"Breast Cancer in Young Women: Optimizing Knowledge and Care to Improve Outcomes"

Transcript

• 00:00Gives me,
• 00:02exceptional joy to be able
• 00:04to introduce,
• 00:05Anne Partridge.
• 00:08Anne,
• 00:10and I have known each
• 00:11other a long time,
• 00:13And I won't say exactly
• 00:15how long, but
• 00:17since she was a second
• 00:19year fellow,
• 00:20we've known one another and
• 00:22worked together very closely
• 00:25at, Dana Farber for years
• 00:27and years and years.
• 00:30And she is still the
• 00:31person who I speak to
• 00:32most regularly at Dana Farber,
• 00:35which used to be once
• 00:37a week, but is now
• 00:39a little less as she's
• 00:40become even more busy.
• 00:44So Anne is a health
• 00:45services researcher,
• 00:47has focused on
• 00:49the care
• 00:50of
• 00:51young women with breast cancer,
• 00:54on survivorship,
• 00:56on a whole range of
• 00:57other issues. One of the
• 00:59first things we ever did
• 01:00together was look at
• 01:02giving results back to clinical
• 01:04trial participants
• 01:06and had a whole series
• 01:07of papers
• 01:08back.
• 01:09Oh my god, in the,
• 01:11early two thousands about that
• 01:14particular topic.
• 01:17Anne is the interim chair
• 01:19of medical oncology at Dana
• 01:21Farber and has been for
• 01:22the past couple of months.
• 01:25She
• 01:26is on the ASCO board,
• 01:29is the
• 01:30one of two chief scientific
• 01:32advisers
• 01:33for Komen,
• 01:35and is the cochair of
• 01:37the Alliance Breast Committee among
• 01:39other things. And I just
• 01:40calculated up that she has,
• 01:41like, two hundred percent effort.
• 01:44She also is perhaps the
• 01:47only person in the world
• 01:48who could tolerate something that
• 01:50I find very embarrassing, and
• 01:52she doesn't somehow,
• 01:54which is that she actually
• 01:56occupies the Eric p Weiner
• 01:58chair in breast cancer research
• 01:59at Dana Farber,
• 02:01which is an an an
• 02:02embarrassment
• 02:03to me
• 02:04that my name is on
• 02:05such a thing. But,
• 02:07again,
• 02:08Anne is perhaps my only
• 02:10friend who could
• 02:12or colleague who could ever
• 02:13tolerate being in that, particular,
• 02:17chair.
• 02:18So, Anne, it is a
• 02:20true pleasure having you here
• 02:22today.
• 02:23I know everyone you've met
• 02:24with has had a really
• 02:26wonderful time meeting with you,
• 02:28and,
• 02:29we look forward to your
• 02:30talk, Breast Cancer in Young
• 02:32Women, Optimizing Knowledge and Care
• 02:34to Improve Outcomes. Oh, and
• 02:35before you start talking, I'm
• 02:37gonna present you
• 02:39with the,
• 02:41Yale Cancer Center Grand Rounds
• 02:43Patricia
• 02:44Kingsbury lecture.
• 02:46Why?
• 03:03Alright. So it is it
• 03:04is really a joy to
• 03:06be here today and no.
• 03:09And,
• 03:10to talk with all of
• 03:11you about this.
• 03:12I, as you heard from
• 03:14Eric, I I feel very
• 03:15at home here since, many
• 03:18since Eric's here and and
• 03:19many of my former colleagues.
• 03:20And, of course, I've
• 03:22gotten to know many people
• 03:24who were either here or
• 03:25elsewhere before here
• 03:26over the years and and
• 03:28had many wonderful collaborations
• 03:30and that continue on to
• 03:31today.
• 03:32I'm gonna focus on, kind
• 03:34of the thing that I
• 03:35eventually landed on
• 03:38during my career to focus,
• 03:40the my, you know, kind
• 03:41of
• 03:42research and clinical efforts
• 03:44such that I could try
• 03:45to, you know, make a
• 03:46little dent in the world.
• 03:48And as you heard, I
• 03:49I've known Eric a long
• 03:50time.
• 03:51And, you know, one of
• 03:52the reasons that,
• 03:54beyond the teams that we've
• 03:55built, that we've started to
• 03:57make a little dent in
• 03:58the world is because I
• 03:59was in a place with
• 04:00a mentorship that was just
• 04:01so supportive
• 04:03of of the kind of
• 04:04work that I'm gonna talk
• 04:05about. So I'm I'm really
• 04:06forever grateful of that.
• 04:09So let's start with some
• 04:10basic facts around
• 04:13we're gonna talk about breast
• 04:14cancer in young women, but
• 04:15how how do we get
• 04:16there? Well, first, I think
• 04:17there needs to be a
• 04:18recognition
• 04:20that, fortunately,
• 04:21at least as of twenty
• 04:22twenty four, while we still
• 04:24have far to go,
• 04:26the
• 04:27now about, you know, just
• 04:28over a majority of people
• 04:30diagnosed with cancer
• 04:32will
• 04:33be long term survivors.
• 04:35So we are getting better
• 04:37and better at both diagnosing
• 04:39early, and you could even
• 04:40argue some some diseases overdiagnosing
• 04:43and treating, in particular, around
• 04:45breast cancer,
• 04:47our cancers and creating survivors,
• 04:50which is a, you know,
• 04:51good problem to have. We
• 04:52wanted more and more survivors,
• 04:54and I just had the
• 04:55the, joy of meeting with
• 04:56Tara Santa and her crew
• 04:58about the survivorship work you've
• 04:59got going on here, which
• 05:00is terrific.
