can you see my screen?
01:59OK, so good evening and very excited
02:02to share some thoughts with you.
02:05Um, you know regarding breast cancer,
02:07maybe where we're heading where we
02:09hope to head, and some of the advances
02:11that we've seen come forward this year.
02:14We know that breast cancer remains.
02:16Significant, it's the most common
02:18malignancy that's not a non
02:21Melanoma skin cancer in women,
02:23estimated to be about 276
02:25thousand new cases this year.
02:28So we know that this is a very significant.
02:33Issue for our women across the
02:35world and certainly United States
02:37and something where research,
02:39really, I think is moving forward
02:41in a very hopeful way you can see
02:44on that top sort of purple pink
02:46part of this graph that you know,
02:49breast cancer probably had a
02:50little bit of a dip in the early
02:532000s in terms of incidence rates,
02:55and that was perhaps based on
02:57folks moving a little bit away
02:59from home replacement therapy.
03:01And then after that we can
03:03see maybe a slow rise maybe.
03:05.3% per year increase in risk of
03:08breast cancer that we've seen.
03:10Subsequent to that,
03:12perhaps over the last decade.
03:14And I would say it, you know,
03:16as a combination of.
03:18Early detection with mammogram having
03:20shown to decrease mortality from
03:23breast cancer through screening.
03:25And also with advances in
03:27treatment we've seen.
03:29Thankfully,
03:29especially over the last decade,
03:31you know significant decrease
03:33in breast cancer mortality,
03:35so we've seen perhaps a 40% decrease
03:38in breast cancer mortality since 1989,
03:41after seeing essentially
03:42fairly flat lines before then,
03:44you can see that again in that
03:47purple pink curve there on the graph.
03:51So we are making progress.
03:53We can never be complacent.
03:56Now we have a long way to go,
03:58but there's this room for hope.
04:01When we look at 5 year survival rates,
04:04this can also be reflected going
04:07from the 70s to the 80s to you
04:10know the last decade and we're
04:12seeing five year survival rates
04:15increased from 75 to 84 to 91%.
04:20I was going to focus a bit on ER
04:22positive her two negative breast
04:24cancer and later tonight you'll hear
04:27some advances and her two positive
04:29breast cancer from Doctor Ogarro.
04:31We know that.
04:32Early breast cancer accounts for
04:35perhaps 90% of breast cancers
04:36diagnosed in women and 70% of those
04:39are hormone hormone receptor positive.
04:41In her two negative,
04:42we know that thankfully most women
04:44won't experience a recurrence,
04:46but some women will be at higher
04:48risk and those would be folks who
04:50have had high risk features and
04:52they can experience recurrence.
04:54Sometimes within the first few years
04:56and one of the questions that we ask,
04:59is you know why is this happening
05:02on our current therapeutics,
05:03and one question that we look at.
05:06Is is the question of.
05:09Endocrine refractory nessuno.
05:10When one is getting treated, say,
05:12with endocrine therapy of some type,
05:14what's permissive for that cell if
05:16it exists within the body to then
05:19grow back and manifest as stage four
05:21cancer after one is presented with
05:24early stage cancer, and there is some
05:26interesting trials that that we're
05:28looking at this question a bit at our
05:31American Society of clinical oncology
05:33meetings earlier this year, so it's
05:35hoping to highlight just a few of those.
05:39Trials and then to just take a look at some
05:42of the clinical research that's happening
05:44at Yale right now to share with you.
05:47This was a cartoon of sort of cell cycle
05:51kinetics if you will and how a protein calls.
05:56You know cyclin D works and how it affects
05:59cell cycle kinetics and just looking
06:02at that that that green circle RBRB,
06:06which is the retinoblastoma gene,
06:08is very important in controlling
06:10whether a cell replicates,
06:12you know, makes a copy of itself.
06:16Cell Grove cell replication.
06:18We know that dysregulated cell growth and
06:21replication is the hallmark of cancer.
06:24Now we know that mutations within cancer
06:27cells are what ultimately causes that
06:30this data in the stage 4 setting that
06:34adding a cyclin dependent kinase inhibitor
06:37to endocrine therapy hormone therapy,
06:40like anastrozole or an aromat
06:43ACE inhibitor or a surd like.
06:46A full best friend can almost double
06:49the progression free survival in the
06:51stage for setting, and like many,
06:54many aspects of how we study cancer.
06:56If something looks very hopeful
06:58in the stage for setting,
07:00we try to move it back to the early brand.
07:05Cancer setting and say hey,
07:07can we do better so documenting
07:09benefit in the advanced setting?
07:12In trying to block that.
07:15Movement from the G1 phase
07:18of the cell cycle to the.
07:23DNA replication phase.
07:26We've tried to look at these agents
07:29in the early stage of breast cancer,
07:32so this is a trial called Monarch that
07:35looked at a women who had early stage
07:38breast cancer that had some high risk
07:41features such as four or more involved
07:44lymph nodes or one to three involve
07:46lymph nodes with other high risk
07:49features like grade or size of the tumor,
07:52large tumors,
07:53and it was a big trial with over 5000 women.
07:57And essentially randomize those
07:58women to endocrine therapy.
08:00On the left you can see ET with a
08:03particular cyclin dependent kinase
08:05inhibitor called abemaciclib,
08:07or endocrine therapy alone.
08:08So half the group got integrant therapy,
08:11half the group got ended.
08:13Contrary with this cyclin
08:15dependent kinase inhibitor,
08:16and this was a phase three randomized
08:19trial in what you can see where
08:22I put those numbers of 88.7 and
08:2592.2% is we're seeing with a median
08:28follow up about 15.5 months.
08:30But the curves there are
08:32starting to separate,
08:33and we're seeing that the folks who received
08:35the cyclin dependent kinase inhibitor,
08:37some of them,
08:38seem to be doing better.
08:40The absolute benefit was perhaps 3.3 or 3.4%,
08:43but it's early in this trial,
08:45and this is a signal to us that we
08:47might be seeing an important benefit
08:50for some women by adding this agent in.
08:53So I think that right now this
08:55could be an
08:56option for some women with
08:58very high risk features.
08:59I'd like to see confirmatory
09:01trial saying that.
09:02This another cyclin dependent
09:03kinase inhibitors.
09:04There are three that are FDA approved,
09:06but the other two shows similar benefit,
09:09but I was really happy to see this
09:11presented and this was actually a
09:13different meeting called an ECMO
09:15meeting in earlier this year,
09:17which is a sort of a parallel
09:20to our American meeting.
09:22I want to focus just a minute on
09:25another targeted therapy that's
09:26had FDA approval for a few years
09:29in the setting of stage four.
09:31Again, ER positive her two
09:33negative breast cancer.
09:34When this is an agent called El Pela
09:38Sib and this we can see here is.
09:41Did this agent specifically blocks
09:44the Alpha isoform of a protein.
09:47There you can see in pink called
09:50π three kinase.
09:52And if you look at this cartoon on
09:54the out in the outside world where
09:56that orange Circle says growth factor,
09:58these are the proteins that are still.
10:00Emulating cells to grow to divide
10:02to make more of themselves.
10:05And can we get at that particular cells?
10:08Cell mechanics?
10:08Can we get that in block it to try
10:12to prevent these cells from either
10:14moving through endocrine therapy?
10:16Or can we make integrant therapy,
10:19you know,
10:19work better and so that's kind
10:22of what we're looking at here.
10:24What we've seen is that in the Stage 4
10:28setting for a particular subtype of women.
10:31These agents can be very effective and
10:33that was a trial called Solar One,
10:36and in that trial again almost a
10:39doubling of disease free survival for women,
10:41you know with the you know with this
10:45agent and what we've seen is that.
10:48You know about 40% of women with
10:51PR positive her two negative
10:53advanced breast cancer Harbor
10:55this mutation so L pelis.
10:57It really is in a way a
11:01targeted therapy getting at a.
11:04A regulation problem where the
11:06cells are sort of hyper stimulated.
11:08They have a mutation in this gene.
11:10This mutation is permissive for
11:12cell growth and cell division
11:14and so adding it you know and
11:16it's not an uncommon mutation,
11:18it's in 40% of folks with PR
11:21positive her negative breast cancer.
11:23So hope rugo at UCSF had said well
11:25and we look specifically at this
11:27subgroup that has you know this
11:29mutation in already has seen that
11:31cyclin dependent kinase inhibitor that
11:34we talked about a while ago because.
11:36As our newer therapies coming to play,
11:39we're trying to understand the
11:40influence of a prior treatment
11:42on a subsequent treatment.
11:44So the question the Doctor
11:45Rugo is asking was well,
11:47since cyclin dependent kinase
11:49inhibitors that we looked at earlier
11:51since that standard of care for
11:53women with advanced ER positive
11:55her two negative breast cancer.
11:57What about women who have
11:59been exposed to that?
12:00Will they still respond to this new agent?
12:03Help Ellis,
12:04if in the context of this
12:05π three kinase mutation,
12:07if they had been exposed to
12:09the cyclin dependent kinase
12:11inhibitor and I was very happy to see that
12:13the grass here look very similar between her,
12:16the original solar one trial that
12:18was published a few years ago,
12:21and this trial called by Leave,
12:23where if you can look at the graph with
12:26the sort of vertical lines going down?
12:29That would suggest a response in
12:31terms of decreasing size of tumor in
12:33the grass almost mimic each other,
12:35so they're sort of saying that, well,
12:38we do believe that this agent is going
12:40to be effective in women who have had
12:43a cyclin dependent kinase inhibitor,
12:45and so you know someone coming
12:47through with standard therapy,
12:49ER positive disease,
12:50stage four disease,
12:51getting endocrine therapy,
12:52and a cyclin dependent kinase inhibitor.
12:54If they have this π three kinase mutation,
12:57this is a very viable.
12:59Option for them to go forward and
13:01again a doubling of the disease.
13:03Free survival rate so you know
13:05moving forward trying to get beyond
13:07endocrine refractory disease.
13:08So to me that was very hopeful.
13:12So I wanted to transition for a minute
13:14and just spend a few minutes looking
13:16at some clinical trials we have up
13:18and running at Yale and some of the
13:21focus that were that we're looking at.
13:23And you know,
13:24part of what we understand with cancer is.
13:28You know lifestyle exposures and one
13:30of the questions that were trying
13:33to look at is exemplified in this.
13:35Be well trial.
13:36The PR here is Doctor Sands and
13:39this is a trial looking at saying
13:41you know is weight loss after
13:44being diagnosed with breast cancer.
13:46You know can that affect outcome?
13:48So this is a very large trial across the
13:51country in women are being randomized
13:54to either you know no intervention or
13:56an intervention with counseling about diet.
13:59And weight loss and seeing if that translates
14:02into an outcome of benefit for these women.
14:04So this is an important important study.
14:06We know that women coming
14:08in with breast cancer,
14:09if they are considered,
14:10you know clinically overweight.
14:11You know,
14:12sometimes their outcome that some
14:14data supporting the fact of their
14:16outcome might not be as good
14:17as women who are a bit leaner,
14:19so we're trying to understand that better.
14:22This is a trial called the ABC trial,
14:25and looking at aspirin in early stage
14:28breast cancer and the question being
14:31asked here in Doctor Fishback as the
14:34Pi of this trial we we really have a
14:36deep resource of multiple oncologists.
14:38We're focusing on breast cancer.
14:40Yale and I think that really delivers.
14:44Innovation and quality care to our patients.
14:47Know aspirin and other agents like
14:49aspirin had been looked at in multiple
14:52malignancies for potentially, you know,
14:54preventing or decreasing risk,
14:56and this is a trial asking the question.
14:59Well,
15:00there's a lot of basis to consider this
15:03question as very relevant question.
15:05Could the addition of aspirin affect outcome?
15:08Would women potentially do better?
15:10So this is a very real relevant
15:13trial for us
15:14as well. I just left a few other trials.
15:18Alot of these happen to be national trials,
15:21but just to look at the top three,
15:24one looking at different molecular changes
15:26in a womans breast tumor and then randomize
15:30a different therapy before surgery.
15:32Based on what those with
15:33the molecular profile,
15:35the molecular landscape might look at again,
15:37doctors, Santas, the Pi for that trial.
15:41Another trial you know,
15:42perhaps like that Monarch trial?
15:44Looking at cyclin dependent kinase
15:46inhibitors in early breast cancer trial
15:48called Natalie using an alternative cyclin
15:50dependent kinase inhibitor riverstick Lib,
15:52and asking the similar question
15:54folks with high risk disease,
15:56would they do better with the addition
15:59of this agent in another trial?
16:01Looking at more advanced disease and Doctor,
16:04Mongolian is the P for that
16:06trial and that trial.
16:08Asking the question,
16:09you know we follow folks with advanced
16:11disease stage four disease with serial scans.
16:14How are we doing?
16:16Is the patient responding to
16:18treatment tumor markers guide us?
16:20Can they influence when we order CAT scans?
16:23Can we do less image Ng exposed women to
16:26less radiation and get similar outcomes?
16:29So a lot of a lot of interesting
16:31trials from different perspectives.
16:34And just to mention that more and
16:36more in the advanced cancer setting,
16:39we're looking to understand the
16:41molecular landscape, so we want to.
16:43Study the the genetics of the tumor
16:46by a biopsy and then sometimes
16:48by what we call a liquid biopsy.
16:51Getting a blood sample and looking
16:53for circulating tumor DNA.
16:55And we're doing that more and more
16:57to try to tailor our treatment
17:00to the most effective therapies.
17:02And this is becoming commonplace for us.
17:05And this is a trial that one of
17:08our lead researchers Doctor Push
17:10Die is going to be the Pi of.
17:13And this is a trial in early stage
17:16disease and asking the question.
17:18Well if we follow women on endocrine
17:20therapy after they've had their
17:22surgery and we've had other
17:24treatment in the agement setting.
17:26So after surgery,
17:27as you know when when someone say on,
17:30you know in Aromat ACE inhibitor.
17:35If we check their blood intermittently
17:38looking for circulating tumor DNA,
17:41if we see a certain signal as defined
17:44by the investigators and we acted
17:47on that signal to change treatment,
17:51say from typical adjeman
17:52endocrine therapy to adding, say,
17:55an agent like fulvestrant into
17:57cyclin dependent kinase inhibitor.
17:59For instance, do these folks do better?
18:03So again, trying to get it back question of
18:06if we come in early with different treatment,
18:09adding a second agent you know will our folks
18:11do better in terms of disease recurrence.
18:14I'm very eager to see this trial
18:16begin as well and I wanted to briefly
18:19touch on you know what might be new in
18:22genetics and how this could affect you.
18:24Know some of our patients in the
18:27clinic and some folks who have certain
18:29hereditary risk so we know that.
18:32Our folks have inherited ABRC A1 or BRC A2.
18:36Mutation has some special issues with
18:38tumor DNA repair and we call that
18:41homologous recombination deficiency.
18:43We know that some of these cancers are
18:46more challenging in terms of double
18:49stranded DNA repair because we know
18:52that cells are always having trouble,
18:54and if they can't,
18:56you know if they can't repair themselves,
18:59they would have a signal too.
19:02Parrish,
19:02and so we want to try to take
19:05advantage of maybe an inherent
19:07weakness within the BRC A1 cell.
19:09In this class of drugs
19:10called PARP inhibitors,
19:11I put two in here elaborate
19:14and tell is Zopa rib,
19:15which are FDA approved for advanced
19:18cancer that have been looked at in trials
19:20in the stage for setting for women
19:23with BRC A1 and B RCA two mutations
19:25and their effective and their helpful.
19:27And they're part of our standard treatment
19:30regiment for folks who have burst.
19:32My 2 mutations and one of the questions
19:35that Nadine Tung asked at ASCO this year was,
19:38well,
19:39you know,
19:39what about folks who might have
19:42other hereditary mutations beyond
19:43BRC A1 and B RCA 2?
19:45Because we're finding there are
19:47other high penetrance genes that can
19:50increase the risk for breast cancer
19:52with these people benefit from.
19:54The addition of a PARP inhibitor.
19:57And what about folks who have
19:59acquired mutate?
20:00Susan BRC A1 and BRC,
20:02two so these are folks who don't
20:04have hereditary breast cancer,
20:06but there are tumor cells have acquired
20:08mutations in those same genes.
20:10OK,
20:10and so the question is almost
20:12like Achilles heel question.
20:14Well, if the cell has a problem with repair.
20:17With one mechanism,
20:18because we know our cells are smart,
20:21so they've created multiple.
20:22You know,
20:23evolution is created multiple ways
20:25for cells to repair themselves.
20:27If we take out the single strand DNA
20:29repair mechanism with PARP inhibitors,
20:31could that lead to cancer cells perishing?
20:34We call that concept synthetic
20:36lethality and so this was a trial
20:38where folks with other mutations
20:40and I just want to highlight what
20:42we thought were the seminal aspects
20:45of this trial.
20:46There's a gene called Pal B2,
20:48partner and localized, or V RCA two,
20:50and it's a gene that also, when inherited,
20:53can increase the risk for breast cancer,
20:56and so in the hereditary setting.
20:58It was significant response with
21:00PARP inhibitors to the folks
21:02who had the PAL V2 mutation.
21:04So to me that that's getting
21:06very close to saying well,
21:08folks who have breast cancer in the
21:10context of this mutation like BRC A1B,
21:13RCA two are candidates for a PARP inhibitor
21:15was also very interesting in the middle.
21:18Here is it folks would acquire what we
21:21call a semantic BRC A1-AB or C2 mutation.
21:24They too seem to have an excellent
21:26response rate to these agents
21:28in the advanced cancer setting.
21:30So this was interesting and I think
21:32it's going to be relevant for us and
21:35just to mention that's in contrast
21:37to folks with an ATM or check two
21:40mutation to other genes that can be
21:42associated with hereditary breast cancer.
21:44Those folks didn't seem to benefit, OK?
21:46So I found that very interesting
21:48and one of our investigators,
21:51Doctor Larosa at Yale,
21:52has a trial at trying to mention this
21:55trucks and it's very relevant for our
21:57folks with germline mutations in V RC1BR,
22:00C two and you'll hear more about
22:03checkpoint inhibitors from doctoral Garo.
22:05But this is a trial saying well if we have
22:08folks who have benefit from a PARP inhibitor.
22:11If we add a checkpoint inhibitor might
22:13they do better 'cause there's some
22:16very interesting science behind that.