• 05:01And breast is one of
• 05:03the biggest groups as you
• 05:04can see, and we all
• 05:05know this clinically
• 05:06of survivors,
• 05:09because, you know, most women
• 05:10and some men will will
• 05:12develop breast cancer, but those
• 05:13who develop breast cancer
• 05:15will be long term survivors,
• 05:17even, you know, moving more
• 05:18towards long term survivors with
• 05:20metastatic disease, thanks to many
• 05:22of the breakthroughs. So when
• 05:23I speak about survivorship, I'm
• 05:24speaking about kind of the
• 05:26global survivorship
• 05:27of for many
• 05:29issues. But particularly with young
• 05:30women, even with metastatic disease,
• 05:33we're now seeing different subtypes
• 05:34living out, you know, five,
• 05:36ten, fifteen years and beyond
• 05:38more so than we did
• 05:40previously. So we need to
• 05:41make sure we incorporate them
• 05:42as well because they're not
• 05:44dying of other things, fortunately.
• 05:46And yet when we think
• 05:48about young women, and this
• 05:49is one of the things
• 05:49that kind of really got
• 05:51me paying attention when I
• 05:52was that second year fellow
• 05:54working in Eric's clinic, is
• 05:55that, you know, even though
• 05:57the majority will be survivors,
• 05:59you can see the y
• 06:00axis on this curve on
• 06:01the on that's in the
• 06:02center of the slide.
• 06:04It starts at zero and
• 06:05goes up to ten to
• 06:06fifteen percent.
• 06:07The youngest women actually had
• 06:09the highest risk of recurrence
• 06:11and mortality
• 06:12from breast
• 06:13cancer. Theirs had similar,
• 06:16cancer specific death rates as
• 06:18the oldest women. And these
• 06:20are recent data where we've
• 06:21now incorporated,
• 06:23you know, HER2
• 06:25positivity or negativity
• 06:27into our national dataset.
• 06:29And there's a five percent
• 06:31difference
• 06:32where the oldest and the
• 06:33youngest
• 06:34have the worst mortality outcomes,
• 06:38in breast cancer.
• 06:39And so, you know, what's
• 06:40going on there and what
• 06:41can we do to mitigate
• 06:42that has been something that
• 06:44that many of us have
• 06:45focused on.
• 06:46We also know, and these
• 06:48are some of the latest
• 06:49data
• 06:50from the CANTO cohort, which
• 06:51is a prospective cohort of
• 06:54of cancer survivors now breast
• 06:56and, I think, lung cancer
• 06:57in France, population essentially population
• 07:00based. It's in many, hospitals
• 07:02in France.
• 07:03And we know that young
• 07:04age
• 07:05of breast cancer is also
• 07:06associated with a worsening quality
• 07:09of life trajectory. You can
• 07:10see that as ones in
• 07:11the red, whether they either
• 07:12start bad, but especially those
• 07:14that started out kind of
• 07:15okay and then come down.
• 07:17The clinical characteristics
• 07:19associated with being part of
• 07:20that trajectory
• 07:21include being younger
• 07:23and other things that are
• 07:24related to being younger. And
• 07:26so not only are young
• 07:27women stuck with the risk
• 07:29of, you know, higher risk
• 07:30of recurrence
• 07:31and warranting more treatment, but
• 07:33they're also
• 07:34in part related to that,
• 07:36have a worse psychosocial
• 07:37trajectory
• 07:39after their diagnosis and well
• 07:40into survivorship
• 07:41that's been well documented.
• 07:43So I I think, you
• 07:45know, hopefully, I've just shown
• 07:46you that breast cancer and
• 07:47anybody who cares for these
• 07:48patients and our young patients
• 07:49is just more complicated.
• 07:51This is true of pretty
• 07:52much all of the AYA
• 07:53cancers.
• 07:55And and one of the
• 07:56reasons that it's complicated is
• 07:57because they're not only dealing
• 07:58with the decisions around
• 08:00chemotherapy, endocrine therapy, local therapy
• 08:02that you can see on
• 08:03the top of this slide,
• 08:04which are, you know, hard
• 08:06decisions when they are decisions
• 08:08and made even harder sometimes
• 08:10by where young people are
• 08:11in their lives,
• 08:13and especially if they have
• 08:14more aggressive disease, which warrant
• 08:15more of these things often.
• 08:17But they suffer from making
• 08:19the decisions around everything else
• 08:20you see around that diagram,
• 08:22you know,
• 08:23not the least of which
• 08:24is fertility and the idea
• 08:26of premature menopause,
• 08:28the role functioning at a
• 08:29time in one's life when
• 08:30they're earlier either in their
• 08:32partnership, their careers, or may
• 08:35not be done with school,
• 08:37sexual health and body image,
• 08:38something that's not unique to
• 08:40young onset cancers, but is
• 08:42certainly accentuated
• 08:44by being young. And then
• 08:45the genetics of young onset
• 08:47cancers plays in, of course,
• 08:49in,
• 08:50more so for younger patients.
• 08:51And that all contributes to
• 08:53their psychosocial health and functioning,
• 08:56which can when one of
• 08:57the reasons we see,
• 08:58things going south for our
• 09:00youngest patients and therefore, perhaps
• 09:02need to be focusing more
• 09:03on them as I know
• 09:03you guys are doing too.
• 09:06So now a few years
• 09:07ago, a group of us
• 09:09got together with the Young
• 09:10Survival Coalition, an advocacy group
• 09:12based in New York but
• 09:13international
• 09:14that focuses on young onset
• 09:16breast cancer and said, okay.
• 09:18What are our research priorities?
• 09:20What do we really wanna
• 09:21focus on recognizing we can't
• 09:22focus on everything?
• 09:24And the group came up
• 09:25with, you know, a pretty
• 09:26overarching,
• 09:28broad set of priorities,
• 09:30and you can see them
• 09:31listed here. I'm gonna focus
• 09:32on a few recent data
• 09:34around treatment,
• 09:35fertility, and then the overarching
• 09:37quality of life and survivorship,
• 09:39now. But I I do
• 09:41think this that that piece
• 09:42is nice if anybody's focusing
• 09:44on AYA's because it does
• 09:45get at the things that
• 09:46we heard from our the
• 09:47patients and advocates,
• 09:49what's important to them, and
• 09:50it and, obviously, it was
• 09:51consistent with what was important
• 09:53to the the,
• 09:55the,
• 09:56researchers in the room as
• 09:57well.