22:18Suggesting that those medicines could
22:20work very well together in our patients.
22:23So for me it was a Goodyear,
22:26a hopeful year looking at ways
22:28to overcome enterkin resistance.
22:30Some improvements as relates to how
22:32we understand hereditary cancer
22:34in the treatment thereof.
22:35And this is just a slide from the
22:38summer of some women that I know
22:41in Westerly who are doing yoga at
22:44sunrise on the beach and for me
22:47it's sort of symbolized hope.
22:49I do have great hope for this.
22:51I wanted to share that with you.
22:53Thank you.
22:55That was fantastic.
22:56Loved love that last slide
22:58and obviously all the data and
23:01the trials that are underway,
23:02especially here at Yale and Smilow.
23:05Next, we're going to move to
23:07Doctor Mina Moran and discuss the
23:09advances in radiation therapy
23:10and some of the really exciting
23:13techniques that are out there now.
23:28You're on mute.
23:34Is still on on mute.
23:39But while those slides are coming,
23:41there was a question about 100.
23:43It was from Pam regarding 100%
23:45breast tissue density and how
23:47confident you could be an image Ng.
23:50I think that's a fantastic question.
23:52We're going to absolutely get that
23:54in our question and answer session.
23:57And also, what are the signs
23:59and symptoms of breast cancer?
24:01And I think really super relevant questions.
24:03So with no further ado,
24:05Doctor Moran, professor and director,
24:07radiation Oncology at Yale.
24:09Thank you, I apologize for that.
24:11I'm having some technical difficulties today,
24:13so I'm going to be talking to you about
24:17radiation and just to give you an idea,
24:19you know one of the things I want to
24:22talk about is just the general principles
24:25of practices for breast radiation,
24:26such as the role of radiation
24:28in breast conservation therapy,
24:30the role of radiation after mastectomy,
24:32and the use of radiation
24:33in the palliative setting.
24:35I want to talk about radiation,
24:37what it is makes a lot of patients that
24:39come for consultation don't really have an.
24:42Idea of what it is or what it does.
24:45And Lastly,
24:46I want to talk about some of the
24:48technological advances that we now are
24:50using routinely in our practices to
24:53decrease normal tissue.
24:56So when a patient is newly diagnosed
24:59with early stage breast cancer,
25:01one of the major decisions that they face is
25:05the choice between Ms Ectomy or lumpectomy.
25:08If they are a candidate for a lumpectomy.
25:11And this shows long-term survival,
25:14following a lumpectomy with
25:15radiation versus the mastectomy.
25:17And as you can see here,
25:20that the outcomes in terms of
25:22long-term survival are equivalent.
25:24And this is nevertheless a persistent myth.
25:27But Patience feels that once the
25:29breast is a fully removed that
25:32their outcomes may be better,
25:34but unfortunately that isn't it.
25:36Fortunately, or unfortunately,
25:37they're not.
25:38It is not the case,
25:40and what we see is that more and
25:43more women over the last decade or
25:46so have been choosing mastectomy
25:48over a breast conservation.
25:50Ultimately that the outcomes are the same,
25:53and So what are the indications
25:55for when a patient may require?
25:58Radiation,
25:58the most common indication is in the
26:01use of breast conservation therapy,
26:03which is defined as limited surgery to
26:06remove the tumor with negative margins,
26:09and that's followed by whole breast
26:12radiation with an assessment of the
26:14lymph nodes and breast conservation therapy.
26:17As I said,
26:18is a standard alternative to mastectomy
26:20for early stage breast cancer and
26:23provides equivalent long-term outcomes
26:25up to 25 years for eligible patients.
26:28So after.
26:29Lumpectomy the alternatives
26:30to whole breast radiation,
26:32can also be a partial breast
26:34radiation therapy plan,
26:36where the lumpectomy cavity is outlined.
26:39And we're treating just that
26:41small portion of the breast.
26:43This approach is actually quite promising.
26:47Appears to have good cosmesis,
26:49but the studies are newer than the
26:52traditional whole breast radiation
26:54and they have significantly shorter
26:55follow-up and so currently it's only
26:58being offered for selected low risk patients.
27:00And then Lastly,
27:02there's one group of patients where
27:04we routinely offer them radiation,
27:07omission,
27:07or just having the lumpectomy with
27:09a no additional aggregate radiation.
27:11And this is for patients over the
27:14age of approximately 65 to 70 who
27:17haviar positive tumors that measure
27:18less than two to three centimeters,
27:21and who have negative nodes,
27:23and who are willing to commit
27:25to tamoxifen for five years.
27:27And what we
27:28tell these patients is that they
27:30their risk of. The cancer coming
27:32back within the breast is higher,
27:34but if it does come back they can
27:36ultimately have a mastectomy and so
27:38therefore there is no survival difference.
27:43What are the indications for a after
27:46a mastectomy to do radiation well,
27:49radiation is typically offered in the post
27:52mastectomy setting for high risk patients,
27:55and it's used to sterilize microscopic
27:58disease on the chest wall.
28:00In regional lymph nodes.
28:03Typically the radiation is a delivered entire
28:06chest wall and any lymph nodes at risk.
28:09The patients that we consider
28:11for most mastectomy radiation are
28:14those who have positive nodes.
28:16Those who have positive margins if
28:18they have tumor that involves the skin,
28:21or if they have a tumor that
28:23measures of five centimeters.
28:28So whether it's.
28:31Text me or post mastectomy radiation.
28:34It's important to recognize that
28:36radiation is very safe and effective
28:38and is much better tolerated than it
28:42was years ago due to the advances that
28:45we've made and radiation generally
28:47reduces local and regional recurrences
28:49by approximately 60 to 70%, which is a
28:53relative risk reduction of about 2/3.
28:57In certain subsets of patients,
28:58radiation is also associated with an increase
29:00in survival and could be as high as 10%,
29:03and this is particularly true
29:05of the younger patients who have
29:07a very long life expectancy.
29:10The treatment is almost always given
29:12after chemotherapy and the treatment
29:15duration of radiation is specific to
29:17the patient and it can be as good as six
29:20weeks out from from beginning to end.
29:24So the last major an indication for radiation
29:27is for patients in the metastatic setting
29:30or in the recurrent disease setting.
29:33Or a patient has disease
29:35that's causing symptoms.
29:36In these situations the radiation is that
29:38delivered is given in a pallet of way,
29:41meaning that it's used to alleviate
29:44the symptoms that the patient
29:45might be experiencing,
29:47and it's highly effective.
29:48It can be up to 70 to 90% of
29:52patients do resport report that
29:54they have a very good pain control.
29:57But the fractionation in
29:58differs significantly.
29:59Can be anyway?
30:00From 10 to 15 treatments or as
30:03little as one to two treatments,
30:05depending on the site and the
30:07performance status of the patients,
30:09and typically it's used for things
30:11like bone lesions, brain metastasis,
30:13soft tissue masses or even chest
30:16wall recurrences.
30:17So just an important point.
30:19Lastly,
30:19for all treatment of breast cancer,
30:21I think it's important to remember
30:23that every breast cancer is different,
30:25and so the biology is different in every
30:28case as well as patient related factors
30:30that that a physician has to consider.
30:32In addition,
30:33we have to look at the efficacy of
30:36the treatment as well as the toxicity
30:38and then look at the risks versus the
30:41benefits to make sure that it's it's
30:43worth the treatments for the patient.
30:45So in addition to the doctors.
30:47Recommendation for their whether
30:49or not to deliver radiation and
30:51other important components that
30:53sometimes gets neglected but should
30:56be discussed is the patients of
30:59personal preferences and what they
31:01want to do and how they would receive.
31:04So now what is radiation?
31:06Radiation is a high energy X Ray beam,
31:10not very different than a chest
31:12X Ray or cat scan.
31:14They all use ionizing radiation,
31:16but the magnitude of the energy
31:19is significantly greater,
31:20up for therapeutic radiation and
31:22ultimately what it does is it causes
31:25damage to any of the cells that are
31:28in the radiations pathway and so
31:31within our field of radiation oncology.
31:34Our goal is to try to use.
31:37The radiation to minimize the
31:39chance of the cancer coming back
31:41locally or regionally.
31:42And we do this by trying to individualize
31:45the beams to the patients anatomy
31:47and target the areas at risk for
31:50recurrence and minimize the dose to
31:52the normal tissue wherever possible.
31:56So how does radiation work while the
31:59individual X Ray beams target the
32:01DNA and normal cells as well through
32:04a direct and indirect mechanism?
32:06That's a little bit too difficult
32:09to explain in this short session,
32:12but ultimately what happens is that
32:14the the radiation causes damage
32:16to the DNA of any cell,
32:19and by doing this it ultimately
32:22prevents the cells from replicating
32:24unless they can repair themselves.
32:27And So what are the what are
32:30the exact types of damages?
32:32All different kinds but but the the
32:35damages are typically such that the
32:38cancer cells are not able to recover from it,
32:42whereas normal cells such as
32:44our skin lung tissue,
32:45our breast tissue is able
32:47to recover and for this
32:50reason it leads to cancer cell
32:52death when the cells try to
32:55reproduce or replicate, whereas.
32:57The normal tissue has the ability
33:00to repair and seal off and then
33:03continue with its normal life cycle.
33:07So when a patient comes in for radiation,
33:10sometimes they think that
33:11they're going to start radiation.
33:13The date if they have the consultation,
33:15and this is just to show you that there's
33:18actually a process that we follow.
33:19The patient first needs to undergo a see
33:22T simulation an it's a multi step process
33:24where we put the patient on the table.
33:27We immobilize them to make sure that we can
33:30reproduce their positioning on a daily basis.
33:32For the treatments we add some
33:34markers to their skin on their
33:36skin and then we get the scan.
33:38This is what one of the
33:40immobilization looks like.
33:42It is a vac lock with a breast board.
33:45Patients are required to put their
33:47arms up and so for this reason another
33:49important important point is that
33:51when patients come to radiation,
33:53they should be able to raise their
33:56arms comfortably and keep them up
33:58for at least 20 to 30 minutes in
34:01order for the CAT scan and the
34:04entire simulation process to occur.
34:07And so this is what the radiation
34:09feels look like.
34:10And this is just a schematic.
34:13But basically what happens is the
34:15head of the machine moves to the to
34:18one side of the breast or the chest
34:20wall tissue and it treats it and
34:23then moves to the other side and
34:25treats the other side of the breast.
34:28And by doing this we're really
34:30skimming the chest wall and not
34:32penetrating from the front to the
34:34back an in this way we're really just
34:37treating the superficial a tissue.
34:39Which includes the breast tissue.
34:42Here are the wires that we put on to
34:45clinically delineate what we want
34:47to make sure that we're covering
34:50an right underneath you see the two
34:53CT scans and in the pink you have
34:56the breast volume.
34:57The yellow that you see there is
35:00the lumpectomy volume and on the
35:03scan to the left side of the screen
35:05you see the three little areas that
35:09are outlined are your lymph nodes.
35:11In the axilla and the red line that I drew,
35:15is that tangential beam?
35:16So just to show you that we were
35:19able to cover a good portion of the
35:22breast and the level one Level 2
35:24and Level 3 lymph nodes with just
35:27a tangential beam alone?
35:29So ultimately this 3 dimensional
35:31technology with the use of CAT scans
35:34and looking at it at every different level,
35:37it allows us to contour the beam
35:39to an individual patients anatomy
35:41and it allows us to deliver precise
35:44and focused radiation beams.
35:46So what does radiation target
35:48and what do we try to target?
35:51Most patients who undergo breast
35:53conservation have their whole
35:54breast treated at this time.
35:56We may or may not include nodes
35:59if the patient.
36:00If it's indicated for the patient,
36:02for example, if they have positive nodes,
36:05we often will include the regional nodes.
36:07After the mastectomy,
36:08we treat the chest wall and
36:10a more often than not,
36:12because these are higher risk patients,
36:14they will have their regional nodes treated.
36:17And this is what the fields
36:19look like on the skin.
36:21So this is just a schematic to show you what
36:25the delivery of the tangential beams are.
36:28First, there's the medial beam or
36:30the medial part of the treatment,
36:33so you have the beam and sub beams within it,
36:37which are tailored to the
36:39individual patient and delete.
36:40Deliver the radiation medially.
36:42Then the beam moves into
36:44the lateral position,
36:45so the height of the machine
36:48moves to the lateral side of the
36:51patient and again similar beam.
36:53Delivers the tangential field and sub
36:55beams as well and ultimately together.
36:57What that gives you is a dose distribution
37:00that looks like what that purple
37:02and the yellow there are covering.
37:05So you're covering a good part of almost
37:08all of that breast tissue with a very
37:11little amount of lung or heart in the field.
37:15And so the goal is,
37:17as we're doing this treatment,
37:18planning is to design the beams in such a way
37:21that we treat the breast and the chest wall,
37:24with or without the lymph nodes,
37:26and we minimize the radiation
37:28to the normal tissue.
37:29And so we have a lot of tools
37:32that we are able to use,
37:34such as.
37:34Once we get the CAT scan,
37:36we can three dimensionally recreate
37:38the skin surface as well as the
37:40three dimensional internal surface
37:42so that we are able to see exactly
37:44where these beams intersect.
37:45And also then be able to change the
37:48beam a little bit in order to make sure
37:52that we're covering what we need to cover.
37:54The things that we worry about,
37:56the most critical things that we worry about
37:59are the the heart in the lung obviously,
38:02and sometimes the liver.
38:03And so we have two important tools
38:06that we use regularly to minimize
38:08that dose to the heart and lung.
38:10The first one is the deep inspiration,
38:12breath hold technique and the
38:14other one is the prone breast board
38:16technique and I'm just going to
38:18briefly talk about both of those.
38:20The deep inspiration breath
38:22hold technique allows a patient
38:24when they take a deep breath.
38:25Their chest wall moves away from
38:28the heart and and in doing so and
38:31with the diaphragm going down,
38:32what you have is more room for that
38:36tangential beam to get in there
38:38and to be able to treat without
38:40exposing the hearts and also it
38:42reduces the amount of a lung volume.
38:45So this is just an example to
38:48show you in a patient.
38:50On the left is the free breathing scan.
38:53On the right is the breath hold.
38:56In in red you see the heart contour,
38:59how much the heart shape changes in
39:02this particular patient when she
39:04holds her breath and that really
39:06allows us to get into the chest wall,
39:08the breast tissue and nodes,
39:10and miss the heart.
39:13This is just a cross section of
39:16that showing you
39:17again the decreased heart dose on the
39:19left you have the free breathing on the
39:22right you have the breath hold and how
39:25significant that change in anatomy is.
39:27Using this breath whole technique.
39:29So then the question is well, OK,
39:31fine, you do that on the CAT scan
39:34at the time of CT simulation.
39:37But what do you do day today for
39:39the six weeks of treatment that
39:41you're bringing the patient?
39:43In every day, well,
39:45we have very sophisticated lasers
39:47within the treatment room that
39:49project onto the patients skin and
39:52determine the exact position that
39:54the body contour should be in when
39:58the patient takes that deep breath.
40:01And these reference points are locked
40:03into our record and verify treatment system,
40:06and so the machine only turns on and
40:08delivers the radiation when the patient
40:11is in that exact precise breath hold,
40:14and this is within 3 millimeters,
40:16so anything more than 3 millimeters,
40:18the machine will not turn on and the patient
40:22holds their breath as long as they can,
40:25the machine delivers.
40:26It does what it's supposed to do as soon
40:30as the patient releases their breath.
40:32The machine turns off and then the
40:34patient catches up on their breath
40:36and you repeat the cycle until
40:38the entire treatment is delivered.
40:40So this is just a data showing you
40:43just one study looking at the IBH in in
40:46patients who have who do free breathing.
40:49These are just some cardiac parameters.
40:52You see that only about 50 to 60% with
40:55free breathing can avoid the cardiac
40:57structures to what is considered acceptable.
41:00With deep inspiration breath hold
41:02technique that increases to about 97%.
41:04So that's it's it's remarkable that it works
41:08very well in the vast majority of patients.
41:12But what about that last 3% of patients
41:15where the DB H doesn't work well?
41:17We have another technique.
41:19It's not as precise,
41:20but it does work very well.
41:22It's the prone board and what
41:24we do is we instead of having a
41:27patient patient on the left there
41:29with their laying on their back,
41:31you can see that their heart
41:33is clearly in the field,
41:35will put them in the prone position and we
41:38use gravity to have that breast fall forward,
41:41and it allows us.
41:43To treat the vast majority of the
41:45breast tissue in the chest wall
41:47without having to treat the heart,
41:50and so this is our alternative
41:52method for decreasing heart dose,
41:54and it works quite well as well.
41:56This is what the breast board looks like.
41:59Again,
42:00the ipsilateral breast or the side
42:02that we're treating hangs down the.
42:05Your side is pushed up and out of the way.
42:08We do similarly outline the volume of the
42:11breast tissue and the lumpectomy cavity.
42:13And an important point is that if a
42:16patient has a tumor that was originally
42:18very close to the chest wall,
42:21that would be a patient.
42:22For example,
42:23that we would not want to do breath holds.
42:26I mean not do prone breast board on
42:29because you are skimping a little
42:31bit on the very very posterior
42:33aspect of the chest wall there.
42:35But in the vast majority of
42:38patients that we do it in it,
42:40as long as their appropriately selected,
42:42it's a very effective technique as well.
42:45So in summary, radiation is an
42:47essential component to the multi
42:49disciplinary approach of breast cancer,
42:51and as I mentioned to you for
42:53early stage breast cancer,
42:55breast conservation therapy
42:56is equal to mastectomy,
42:58meaning that there is no difference
43:00in survival rates and for this reason
43:03I like to stress that mastectomy
43:05shouldn't be chosen by patients.
43:07Under the false pretense that
43:08they're going to have better outcomes
43:11by removing the whole breast,
43:13because this isn't the case.
43:15Also, don't choose mastectomy just
43:17to avoid radiation because you don't
43:19want to go through five weeks or
43:21six weeks of radiation because even
43:24after mastectomy there are going
43:25to be patients who are going to
43:28require postmastectomy radiation.
43:29And Lastly that with the current
43:32technology and the advances that we have,
43:34radiation has really become quite
43:36safe and effective, it does.
43:38Decrease local and regional
43:39recurrences by about 2/3.