• 09:58One of the things that
• 09:59we also did at Dana
• 10:00Farber now
• 10:02almost twenty years ago
• 10:04was to recognize
• 10:05that
• 10:06there were not great datasets
• 10:09for our youngest patients with
• 10:10either enough young patients. So
• 10:12clinical trials are very well
• 10:14annotated.
• 10:16Big cohorts very well annotated
• 10:18like nurses health study and
• 10:19women women's health initiative.
• 10:21But the young women who
• 10:22go on to get breast
• 10:23cancer in the clinical trials,
• 10:25just the proportion of young
• 10:26women, even though they participate
• 10:28in trials as much if
• 10:29not more than anybody else,
• 10:30the absolute numbers
• 10:32are fairly small.
• 10:34And so there were very
• 10:35few place. And, you know,
• 10:36if you look at SEER
• 10:36data, it's great for big
• 10:38thirty thousand foot views, but
• 10:39very little granularity, especially when
• 10:41we first started looking into
• 10:42the issues very early as
• 10:43a young woman. And so
• 10:45we realized that we just
• 10:46didn't have a place to
• 10:47get many of the answers
• 10:48that we needed. And so,
• 10:50fortunately, again, I was supported,
• 10:52in large part by Eric
• 10:54and others at Dana Farber
• 10:56to create a cohort,
• 10:57to look at our young
• 10:58patients over time. And we
• 11:00called it, the helping ourselves,
• 11:02helping others
• 11:04study, which, of course, at
• 11:05Christmas is ho ho, which,
• 11:07you know, it's a little
• 11:08bit regretful.
• 11:09But it was with the
• 11:10idea that I think I
• 11:12was young at the time
• 11:13and thought that, you know,
• 11:14maybe I was gonna get
• 11:14breast cancer soon. It's one
• 11:16good thing to age out
• 11:17of that. And young the
• 11:18Young Women's Breast Cancer Study
• 11:20is something that we've now
• 11:21been running for almost twenty
• 11:22years,
• 11:23and it's a prospective cohort
• 11:25that, we said every woman
• 11:27forty and under at twelve
• 11:28hospitals
• 11:30in mostly Eastern Massachusetts, but
• 11:32we also, roped in folks
• 11:33in Colorado and Minnesota
• 11:36and in Toronto.
• 11:38And we've been following them,
• 11:40and we collected a lot
• 11:41of data over time, and
• 11:42we're still doing it. So
• 11:44focusing on disease and tumor
• 11:45biology and molecular characteristics,
• 11:48and then ranging to the
• 11:49things that I typically would
• 11:50study more like psychosocial behavior
• 11:52on survivorship issues. And we
• 11:54enrolled,
• 11:55about thirteen hundred patients. At
• 11:58one point, I remember having
• 11:58a conversation with Eric and
• 12:01saying, okay. You have so
• 12:02much data. Maybe it's time
• 12:03to stop enrolling. And I
• 12:04said, you know what? I
• 12:05think that's the right answer
• 12:07and start really just delivering
• 12:08on what we have.
• 12:10And we had really high
• 12:11response rates from patients. We've
• 12:13collected surveys
• 12:15over time. We have very
• 12:16nice accrual to our biobank
• 12:17too, which is, of course,
• 12:18linked to the annotated data
• 12:21data. And we've begun to
• 12:23really,
• 12:23capitalize on this resource. The
• 12:26median follow-up is about eleven
• 12:27years at this point. It's
• 12:29probably about twelve now. And
• 12:30so if anybody has any
• 12:31good ideas, be please do
• 12:33be in touch because the
• 12:34goal is not to just
• 12:35look at it with the
• 12:35people that are working on
• 12:36it right now, but to
• 12:37really open it up so
• 12:38people can ask questions or,
• 12:40you know, put cohorts together
• 12:42with with other people's datasets.
• 12:44And so we've we've published
• 12:46a lot on this, and
• 12:47some of the work I'll
• 12:48show you in the next
• 12:49few minutes, focuses on,
• 12:51analyses done. And one of
• 12:53the issues
• 12:54that,
• 12:55I know is near and
• 12:56dear to folks here in
• 12:57the room that has come
• 12:58up over and over and
• 12:59over again is local therapy
• 13:01decisions for our young patients.
• 13:04Now the literature would tell
• 13:05us that young patients have
• 13:06a higher risk
• 13:08of local recurrence,
• 13:10but survival is the same.
• 13:11And that's true especially when
• 13:13you look at tumor subtypes.
• 13:15And so
• 13:17age should not be a
• 13:18contraindication
• 13:19to breast preservation. That's kind
• 13:21of the mantra. There's data
• 13:22to support that. I still
• 13:23get phone calls from my
• 13:25radiation oncologist. This person's only
• 13:26twenty two. How much data
• 13:28are there for a twenty
• 13:29two year old? And
• 13:32I say, you're right. But,
• 13:32you know, we don't just
• 13:32because we don't have data
• 13:33doesn't mean that there's a
• 13:35contraindication.
• 13:35We gotta continue to grow
• 13:37that. And so we we
• 13:38try and treat our patients
• 13:39this way, but we are
• 13:40trying to learn from this.
• 13:42And yet knowing
• 13:44the issues around equal survivor
• 13:46survival,
• 13:48we still have seen this
• 13:49trend, which is still I
• 13:51think it's plateauing a little
• 13:52bit now. We heard some
• 13:54discussions about this earlier with
• 13:55some of your
• 13:57some of your surgical fellows
• 13:58who are doing health services
• 13:59research,
• 14:00that, you know, young women
• 14:02still go on not only
• 14:03to choose mastectomy, but bilateral
• 14:05mastectomy not infrequently
• 14:07even when they don't have
• 14:08a known hereditary predisposition to
• 14:10breast cancer or any other
• 14:12obvious,
• 14:13family or personal,
• 14:15history.