43:41There's also a survival benefit
43:43in some patients,
43:44and it's much better tolerated
43:46than it was years ago,
43:47so I often will have patients
43:49who come to me and say,
43:52Oh my mother had radiation 20 years ago,
43:54but it was awful.
43:56It's not the same as it was years ago.
43:59Our technology has advanced so
44:01much that the vast majority of
44:03patients tolerated very well,
44:04and if you need it,
44:06it is not necessarily something to fear so.
44:09Thank you for your time and thank you
44:12for calling in this late in the evening.
44:14Thank
44:14you doctor Mario that was fantastic.
44:16Loved it. I actually learned a lot
44:18and was almost holding my breath
44:19while you were talking about.
44:23And now last but certainly
44:25not least Doctor on couple
44:26Garo talking about again more.
44:29You know the amazing changes that
44:31are ongoing in medical oncology.
44:33We've gotten a whole slew of questions,
44:36so once you're done,
44:37I'll be asking our panelists for
44:39their thoughts and opinions.
44:45Good evening, it's a privilege for
44:47me to be part of the smilow shares,
44:49and Moreover to be part of the same 323.
44:53Teammates smile, water for the doctor.
44:56Legare and Doctor Moran.
44:57I would like to share the screen so
45:00Doctor Moran would you mind to Unshare?
45:04Yeah. I have unshared.
45:09Stop sharing. Yup, there you go.
45:15OK.
45:30OK, sorry. I am.
45:41So in my talk I'm going to focus
45:44on some novel treatment options
45:46in her to positive and triple
45:49negative advanced breast cancer.
45:51We do know that not every case of
45:55breast cancer is the same as doctor.
45:58Legare mentioned.
45:58Approximately 70% of the breast
46:00cancers are hormonally driven.
46:02However, there are other cancers.
46:06That may have a different driving
46:09pathway that our is called her two
46:13and they represent approximately
46:1520 to 25% of all breast cancers,
46:19while 1015% of breast cancers.
46:22I'm sorry.
46:24Are considered the triple negative.
46:25They do not have expression for estrogen,
46:28progesterone, or hard to,
46:30and it is important to know
46:32which subtype of breast cancer
46:35you're dealing with because.
46:37Survival and prognosis is different.
46:39The best prognosis is for the
46:42hormonally driven cancers,
46:43but the her two positive,
46:45either with your positive ITI or
46:48concurrently are negativity as
46:50well as the triple negative breast.
46:53Cancer may not have the same
46:55excellent prognosis.
47:00In the last several years we've had
47:03tremendous advancements in the treatment
47:05of a triple negative breast cancer,
47:07and her two positive breast cancer,
47:10and I'm going to mention two
47:13such advances for each subtype.
47:15What is her two positive iti we do know that.
47:19Breast normal breast cells and
47:21most of the breast cancer cells
47:23do have a certain number of.
47:26Her two receptors,
47:27her stands for human epithelial
47:29receptor and in that class we have four
47:33different categories for breast cancer.
47:35The her two are the most important.
47:39So this had two receptors,
47:42are transmembrane proteins
47:43and when are lagging,
47:45the growth factor attaches to the receptor.
47:48It induces the dimerization.
47:50The pairing of that
47:51receptor with another one,
47:53and that in turn will activate the
47:56internal part of the receptor.
47:59This code of tyrosine kinase and it
48:02will trigger a sequence of events
48:05that would lead to activations
48:07of pathways and genes inside the
48:10nucleus and ultimately lead to.
48:13Pro growth to proliferation in
48:15approximately 25% of the breast cancer.
48:18We have an over expression of her
48:21two receptors and or over expression
48:24of the genes the her two genes
48:28in the nuclei and that leads to
48:31an exuberant activation.
48:32If you may say so of the.
48:38Proliferative pathways inside the
48:40cancer cells that could lead to a more
48:43aggressive growth and cancer spread.
48:45And the important of this pathway
48:48was recognized in the 1980s.
48:51And while this pathway confers the
48:55cancer monographic aggressiveness,
48:56it also gives us the opportunity
49:01to interact with it.
49:03Two to treat and a big component of
49:08that improvement in the breast cancer
49:12mortality that Doctor Legare mentioned is.
49:16Basicaly due to the advancement in the
49:19her two positive breast cancer treatment.
49:22So in the late 1990s,
49:24the first drug that was approved
49:27by FDA was transducer MA.
49:29This is a monoclonal antibody that attaches
49:33to the her two receptor and basically
49:36blocks the proliferative pathway there are.
49:40Several mechanisms it could
49:42also induce the degradation of
49:44the receptor prevents sharing,
49:47but nevertheless.
49:49The plastic so mad made a tremendous
49:52difference in the overall survival of
49:55patients with metastatic disease and
49:57later it was brought to the earlier.
50:01Stages of the breast cancer and
50:03significantly improved the chance
50:05for cure and decrease risk of
50:08recurrence for early stages.
50:09Breast cancer in 2012 we had the advent
50:13of pertuzumab that blocks the pairing of
50:16the her two receptor with the her three.
50:19This is the strongest.
50:24Excuse me still way of stimulating
50:28the her two pathway and together
50:31with transducer mom again broad
50:34additional benefit for metastatic
50:36breast cancer cases patients and now
50:40it's also approved for treatment of
50:43patients with early stages breast
50:47cancer before their surgeries.
50:50A newer concept is the antibody
50:52drug conjugate,
50:52and I'm going to talk in more detail.
50:58In the next few minutes.
51:00So, this monoclonal antibodies
51:02are large molecules that act
51:05outside the cell membrane,
51:07but we also have a class of drugs
51:10that are called targeted tyrosine
51:12kinase inhibitors that are smaller
51:15molecules taken by mouth that could
51:19basically block the thyrogen kinase.
51:21The internal part of the heart receptor,
51:25and by doing that it basically stopped.
51:28They stopped this activation of the.
51:31Metabolic pathways and.
51:35They do have slight differences,
51:37but there are some slight differences
51:39between the three compounds and
51:41the newest one is to cut in it,
51:43and again, I'm going to talk
51:45a little bit later about it.
51:50So the. Antibody drug
51:53conjugate's represent them.
51:56Significance advancement in the treatment of.
52:01Breast cancer and basically the
52:04antibody molecule that is transducer
52:08map is loaded with several small
52:12molecules of a potent cytostatic
52:15or potent chemotherapy that is
52:19delivered directly to the cancer cell
52:23overexpressing her two receptors.
52:26So it's a targeted chemotherapy
52:29delivery system.
52:31So when it after it attaches
52:33to the receptors,
52:35it gets internalized in what we
52:37call an endo zone the and after an
52:40activation of certain enzymes in
52:42the what it becomes now the lysosome
52:45the chemotherapy medication is.
52:50Released inside the cells
52:52and kills the cells.
52:53So different antibodies have
52:55different abilities to release,
52:57less or more of this chemotherapy molecules,
53:01and we do know that the sum of
53:04the chemotherapy can diffuse
53:06into the neighborhood.
53:08It can diffuse outside the cell and
53:11actually killed some other cells
53:14in the neighborhood that may not
53:16be so strongly her two positive.
53:20So this is what we call a
53:24bystander killing effect.
53:25So the first antibody drug, conjugate,
53:28that was approved by FDA in 2012,
53:32was trastuzumab, khamsin, or PDM,
53:35one and basically it's a molecule
53:37of transducer mob with 3.5
53:40molecules of maintenance,
53:42and that is a very strong cytostatic
53:46that would be too toxic to be.
53:51I mean to be used as a treatment on its own.
53:54So this medication made significant
53:57improvement in the outcome of metastatic
54:01breast cancer when used in second
54:04line after a patient's progress.
54:08Usually transducer marban pertuzumab plus
54:11attacks in bone backbone chemotherapy.
54:14But as of 2019,
54:17it got FDA approval also for treatment.
54:22Agile and setting up if patients
54:25are treated with trastuzumab
54:27and pertuzumab and chemotherapy,
54:30and they have residual.
54:32Disease at the time of the surgery,
54:36those die hard cells could be
54:39better killed by this targeted
54:42delivery of the chemotherapy.
54:45In December 2019,
54:46FDA gave accelerated approval for a
54:49new antibody drug conjugate called
54:52transducer Map Direct City Cam.
54:55The commercial name is in her too,
54:58and while we're not supposed
54:59to use commercial names,
55:01it's much easier to pronounce.
55:03So compared to TDM one,
55:06this antibody delivers a much
55:09higher payload of chemotherapy.
55:11It has eight such molecules attached to it,
55:16and what happens the linker
55:20that attaches the.
55:22The chemotherapy that is a typo.
55:25I summarize one inhibitor
55:28to the transducer map.
55:31It's cleavable.
55:32Meaning like it then gets cleaved
55:36easier inside the cancer cells and that
55:40accounts for a much higher bystander effect.
55:44In addition,
55:45this molecule has a much higher
55:48affinity for the her two receptors
55:51compared to the Herceptin,
55:53and also to the TDM one.
55:57So.
55:59They approve all his based on
56:02this Destiny Breast 01 trial,
56:05which basically was a single arm
56:08phase two trial that enrolled
56:11112 twelve patients who were
56:14heavily pretreated so that means
56:17they had received number of.
56:20My therapies before the median number
56:23was six where there were patients who
56:25received as few as two and some other
56:28patients who received as many as 29.
56:30And in such,
56:32a heavily pretreated population,
56:34usually the response rate is very low,
56:37but in this is the waterfall plot
56:40analysis and basically each line
56:43represents an individual patient and the
56:46length of this bar or line basically
56:49reflects the depth of the response,
56:52and a picture is worth 1000 words.
56:55You can see that the vast majority of
56:59patients had a shrinkage in their tumor,
57:03so by.
57:04We call it stable disease if it's
57:09shrinkage less than 30% and significant.
57:14Or a partial response if it's
57:17more than 30% and progression
57:20of when it's more than 15%,
57:23so 60.9% of the patients
57:26treated with trastuzumab.
57:27Dirac stickan achieved response rate for.
57:32And 76% of the patients had the control
57:36of their disease at six months.
57:39This response lasted for at least 14
57:41months and not only that, it worked,
57:44but it worked fast with a median time
57:47to response of 1.6 months, which means,
57:51like a little bit more than six weeks.
57:55The overall survival in this
57:57study has not been reached.
57:58The medication is well tolerated mainly
58:01with the neutropenia and some fatigue,
58:03but there is a particular side
58:05effect that requires attention
58:07and it's called interstitial lung
58:09disease that usually presents with.
58:11Shortness of breath and cough and.
58:16On the imaging studies it would
58:18show some ground glass opacity's,
58:20so the doctors do know to monitor
58:23for such side effect very carefully.
58:26Of note,
58:27patients with her two positive
58:29disease have a higher propensity
58:31for developing brain metastases
58:34and such patients are usually
58:36excluded from the clinical trials.
58:39In this best in in 01 trial,
58:4224 patients with stable brain
58:45metastases were included and that
58:47progression free survival was 18 months
58:50and that is absolutely remarkable.
58:53But I am glad to say that there
58:56is another drug that also got
58:59recently approved and that could
59:01give us even a better hope for such
59:05patients with brain metastasis.
59:07And this is the selective tyrosine
59:09kinase inhibitor called Tucatinib.
59:11And as I said before,
59:13it works at the intracellular
59:16portion of the pathway.
59:18So the her two climb patient,
59:21so you had to climb trial randomized
59:24612 patients to chemotherapy with
59:26trastuzumab and keep site had
59:29been with or without Academy.
59:32So some patients receive the catnip.
59:35Some patients receive the possible and.
59:3948 percent of the patients of almost
59:43half of them had brain metastases.
59:48Somewhere stable and somewhere
59:50newly diagnosed but not requiring
59:53immediate treatment and some had
59:56progression after prior treatment.
59:59So the.
60:00In the overall population,
01:00:02there was a significant improvement
01:00:04in the pro Disease Control.
01:00:07What we call progression free
01:00:09survival with 46% reduction in
01:00:11the risk of progression.
01:00:13And that translated into an improvement
01:00:16in the overall survival with 34%
01:00:18reduction in the risk of death.
01:00:24When we look at the patients
01:00:27with brain metastases,
01:00:28the overall response rate was 47%.
01:00:31For patients who had.
01:00:35The Tucatinib treatment versus
01:00:38placebo and that translated into
01:00:40an unprecedented improvement in the
01:00:43progression free survival at one year.
01:00:47Like 75% of the patients were alive
01:00:51and with control of their disease
01:00:55and also in the overall survival.
01:00:58So these two medications transferred
01:01:01him up the Rack City can,
01:01:03and the Ducati need represent
01:01:06major improvements in the
01:01:07treatment of the advanced.
01:01:09Her two positive breast cancer.
01:01:11They are now being studied in more
01:01:14and earlier lines of therapy in
01:01:17opposing ajibon therapy for the.
01:01:22The transducer map the taxi can to
01:01:25replace the TDM one or second line
01:01:29and also looking at their effecting
01:01:32the patullo positive disease.
01:01:34So shifting gears to triple
01:01:37negative breast cancer,
01:01:38we define it by what is what doesn't have
01:01:41by the lack of estrogen progesterone
01:01:45receptors and her two receptors,
01:01:47and it represents 10 to 15% of all
01:01:51breast cancer cases more common
01:01:53in African American patients
01:01:55and those of Hispanic heritage.
01:01:57Younger women.
01:01:58Those who are BRC A1 mutation carriers.
01:02:02We do note that 85% of bracamonte associated
01:02:05breast cancers are triple negative.
01:02:08And Conversely,
01:02:0910 to 15% of the triple negative
01:02:12breast cancer patients have BRC
01:02:14one mutation and they do have
01:02:17a more aggressive behavior,
01:02:19but even triple negative breast
01:02:21cancer is not the same disease.
01:02:24There are different subtypes.
01:02:27Researchers from Vanderbilt University.
01:02:31It's remarkable research and
01:02:33identified several subtypes.
01:02:35There were seven initially,
01:02:36and they were narrowed down to four,
01:02:40and I'm not going to go into details
01:02:43about the specifics of each subtype.
01:02:46But just to mention that there are
01:02:49different genetics and molecular
01:02:51differences and there is extensive
01:02:54research trying to target.
01:02:56Them and find particular.
01:03:00Solutions and treatments for
01:03:03each breast cancer subtype.
01:03:05So we do have breakthrough
01:03:07development in the treatment of
01:03:09triple negative breast cancer,
01:03:12and this is a drug called Sacituzumab movie
01:03:15taken that was approved in April of 2024.
01:03:19Three front of triple negative breast cancer.
01:03:22So this is a targeted antibody
01:03:25drug conjugate similar to transfer
01:03:27some of their practican.
01:03:29But in this case it targets a drop
01:03:33two antigen that was found to be
01:03:36expressed on many epithelial cancers.
01:03:39Such as bladder cancer,
01:03:41breast cancer initially thought to be
01:03:44specific for triple negative breast cancer,
01:03:47but recent research showed that
01:03:50actually it's equally expressed on the
01:03:53ER positive breast cancers as well,
01:03:56so the antibody targets this antigen and
01:03:59antibody has a high payload of chemotherapy,
01:04:03called SN 38.
01:04:05This is.
01:04:07Metabolic product over
01:04:09chemotherapy that we know we can.
01:04:13That is basically used to treat.
01:04:18GI malignancy is mainly,
01:04:20and it's not necessarily part of
01:04:23the armamentarium that we have for
01:04:25the triple negative breast cancer.
01:04:28So it delivers a novel chemotherapy to
01:04:31the triple negative breast cancer cells,
01:04:34and what is also particular about
01:04:37this compound is that the linker
01:04:40is very pH sensitive and that.
01:04:43A has a very.
01:04:49It is released very easily into
01:04:52the cancer cells and also has
01:04:56an important bystander effect.
01:04:59So this medication was approved
01:05:01based on the results of a phase two
01:05:05trial where women were treated.
01:05:08In third line or above and there
01:05:10was a response rate of 35% with.
01:05:14Progression free survival or 5.6 months
01:05:17and overall survival of 13 months.
01:05:20So European Society of Medical
01:05:23Oncology in September 2024 S mom
01:05:26we the results of the central were
01:05:30presented and basically this trial
01:05:33compared Gov Itacon versus single
01:05:36agent chemotherapy in metastatic
01:05:39triple negative breast cancer in
01:05:42women who already had at least two
01:05:46prior chemotherapy regiments and
01:05:48this novel medication was compared.
01:05:52To what ever the physician thought
01:05:55would be the best possible choice
01:05:58for that particular patient.
01:06:01And there was a significant improvement
01:06:04in the progression free survival
01:06:07from 1.7 months to 5.6 months.
01:06:10The and there was also an improvement
01:06:13in the overall survival,
01:06:15so this is the first study that
01:06:18showed an improved survival over
01:06:21standard of care in triple negative
01:06:24breast cancer and the results
01:06:27again are unprecedented and this
01:06:29drug is going to move to.
01:06:33Earlier stages of treatment.
01:06:37It is well tolerated with main
01:06:39side effects being anemia,
01:06:41neutropenia, and diarrhea.
01:06:42That is usually very well
01:06:45controlled with Imodium.
01:06:46So.
01:06:49Using the same concept.
01:06:52That's targeting different.
01:06:56An antigen called leave 1A.
01:06:59There is a drug called the.
01:07:03Look, that is a map that is in
01:07:06clinical trials at and we are
01:07:07happy to say that is open at
01:07:09Yale through Phase one program.
01:07:11And the. We do know that some of
01:07:14the triple negative breast cancer.
01:07:17Do have a low expression of the
01:07:20her two receptors and transducer
01:07:22Moderat stickan is being studied
01:07:25in this setting as well.
01:07:27And the sacituzumab govit econ
01:07:29is also studied in ER positive.
01:07:34Metastatic breast cancer and again,
01:07:36I'm happy to say that we have a clinical
01:07:40trial called tropics to open at Yale.
01:07:44So over the last decade,
01:07:46the advent of immunotherapy has changed
01:07:49Natural History of many cancers.
01:07:52And obviously there was a question,
01:07:55would that make a difference in
01:07:58metastatic triple negative breast cancer?
01:08:01We do know that body has an innate
01:08:04immune system that is supposed to
01:08:07protect us against the invaders
01:08:09against breast cancer cells,
01:08:12and when the normal antigens are recognized,
01:08:15the P cells would come and destroy the cells,
01:08:20however the cancers.