• 14:16So, you know, what's going
• 14:17on here? And is this
• 14:18contributing
• 14:19to better health in the
• 14:21long run, or is this
• 14:22contributing to more psychosocial issues,
• 14:24or are they responding to
• 14:26something and fixing a problem
• 14:28with the wrong solution or
• 14:30the right solution for them?
• 14:31We don't know, but many
• 14:32people are looking into this.
• 14:33These are just data to
• 14:34show that, you know, having
• 14:36a contralateral prophylactic
• 14:38mastectomy is not a panacea
• 14:40to all that ails a
• 14:41person, even though sometimes that's
• 14:43the way I think some
• 14:44women feel. It's in their
• 14:45fight or flight reaction to
• 14:46a new onset breast cancer.
• 14:48And you can see here
• 14:49the very high rates
• 14:51of patients,
• 14:53that have, you know, in
• 14:54you know, self consciousness, feeling
• 14:55less physically attractive,
• 14:57dissatisfied with appearance, less feminine.
• 14:59I mean, you and those
• 15:00percentages are at fifty to
• 15:02sixty percent less sexually attractive,
• 15:04even avoiding people in a
• 15:05substantial minority, body less whole,
• 15:07dissatisfied, dissatisfied with scars. So,
• 15:10you know, when there are
• 15:11rigorous looks at how people
• 15:13are feeling, there's a lot
• 15:14of, you know, scars, both
• 15:16physically and emotionally from extensive
• 15:19surgery. And so trying to
• 15:20understand
• 15:21when we know there's no
• 15:22clear survival advantage, what's what's
• 15:23going on and making sure
• 15:25people are making kind of
• 15:26value based decisions that aren't
• 15:28being driven by emotions of
• 15:30the moment in fight or
• 15:31flight, but are driven by,
• 15:33kind of a calmness and
• 15:35an ability to weigh the
• 15:36pros and cons, I think,
• 15:37is what many of us
• 15:38are working on.
• 15:39And one of the things
• 15:40that one of my, postdocs
• 15:42looked at recently was, well,
• 15:43what are the data for
• 15:44these young patients
• 15:46when they don't have a
• 15:47known hereditary predisposition to breast
• 15:49cancer,
• 15:51for a second primary? And
• 15:53she looked in the young
• 15:53woman's cohort.
• 15:55And you can see here
• 15:56we were able to identify
• 15:58almost seven hundred patients who
• 15:59hadn't had bilateral mastectomy,
• 16:02and were, you know, still
• 16:04in active follow-up.
• 16:06Obviously, some of them had
• 16:07competing
• 16:08events like recurrence or metastases,
• 16:11and some of them had,
• 16:12nonbreast cancer,
• 16:14nonbreast cancer deaths.
• 16:17Sorry. Recurrence is probably not
• 16:18the right word word there
• 16:19because we're looking at oh,
• 16:20recurrence,
• 16:22elsewhere and recurrence. I think
• 16:23it's local recurrence. And we
• 16:24were looking at second non
• 16:26breast primaries.
• 16:28And you can see here
• 16:29that
• 16:31this group was representative
• 16:34once you took the people
• 16:34who had bilateral mastectomies away.
• 16:37So there were relatively
• 16:39small proportions
• 16:40of mutation carriers. You can
• 16:41see only about six percent
• 16:43even though the rate of
• 16:44mutation carriers in our cohort
• 16:46is more like, you know,
• 16:48for just BRCA one and
• 16:49two, it's about fifteen percent.
• 16:50And if you include kind
• 16:52of those nine eight or
• 16:53nine additional genes, it goes
• 16:55up to about twenty five
• 16:56percent,
• 16:57because it is you know,
• 16:58the prevalence is fairly high
• 17:00if you look at our
• 17:00very young patients.
• 17:02And otherwise, there were no
• 17:04other you know, it was
• 17:04an interesting cohort,
• 17:06but, I think the most
• 17:07important thing is that still
• 17:09within this group, fifty percent
• 17:10said they had a family
• 17:11history of breast or ovarian
• 17:13cancer once you removed the
• 17:14people who didn't have bilateral
• 17:15mastectomies.
• 17:17And here's what we saw.
• 17:19The cumulative incidence of a
• 17:20second primary breast cancer at
• 17:23ten years
• 17:24among almost seven hundred women
• 17:26was pretty low. It was
• 17:27like two point three percent
• 17:29at ten years, one point
• 17:31four percent.
• 17:32So this is removing the
• 17:33higher risk people, which most
• 17:34of our population based data
• 17:36don't have an understanding of
• 17:38that ten percent who are
• 17:39more likely to get breast
• 17:40cancer or new primary over
• 17:42the next ten to twenty
• 17:43years.
• 17:44We dug a little deeper
• 17:45and looked at those who
• 17:47did have a known hereditary
• 17:48predisposition who'd kept their breast
• 17:50at six percent. And you
• 17:52can see here that it
• 17:53was five and a half
• 17:54times higher among those patients
• 17:56who had germline
• 17:57pathogenic variants. Not surprising. So
• 18:00they had a nine point
• 18:01one percent rate compared to
• 18:03a one point seven percent
• 18:05rate when you took them
• 18:06away. So even lower at
• 18:08ten years,
• 18:10which is,
• 18:11I think, very reassuring for
• 18:13our young survivors.
• 18:15Interestingly,
• 18:16when we looked at other
• 18:18differences, this was the only
• 18:20other major factor that stood
• 18:21out. Patients who had DCIS
• 18:25had a higher risk of
• 18:27a second primary
• 18:29than patients who had presented
• 18:31with an invasive breast cancer.
• 18:32Now my immediately thinking was,
• 18:34okay. The vast majority of
• 18:35these people have trip have
• 18:36hormone receptor positive breast cancer.
• 18:38Our young patients don't wanna
• 18:40take the hormones just like
• 18:41our older patients don't for
• 18:42DCIS. It's kinda optional for
• 18:44DCIS.
• 18:45Maybe that because there's no
• 18:46clear survival advantage. So maybe
• 18:48that's why we're seeing the
• 18:50difference.
• 18:50And we did look at
• 18:51this in a subset analysis.
• 18:53The numbers get super small.
• 18:55There are only fifteen events,
• 18:57but it wasn't a clear
• 18:58explanation.
• 18:59So more work to be
• 19:00done. It may still be
• 19:01the hormonal differences, but it
• 19:03at least in our cohort,
• 19:04it wasn't obvious
• 19:06that it was just because
• 19:07of a lack of use
• 19:08of endocrine therapy in the
• 19:09patients with DCIS compared to
• 19:11the patients with invasive cancer.
• 19:12So something to keep an
• 19:13eye on
• 19:14and just think about whether
• 19:15or not if a young
• 19:16person's diagnosed with DCIS,
• 19:18then it may make more
• 19:20sense to do something bilateral
• 19:21because, you know, they don't
• 19:23have a competing risk typically
• 19:24of a systemic recurrence,
• 19:26ironically, even though it feels
• 19:28like a lot for a
• 19:29noninvasive cancer. We could discuss
• 19:31this later, Rachel. How do
• 19:32you feel about this?
• 19:34Alright. So so, you know,
• 19:37when we think about doing
• 19:38contralateral
• 19:40mastectomy then, I think when
• 19:41we support our young patients,
• 19:43we all try and present
• 19:44the pros and the cons
• 19:45in a kind of a
• 19:46nonjudgmental
• 19:47way. And our now our
• 19:48surgeons focus on this a
• 19:49lot. The other huge component
• 19:52to this when you think
• 19:53about pros and cons is,
• 19:55will they get peace of
• 19:56mind with this? And I
• 19:58know you have work going
• 19:59on here looking into this,
• 20:01and I'm thrilled that I'm
• 20:02part of,
• 20:04Rachel Greenup and Shoshana Rosenberg's,
• 20:07work called Consider,
• 20:09which you guys have open
• 20:10here too,
• 20:11which is a pragmatic
• 20:13implementation. It's a hybrid design
• 20:15effectiveness and implementation
• 20:17study
• 20:18where we are putting
• 20:20a, decision support tool into
• 20:23effect,
• 20:24over time at,
• 20:27four sites in North America.
• 20:29Where are the sites, Rachel?
• 20:29It's us, it's you, Duke,
• 20:32and Cornell.
• 20:33Right? And so over time,
• 20:35hopefully, we will be able
• 20:36to help our young patients
• 20:38in particular. And this is
• 20:39built out of Rachel and
• 20:41and,
• 20:42Shoshana's k award work to
• 20:44try and support patients better
• 20:46in the moment to make
• 20:48good decisions for themselves
• 20:49around the issue of how
• 20:51much breast surgery do I
• 20:52need,
• 20:53and does it make sense
• 20:54to take off the other
• 20:55side and and do preventative
• 20:57work.
• 20:58So very exciting and and
• 20:59nice to see this kind
• 21:00of coming from the data
• 21:02from the patients all the
• 21:03way through to an intervention
• 21:05that's actually in our clinics
• 21:07pretty soon. Pretty soon.
• 21:09So very exciting.
• 21:11Now getting back to that
• 21:12graph that I showed you
• 21:13where our youngest patients who
• 21:14were in red were doing
• 21:16as poorly as our oldest
• 21:17patients who have different reasons
• 21:19for their disparities,
• 21:20now we're separating the that
• 21:22graph by the,
• 21:24canonical
• 21:26breast cancer subtypes. So we've
• 21:27got hormone receptor positive,
• 21:30lower grade, which is a
• 21:31surrogate for luminal a subtype
• 21:33up on the left,
• 21:35HER2 positive on the bottom
• 21:37left, and then you've got
• 21:38the high grade hormone receptor
• 21:40positive, HER2 positive, or HER2
• 21:43negative,
• 21:44and then on the bottom
• 21:45right, triple negative. And you
• 21:46can see
• 21:47that where's the biggest
• 21:51deficit? Where's the biggest,
• 21:53disparity? It's actually
• 21:55in the group of patients
• 21:57that we think of as
• 21:59kind of the easiest to
• 22:01treat with early stage breast
• 22:02cancer, those with the the
• 22:04lower risk
• 22:05in theory, low grade or
• 22:07intermediate grade,
• 22:09hormone receptor positive disease.
• 22:11And that kinda makes sense.
• 22:13Right? Whenever you have a
• 22:14treatment
• 22:16that is effective,
• 22:18you see disparities in any
• 22:20population.
• 22:22Right? Because you can't it's
• 22:24harder to see
• 22:25disparities in a population when
• 22:27you don't have effective treatment.
• 22:28Disparities typically come out, especially
• 22:30when they're related to access
• 22:32or uptake of therapies,
• 22:35often in where you have
• 22:36effective therapy.
• 22:38And yet we also think
• 22:39there may be some biologic
• 22:40differences in our youngest patients
• 22:42who get these kind of
• 22:44wimpier
• 22:45looking
• 22:45tumors.
• 22:47So what are the data
• 22:49for that? So our group
• 22:50and others, and I'm showing
• 22:51you the data from the
• 22:52text in the SOFT trial
• 22:53that were published
• 22:55a year or so ago,
• 22:56that younger women are developed
• 22:59more luminal b than luminal
• 23:01a tumors you can see
• 23:02here. So, you know, in
• 23:04the in the bright blue
• 23:05or the turquoise is the
• 23:07luminal b's and the youngest
• 23:09proportionally greater. And then you
• 23:10see the kind of flip
• 23:11of that when you get
• 23:12to over forty, still young,
• 23:14but not under forty.
• 23:16And then when the group
• 23:17delved into more of the
• 23:18genomics, they saw more
• 23:20HRD,
• 23:21more copy number alteration
• 23:23in the younger patients. And
• 23:25our groups looked at this
• 23:26and also seen some differences
• 23:27in more specific genomic changes
• 23:30as well.