01:08:23Dude, learn to fight back so we do have
01:08:27this checkpoint mechanism that basicaly
01:08:30also has a good role to prevent the P
01:08:35cells of attacking the normal cells.
01:08:38But the. Two more cells take advantage
01:08:40of that by overexpressing body called
01:08:43the program death Ligand and binding
01:08:47the OR pedial one receptor and binding
01:08:50the PD one receptor on the tumour
01:08:53cells and turning off the surveillance
01:08:56of the immune system and by doing
01:08:59that they managed to grow undetected.
01:09:02So Fortunately we do have a new
01:09:04class of drugs that are called immune
01:09:06checkpoint inhibitors that could block
01:09:09either the PDL one receptor or the
01:09:11PD one receptors and by doing that.
01:09:14The T cells are now allowed to detect
01:09:17the cancer cells and destroy them.
01:09:21So several such drugs are were
01:09:24investigated in, particularly in
01:09:26triple negative breast cancer,
01:09:28and this single therapy and first
01:09:31line setting the response rate
01:09:33was not that impressive,
01:09:35maybe only in the low 20%.
01:09:38But what is intriguing is that
01:09:41there are patients that are
01:09:44responders who have very durable.
01:09:47A response and potentially be cured.
01:09:52So.
01:09:54Impassion 130 was the first trial
01:09:58that basically combined pedia.
01:10:01One inhibitor atezolizumab with the
01:10:03chemotherapy backbone of NAB paclitaxel.
01:10:064.
01:10:08Women with the triple negative breast cancer.
01:10:14And or locally advanced,
01:10:18unresectable breast cancer.
01:10:20And. They were treated.
01:10:25And the statistics have
01:10:28showed the significant.
01:10:31Improvement in the duration of the
01:10:34Disease Control of more than two months.
01:10:37But actually the benefit was seen
01:10:40only in the patients who had the PD
01:10:44L1 expression positive ITI using the
01:10:47specific essay called Ventana SP 142.
01:10:50In the clinic,
01:10:52in this particular clinical trial,
01:10:5340% of the patients had
01:10:55the PD L1 positive ITI,
01:10:57but we do know that in real life only 20
01:11:01to 30% of such patients are positive.
01:11:04So the Disease Control translated into
01:11:07an improvement in the overall survival
01:11:11of 10 months from 15 to 25 months.
01:11:15For this pedial one positive population and.
01:11:20FDA approved the use of
01:11:22alcoholism app and nap.
01:11:23Paclitaxel,
01:11:24irrespective of the line of therapy.
01:11:26But we do not have really.
01:11:29We really don't have data to
01:11:31know what would be the benefit
01:11:34beyond the first line treatment.
01:11:37So another study that was presented
01:11:40at ASCO 2020 used this time at
01:11:43PD one inhibitor called the
01:11:46pembrolizumab and combine it with
01:11:49different types of chemotherapy.
01:11:51There were three different regiments,
01:11:54not backlit axle.
01:11:57Paclitaxel and Jim Carbo and the patients
01:12:01were treated and field progression,
01:12:04toxicity or completion of
01:12:0635 cycles of treatment.
01:12:09And we did see Dan improvement in
01:12:12the progression free survival.
01:12:14That again was limited to those
01:12:17patients who overexpressed the PDL one.
01:12:19They used a different.
01:12:21Way of describing their positive
01:12:24iti's CPS score,
01:12:25which looks at the total percent
01:12:27of cells that are positive,
01:12:29including the tumour cells,
01:12:31lymphocytes and macrophages in the tumor.
01:12:34So this regimen is not FDA approved yet,
01:12:38but it is up for approval,
01:12:41and I think the message to take home
01:12:45from this study is that you can use
01:12:49different chemotherapy backbones,
01:12:51different chemotherapy regiments
01:12:53in combination with immunotherapy,
01:12:55and you can tailor the chemotherapy
01:12:58used based on the patients
01:13:00toxicities and prior treatments.
01:13:05So I'd like to say that there's the
01:13:08question why do certain patients stop
01:13:12responding to the immunotherapy?
01:13:15And there are mechanisms of resistance
01:13:18with activation of the Mac or AKT pathways,
01:13:22and Fortunately we do have.
01:13:26Hitters tyrosine kinases that could turn
01:13:29those pathways off and there are some
01:13:32early studies that basically combine them.
01:13:35Make inhibitor called cobimetinib.
01:13:37There is actually approved for
01:13:40treatment time of Melanoma with taxol.
01:13:43And that other look at is Alyssa Map.
01:13:46So basically the same regimen from the
01:13:49Impassion 130 trials and early results show
01:13:52an excellent control in the tumour burden,
01:13:56and very promising response rates.
01:13:59So the chemoimmunotherapy was brought
01:14:02to earlier phases of treatment in
01:14:06new agement setting for women who
01:14:10have triple negative breast cancer.
01:14:13And are treated with corrective
01:14:15intent before the surgery and there
01:14:18was a significant improvement in
01:14:20the rate of pathological complete
01:14:22response and event free survival
01:14:25without significant increase in the.
01:14:29Adverse events this regimen
01:14:33is not in the approved yet.
01:14:35Waiting additional data
01:14:37in the overall survival.
01:14:39So I tried to make the point that
01:14:43important breakthrough developments.
01:14:46And that we do have important
01:14:48breakthrough developments in the
01:14:50treatment of her two positive and
01:14:53triple negative breast cancer,
01:14:54the treatment has to be personalized based
01:14:57on the cancer subtypes and different
01:15:00molecular characteristics of the two more,
01:15:02but also looking at the
01:15:05patients comorbidities,
01:15:05prior treatments and patients preference and.
01:15:09Participation in clinical trials is very
01:15:11important to continue to improve the
01:15:14outcome of different types of breast cancer.
01:15:17I am very happy to say that we have
01:15:20an expanding large list of clinical
01:15:23trials for all subtypes and all
01:15:26stages of breast cancer at Yale.
01:15:29And we are all a team fighting for hope and
01:15:34also fighting for curing breast cancer.
01:15:38And these are some contact information
01:15:42if you choose to call us after
01:15:46this meeting is over.
01:15:48Thank you.
01:15:50Thank you so much Doctor Bulgar that was
01:15:53quite a Tour de force in the latest in
01:15:56uncut medical oncology and drug therapy.
01:15:58We actually don't have a ton of time
01:16:00but there were so many questions.
01:16:02I just love this panel and more
01:16:05importantly the attendees who really
01:16:07took so much time out of their evening
01:16:09to stay with us and listen to what
01:16:12smilow and our Cancer Center is doing.
01:16:14So this is almost like speed dating.
01:16:16I'm going to fire off some questions if.
01:16:20To our panelists and hopefully just keep
01:16:22those answers as quick as possible.
01:16:24But this is really all of our.
01:16:27Attendees really deserve answers
01:16:29to their questions,
01:16:31which I tried to do in the
01:16:34background couple for Doctor Moran.
01:16:36One is a question on angiosarcoma
01:16:39after treatment for a radiation
01:16:41therapy 10 years after mastectomy.
01:16:44This comes from an Peterson and from her mom
01:16:47who required a pretty extensive resection.
01:16:51What percentage of patients
01:16:53develop osteosarcomas,
01:16:54and is there a gene that can
01:16:57differentiate with that?
01:16:59And kind of moving along those
01:17:01lines is from those radiation
01:17:04damage the skin and tissue,
01:17:07thus making reconstruction different
01:17:08difficult after mastectomy.
01:17:10OK, so to answer the first question,
01:17:13yes, second malignancy in the
01:17:16radiation field can occur.
01:17:18It is pretty rare we quote the number
01:17:22of .01% at 10 years and I think
01:17:26you know that's probably accurate.
01:17:28At best I've seen maybe 2 in
01:17:31my 20 year career of a sarcoma
01:17:34that was radiation induced,
01:17:36so it's unfortunate there isn't
01:17:38any way for us to be able to
01:17:41identify those patients other than
01:17:43maybe possibly the ATM mutation,
01:17:45which isn't necessarily linked
01:17:47to sarcomas per se,
01:17:49but they do have significantly
01:17:51more toxicity from the radiation,
01:17:53and it could be that they have a
01:17:56higher incidence of 2nd malignancies
01:17:58related to the radiation.
01:18:00Other repair mechanisms are not
01:18:02as established as someone who
01:18:05doesn't carry that mutation.
01:18:07The second question,
01:18:09as far as reconstruction,
01:18:11that is a very,
01:18:13very excellent question and we
01:18:15deal with this all the time.
01:18:18Yes, radiation does cause the image,
01:18:21and for this reason,
01:18:23when you undergo a mastectomy and
01:18:26then get radiation and then have
01:18:29reconstruction in the delayed setting.
01:18:32Or what needs to happen is
01:18:34a couple of things.
01:18:35One is that you want to wait at
01:18:38least six months or so to allow the
01:18:40skin to completely heal 2 is that
01:18:43you want to have an experienced
01:18:45a plastic surgeon who knows.
01:18:48Has experienced with the radiation
01:18:50and how that tissue looks like Inter
01:18:54operatively and 3rd is that unless
01:18:56you've had an expander place you
01:18:59really can't do an implant based
01:19:01reconstruction and so for that
01:19:03reason most of those patients who
01:19:06have delayed reconstruction and
01:19:08haven't had an expander placed will
01:19:11have to have a autologous flap and
01:19:13what that means is just putting
01:19:16in tissue from somewhere else,
01:19:18whether it be their abdomen or
01:19:21their back or their butt so.