• 23:31And then when we looked
• 23:32at the luminal a and
• 23:33luminal b in text and
• 23:35soft,
• 23:36they're even among those two
• 23:38different subsets,
• 23:39the youngest patients seem to
• 23:41do worse
• 23:43in terms of their disease
• 23:44free survival.
• 23:46So some of this may
• 23:48be about
• 23:49size of tumors still and
• 23:51uptake of care, but there
• 23:52may also be something going
• 23:53on biologically. And we we
• 23:55just don't know all the
• 23:56answers. But
• 23:57but one would think then
• 23:59when you see these lower
• 24:00risk cancers
• 24:01and then you see that
• 24:02a younger person
• 24:03has a higher risk, well,
• 24:05maybe we should just give
• 24:06them all the tools we
• 24:07have. Right? Because they're at
• 24:09risk, and we don't wanna
• 24:10leave any kind of risk
• 24:11reduction on the table.
• 24:13And, unfortunately,
• 24:15our current data
• 24:17do lean towards that. These
• 24:19are the data from kind
• 24:21of the the hallmark genomic
• 24:23testing studies that have been
• 24:24done over the last decade,
• 24:26the TAILORx trial, the MIND
• 24:28ACT study and responder,
• 24:31you know, whether or not
• 24:32person had node positive or
• 24:34node negative breast cancer,
• 24:36chemotherapy.
• 24:37And these were studies with
• 24:39genomic testing and people in
• 24:41a lower moderate risk group
• 24:43randomized to chemo or no
• 24:45chemo, just for simplicity.
• 24:47And this these studies have
• 24:49spared many, many postmenopausal
• 24:51women
• 24:51from getting
• 24:53chemotherapy because
• 24:54all of them showed that
• 24:55among postmenopausal
• 24:57women with ER positive breast
• 24:58cancer
• 24:59where they had low to
• 25:01intermediate oncotype
• 25:02or,
• 25:03mammoprint scores,
• 25:04whether it was node negative
• 25:06or node positive when you
• 25:07think of responder,
• 25:08that chemotherapy
• 25:10did not add value.
• 25:12But, unfortunately, in premenopausal
• 25:14women,
• 25:15somehow, there is clear value.
• 25:18And you can see this,
• 25:19you know, estimates in the
• 25:21range of about six percent.
• 25:23It's pretty amazing that it's
• 25:24six percent in TAILORx, it's
• 25:26five percent in Mindac, it's
• 25:27five percent in,
• 25:29responder.
• 25:30And so that might lead
• 25:33in an unnuanced
• 25:34way for everybody to look
• 25:35and go, oh, no. We
• 25:36should we should be giving
• 25:37all these young women who
• 25:38are higher risk chemotherapy.
• 25:40But the obvious question for
• 25:42anybody who treats these patients
• 25:43is
• 25:44that what's really different about
• 25:46going from a premenopausal
• 25:48woman to a postmenopausal
• 25:50woman is the fact that
• 25:52premenopausal women still have ovarian
• 25:54function. And we've known for
• 25:56many, many, many, many years
• 25:58that ovarian function and turning
• 26:00off ovaries
• 26:01has a profound
• 26:03impact on breast cancer outcomes
• 26:05and control
• 26:06in the setting of now,
• 26:07we know, ER positive breast
• 26:09cancer. And so the the
• 26:11major question that confounds all
• 26:13of those studies is how
• 26:14much of that chemotherapy
• 26:15benefit
• 26:16in our premenopausal
• 26:18patients
• 26:19is due to the chemoendocrine
• 26:20effect of the chemotherapy.
• 26:23This is still a major
• 26:24outstanding question, and one of
• 26:26the clues that suggest that
• 26:27it may be
• 26:28all of it, if not
• 26:30a large part of it,
• 26:31it comes up to us
• 26:32from the TAILORx trial.
• 26:34Whereas you can see, if
• 26:36you look on the right
• 26:37in the blue areas,
• 26:38you know, there was a
• 26:39lot of work that's been
• 26:40done around clinical risk. And,
• 26:42of course, the higher clinical
• 26:43risk a person has,
• 26:45the higher the risk reduction
• 26:47a person might get
• 26:49from any given treatment. Right?
• 26:50The absolute benefits would be
• 26:52great. So if you take
• 26:53the recurrence score on the
• 26:54bottom and you say a
• 26:55recurrence score of twenty one
• 26:56to twenty five and they
• 26:57have a high
• 26:59clinical risk, the estimate is
• 27:00almost twelve percent absolute benefit
• 27:03from chemotherapy in someone like
• 27:05that under age fifty who
• 27:07falls in that group. So
• 27:08that feels like it's a
• 27:09no brainer to give them
• 27:10chemotherapy.
• 27:11And we know that our
• 27:12younger patients are not being
• 27:13screened.
• 27:14They're less likely to present
• 27:16with a smaller tumor. Right?
• 27:17Like we talked about, they
• 27:19have higher risks from the
• 27:20beginning. But wouldn't you know
• 27:21it? When we looked at
• 27:22the youngest patients in TAILORx,
• 27:25the forty and under,
• 27:27see where that hazard ratio
• 27:29is?
• 27:30No clear benefit. They're below
• 27:33one. So and it's not
• 27:34the tiniest of numbers. There's
• 27:36two hundred patients in that
• 27:37group. So what possibly could
• 27:39be going on there? And
• 27:40it's almost a dose response
• 27:42curve that you see. The
• 27:43older the woman is under
• 27:45the age of fifty,
• 27:47the more likely she is
• 27:48to get benefit from from
• 27:50chemotherapy, which flies in the
• 27:51face
• 27:52of all of the things
• 27:53we know about the benefits
• 27:55of chemotherapy.
• 27:56And and the point is
• 27:57that a lot of that
• 27:58probably is that the youngest
• 28:00patients are the least likely
• 28:02to get ovarian function
• 28:05suppression
• 28:06from chemotherapy
• 28:07personal
• 28:09permanently
• 28:10from the conventional chemotherapies that
• 28:13we use. So this really
• 28:14does remain a really important
• 28:16question.
• 28:17And in the meantime, when
• 28:18those studies were coming to
• 28:19fruition
• 28:20accrual,
• 28:21we also have the soft
• 28:23in text data, but particularly
• 28:24soft
• 28:25down the left that showed
• 28:27a very, very large six
• 28:30percent or five percent absolute
• 28:31benefit in disease free survival
• 28:34from just adding ovarian suppression
• 28:35to tamoxifen.
• 28:37And then if you give
• 28:38to in premenopausal
• 28:39women,
• 28:40and then if you give
• 28:42an aromatase inhibitor with that
• 28:43ovarian suppression, you see an
• 28:45even bigger bump. So at
• 28:47the same time that these
• 28:47studies were coming out, we
• 28:49were also seeing
• 28:51TexanSoft
• 28:52showing us that those old
• 28:53studies were not giving the
• 28:55best endocrine therapy backbone that
• 28:57they could possibly have. And,
• 28:58potentially,
• 28:59could these benefits somewhere between
• 29:01five to ten percent in
• 29:02higher risk young women,
• 29:04could they
• 29:05offset and be the reason
• 29:07that the chemotherapy is showing
• 29:09such a difference
• 29:10by that age or pre
• 29:12and postmenopausal
• 29:13status? Well,
• 29:15many of us have to
• 29:15practice in this, so we
• 29:16make decisions every day weighing
• 29:18the pros and cons and
• 29:19sharing those data with patients.
• 29:21Fortunately, there are two studies
• 29:23that are looking at this.
• 29:24This is the one in
• 29:25North America, the OFFSET trial.
• 29:26I don't know if you
• 29:27guys have it open here
• 29:28yet, but it's looking at
• 29:30randomizing women
• 29:32to chemo or no chemo
• 29:33who fall within the groups
• 29:35of that intermediate or low
• 29:37risk groups. And everybody gets
• 29:39to start with the best
• 29:41chemo I mean, the best
• 29:42hormonal therapy backbone in terms
• 29:44of risk reduction.
• 29:45You can see it here.
• 29:46It's an aromatase inhibitor plus,
• 29:48ovarian suppression.
• 29:49And there's a corresponding study
• 29:51in the UK,
• 29:53that one of our colleagues
• 29:54who we trained who I
• 29:55we trained with Inej Vazluiz
• 29:57is running now,
• 29:58across Europe that will be,
• 30:01testing the same thing in
• 30:02a cohort of patients in,
• 30:05in the UK. So we
• 30:06will have this answer at
• 30:08some point assuming these studies
• 30:10accrue. But in the meantime,
• 30:11we do make decisions.
• 30:13And, you know, I think
• 30:14it's really important to know
• 30:15that ovarian suppression is is
• 30:17a really important therapy for
• 30:18our patients,
• 30:19and it does add to
• 30:21tamoxifen or an aromatase inhibitor.
• 30:23It is a powerful
• 30:25risk reducer. By itself,
• 30:27adds
• 30:27thirty percent over tamoxifen alone
• 30:29and adds even more when
• 30:30it's given with an aromatase
• 30:32inhibitor.
• 30:33Not so clear that it
• 30:34adds as much in people
• 30:35who got chemotherapy,
• 30:37but isn't ovarian suppression a
• 30:39nicer way than chemotherapy to
• 30:41have that that functional effect
• 30:43for some, maybe for some,
• 30:44maybe not so much if
• 30:45someone's not gonna be adherent.
• 30:47And there are cost to
• 30:48ovarian suppression treatment.
• 30:50The side effects,
• 30:52the time and financial toxicity
• 30:54of coming into a cancer
• 30:55center every, you know, one
• 30:56to three months, maybe every
• 30:58six months. I end as
• 31:00we can test the six
• 31:01month regimens in our young
• 31:02people. So and this can
• 31:03really impact on how a
• 31:04person,
• 31:06how a person tolerates therapy.
• 31:08Adherence is a huge issue.
• 31:10That's something that we also
• 31:11studied
• 31:12before our young women's cohort
• 31:14was off the ground. And
• 31:15these are old data
• 31:17from some Medicare and Medicaid
• 31:19datasets that I had the
• 31:20pleasure of working in. And
• 31:22way back when we showed
• 31:23that adherence wanes over time
• 31:24to Tamoxifen alone and that
• 31:26young age and black race
• 31:28were predictors of non adherence.
• 31:30We talked about how did
• 31:31disparities
• 31:32come up. They come up
• 31:32when you have effective therapies
• 31:34that people don't either use
• 31:35or access themselves to. And
• 31:36then Dawn Hirschman has taken
• 31:38this work and done a
• 31:39lot more with it, showing
• 31:40that both adherence matters
• 31:42as well as the fact
• 31:43that,
• 31:43again, young age, those less
• 31:45than forty patients were more
• 31:46likely to discontinue their hormonal
• 31:48therapy, and they were more
• 31:50likely to just non adhere,
• 31:52not take it as directed,
• 31:54even if they weren't completely
• 31:55stopping it. So this may
• 31:57be one of the bigger
• 31:58contributors
• 31:59to why young patients
• 32:01don't do as well,
• 32:04beyond some of the biology
• 32:05as I showed you in
• 32:06the presenting with larger larger
• 32:09tumors and
• 32:10things. Interestingly, and these are
• 32:11hot off the presses data
• 32:13from this year's ESMO,
• 32:16there was a group across
• 32:17France that has modeled out
• 32:19using
• 32:20French national health system data
• 32:23the potential
• 32:24impact
• 32:25of if all young women
• 32:27were adherent. And they showed
• 32:29in their data set that,
• 32:30of course, like we've seen
• 32:31in America and other data
• 32:32sets, younger patients have lower
• 32:35persistence with endocrine therapy. And,
• 32:37again, it's very clear that
• 32:38it goes down,
• 32:40down with age,
• 32:42and it's very, you know,
• 32:43again, a dose response curve
• 32:44almost.