01:19:25Thank
01:19:25you, I'm kind of going back to an earlier
01:19:28and just more generalized question on.
01:19:31You know how confident can we be
01:19:33when you haven't really dense breast
01:19:35tissue on mammogram and ultrasound
01:19:37in terms of detection of cancer?
01:19:39And how can women self check
01:19:42outside of their annual mammogram?
01:19:45Especially when the some of the
01:19:47recommendations for self breast
01:19:48exam are no longer recommended.
01:19:50This is just open to any and
01:19:51all of our panelists.
01:19:58Bob, no.
01:20:00Sure. So in terms of the dense breast tissue,
01:20:04you know we know that you know that's common.
01:20:08Maybe half of women have breast density.
01:20:11It's categorized and defined, but we know
01:20:14that can decrease sensitivity for mammogram.
01:20:16We know younger women are more likely to have
01:20:19you know denser breast tissue, but older
01:20:22women have denser breast tissue as well,
01:20:24so we know there's some limited sensitivity.
01:20:27We still know that mammography is the
01:20:29one tool that's been shown to define and
01:20:32reduce mortality from breast cancer,
01:20:34so we still do use mammogram.
01:20:36I would say that these days and we're
01:20:38fortunate United States where pretty
01:20:40much all using digital mammogram.
01:20:42And most of us are also using Tomo synthesis,
01:20:45which gives us a little bit more
01:20:47sensitivity still in terms of getting
01:20:49more of a 3D picture of the breast and
01:20:52then just to comment on ultrasound,
01:20:54I usually tell my patients that
01:20:56ultrasound might pick up.
01:20:58Maybe 3 or 4, maybe 4% per thousand
01:21:00more more breast cancer,
01:21:02so it's something that you know.
01:21:04Some women choose is all this.
01:21:06No, that's in part political.
01:21:07But when you look at the medical
01:21:10aspect of it,
01:21:11it's an option for women with dense,
01:21:13dense breast tissue.
01:21:14And we know that MRI is out there
01:21:16and is used selectively in high
01:21:18risk populations like germline
01:21:19mutations or other populations.
01:21:21And we know that that could be considered
01:21:24the gold standard in terms of sensitivity.
01:21:28But we use it less for multiple reasons.
01:21:30That was the second part of that question,
01:21:33I'm sorry.
01:21:35In terms of self breast exams,
01:21:37thoughts on that? Yeah, you
01:21:40know the data. Hasn't shown us that
01:21:42that breast self exam you know improve,
01:21:45you know survival or as relates
01:21:47to breast cancer and and certainly
01:21:49some women still choose to do that
01:21:52and it's their right to do that.
01:21:54And I would say that if one is
01:21:56doing that maybe just being trained
01:21:58to do it most effectively but we
01:22:01don't have necessarily other tools,
01:22:03But that's not something that we.
01:22:06Generally recommend those.
01:22:07Certainly someone certainly
01:22:08choose to do that.
01:22:11That that we cannot really rely on the
01:22:14breast exam to detect the breast cancer,
01:22:17and that's the value of the screening
01:22:20mammogram to detect them way before
01:22:23the breast cancers become palpable.
01:22:25American Cancer Society discourages self
01:22:27breast exam as routine detection method,
01:22:30but enciende guidelines do include a
01:22:33recommendation for what we call breast
01:22:36awareness because it is very important for
01:22:39women to know how their breast feel like.
01:22:43It also for premenopausal women the best
01:22:45time to check would be under 10 days
01:22:47after the onset of the menstrual periods,
01:22:50when there are less hormonal changes
01:22:52in the breast and we do know that 10 to
01:22:5615% of the breast cancers are diagnosed
01:22:58because women do find a lump in the breast.
01:23:01So I think that while never say I'm
01:23:04just going to rely on the breast exam,
01:23:07go for the screening mammogram.
01:23:08I do encourage my patients to have
01:23:11a breast awareness and be aware of.
01:23:13How their breast tissue feels like.
01:23:15Yeah, I agree with that as well,
01:23:18and I also tell patients for anyone
01:23:20that's had radiation as they
01:23:22are finishing their radiation.
01:23:24I tell them that during the first
01:23:26six months post radiation that they
01:23:28should actually do a breast exam,
01:23:30not to be alarmed,
01:23:31but that all the changes that
01:23:33they're feeling is the scar
01:23:35tissue that's developing.
01:23:37Because with radiation you develop
01:23:38scar tissue just like you do with surgery,
01:23:41and it's just an opportunity for them
01:23:43to learn what their new breast feels like,
01:23:46so that down the road.
01:23:48They're not alarmed if they
01:23:50suddenly check their breasts at
01:23:52one year and and suddenly feel
01:23:54lumps and bumps because the vast
01:23:56majority of them are normal.
01:23:59And this is for two things from Caitlin.
01:24:02One is, she said, please do self checks
01:24:06and that's how she found her cancer again.
01:24:09Absolutely, if a woman feels comfortable
01:24:12with their own breast exams and
01:24:15seeing any changes of noticing them,
01:24:17I 100% supportive of doing self breast exams.
01:24:21She also had a really
01:24:24thoughtful question about.
01:24:26Stage 2A triple positive breast
01:24:27cancer with no lymph nodes.
01:24:29What are the thoughts on neural
01:24:31links and also thoughts on who?
01:24:33For ectomy on a 36 year old female on
01:24:36tamoxifen for the above mentioned diagnosis.
01:24:42Want me to comment on that?
01:24:45The you know neural links that you know,
01:24:47I believe you referring to Noor
01:24:49Atnip which is an oral sort of pan.
01:24:52Her two tyrosine kinase inhibitor.
01:24:54And that was studied, and it seemed to be.
01:24:59More effective,
01:25:00perhaps in the ER positive group,
01:25:02I believe that was the EXANET trial.
01:25:06It's oral, I think it was taken for a year.
01:25:10Has some pretty significant side effects
01:25:12in terms of especially diarrhea,
01:25:13but there's ways to sort of try to
01:25:16preempt that prophylaxis against it.
01:25:18I believe that trial also did include.
01:25:23Women who had new regiment therapy and there
01:25:26was a similar trend in terms of benefit.
01:25:29Interesting thing these to my not to
01:25:31my as I recall is that in that trial
01:25:34women hadn't seen Pertuzumab which is
01:25:37now sort of a standard complemented
01:25:39as Doctor Boger was showing.
01:25:41As earlier with Herceptin which
01:25:42is also called trust.
01:25:44Choose a map in these sort of neoadjuvant
01:25:46and then sometimes following into the
01:25:49advanced setting so there is some data there,
01:25:52but there's not really data.
01:25:53Looking at that agent.
01:25:55In the setting of prior
01:25:57exposure to produce in abduls.
01:25:58To my knowledge,
01:26:00in addition to trust him then.
01:26:03And then the second part,
01:26:04Doctor Bulgaro,
01:26:04did you want to comment on the second bar?
01:26:07Sure, so the IT is well established
01:26:10based on the large softex trial that
01:26:13young women do benefit from ovarian
01:26:16suppression. That is done with.
01:26:22With drugs like Zola decks or can
01:26:25settle in and in addition to oral
01:26:29anti hormonal treatment, now the.
01:26:33Removal of, I mean that basically puts
01:26:35the patients into a chemical menopause.
01:26:38There is the option of a surgical menopause,
01:26:41particularly if there is a genetic
01:26:43predisposition for ovarian cancer,
01:26:45but that is an irreversible option, you know.
01:26:47So I think that it has to be discussed
01:26:50with your treating physician,
01:26:52the pros and cons of prophylactic
01:26:55bulfer ectomy.
01:26:55If there is a cancer predisposition,
01:26:58genes that would increase the risk
01:27:00for ovarian cancer and someone is.
01:27:02Delete sure that is done conceiving.
01:27:07Then, prophylactically for Ectomy
01:27:09is an option but otherwise
01:27:12ovarian suppression with this.
01:27:15Every three months injections is the
01:27:17standard of care in addition to oral,
01:27:19anti estrogen therapy and then
01:27:20you have the tamoxifen or even
01:27:22better than automatic inhibitor.
01:27:27So much first of all to our
01:27:29panelists around of applause.
01:27:31Although we won't be able to hear
01:27:34it from her doctor Bulgarella
01:27:36Garian Moran for you know, really.
01:27:393 state of the art fantastic talks.
01:27:42And here at Yale and the Smilow
01:27:44Cancer Center at Water for Dell,
01:27:47NM westerly, it was a great evening.
01:27:50And really more importantly to
01:27:52our attendees or cancer survivors,
01:27:54those are going through this right now.
01:27:58Your questions were super thoughtful.
01:28:00I tried to answer some of them
01:28:02while our panelists were giving
01:28:04their giving their talks.
01:28:05This has been recorded and
01:28:07you can go back to it.
01:28:09And of course,
01:28:10we're always here for you and
01:28:12happy to answer any questions.
01:28:17Thank you so much for a wonderful
01:28:19evening and stay healthy.
01:28:21Take care guys, thank you.
01:28:22Thank you, thank you.