• 32:45And our young patients in
• 32:47France as well have, worse
• 32:49disease free survival. Again, some
• 32:50of it may be biology,
• 32:51but clearly, there's a link.
• 32:53We know adherence matters.
• 32:55And then they modeled out,
• 32:56which I thought I've thought
• 32:58about this for years, but
• 32:58I'd never seen anybody do
• 33:00it.
• 33:02What would happen if those
• 33:04women under thirty five where
• 33:05we see the worst outcomes,
• 33:08what would happen if we
• 33:09model out scenarios
• 33:11that just prevented them from
• 33:12discontinuing their endocrine therapy? In
• 33:14the fantasy world that you
• 33:15could kind of tie them
• 33:16down and do, like, direct
• 33:17observe therapy. Like, nobody's gonna
• 33:18do that. But but they
• 33:20modeled it out. And as
• 33:21you can see here,
• 33:22if
• 33:23French women took their hormonal
• 33:25therapy,
• 33:26they would have almost a
• 33:28six percent improvement
• 33:30in
• 33:31survival
• 33:32at five years. So pretty
• 33:34compelling data to continue to
• 33:36think about how do we
• 33:37optimize adherence, how do we
• 33:39help people to understand
• 33:40the importance of these drugs,
• 33:42how do we help them
• 33:43tolerate
• 33:44these drugs because these are
• 33:45some of the best tools
• 33:46we have
• 33:47against ER positive breast cancer
• 33:50for sure.
• 33:51And one of the areas
• 33:52where I focused on and,
• 33:54again, some of this was
• 33:55about, you know, when I
• 33:56was the the we taught
• 33:57working in Eric's clinic, I
• 33:59was a we wanting to
• 34:00be a mom myself, and
• 34:03a lot of women were
• 34:03coming in and saying, you
• 34:05know,
• 34:06wait. You're gonna give me
• 34:07hormonal therapy, and I have
• 34:09to take it. At that
• 34:09time, it was only five
• 34:10years. We didn't have the
• 34:11ten year data yet. I
• 34:13have to take it for
• 34:13five years, and this was
• 34:14you know, this this bump
• 34:15was diagnosed in the obese
• 34:18office. I my friends are
• 34:19all having their babies now.
• 34:20What are you telling me?
• 34:22And, you know, one of
• 34:23the things that we documented
• 34:25both with the young survival
• 34:26coalition years ago and then
• 34:28through our young women's cohort
• 34:29over time, and this is
• 34:30data from Katie Ruddy and
• 34:31Phil Porvoo in our in
• 34:33our group
• 34:34originally was that, you know,
• 34:35fertility was just a huge
• 34:37issue for these young women
• 34:38that wasn't getting a lot
• 34:39of attention way back when.
• 34:41Fortunately, over the last two
• 34:43decades, we've all been paying
• 34:44more attention to it. But
• 34:45you can see here, it's
• 34:46an issue both at diagnosis
• 34:48and then issue. And this
• 34:49is all forty and under.
• 34:51And and it's an issue
• 34:51that kind of still is
• 34:53there in longer term survivorship.
• 34:54And even if women
• 34:56are not going to go
• 34:57on and have a biologic
• 34:59child, helping them
• 35:01to acknowledge that loss and
• 35:03grieve it, bringing you know,
• 35:04we bring in the social
• 35:05workers at the beginning,
• 35:06but but there's also probably
• 35:08a need for attention to
• 35:09this in the long term
• 35:11follow-up, recognizing it's hard to
• 35:12do that in our resource
• 35:13constrained trained environment. But it
• 35:15can be a reason for
• 35:16some, and for many women
• 35:18that I've been told who
• 35:19are, you know, who are
• 35:20in this, it's even more
• 35:21impactful on their day to
• 35:23day emotional health than the
• 35:25cancer itself and the fear
• 35:27of recurrence, although that is
• 35:28impactful for many
• 35:30in this young cohort. So
• 35:31a really important area. When
• 35:33we dug deeper in the
• 35:35young women's cohort
• 35:36about kind of what was
• 35:37going on here and, you
• 35:38know, was it really something
• 35:40that might be impacting on
• 35:41their adherence as others had
• 35:42shown? We found that
• 35:44about a hundred and sixty
• 35:46women, so twenty six percent
• 35:47of those who had reported
• 35:49that they were cared about
• 35:50fertility,
• 35:51said that it affected their
• 35:53treatment decisions. Right. So it
• 35:54was impacting on the things
• 35:56that reduce risk. This is
• 35:58where
• 35:58survivorship
• 36:00meets survival.
• 36:01So if anybody thinks that
• 36:03survivorship is just make people
• 36:04feel good, which is a
• 36:05good thing and an end
• 36:06in and of itself,
• 36:07I think the other critical
• 36:08thing is if we don't
• 36:09take good care of our
• 36:10survivors and help to meet
• 36:11them with for their needs,
• 36:14they're gonna speak with their
• 36:15feet around things that actually
• 36:16impact their survival. So these
• 36:18two things need to be
• 36:19super hand in hand when
• 36:21we plan our cancer centers
• 36:22and when we think about
• 36:23interventions.
• 36:25And what we showed when
• 36:26we dug deeper is that,
• 36:28sure, most people were kind
• 36:29of taking their therapies,
• 36:31but ninety people told us
• 36:33that, you know, four of
• 36:34them, one percent chose not
• 36:35to get chemo. Maybe it
• 36:36was a real choice and
• 36:37the benefits would have been
• 36:38small.
• 36:39Two percent chose one regimen
• 36:41over the other. Interesting.
• 36:43One percent considered not receiving
• 36:44endocrine therapy, considered it. Three
• 36:47percent actually chose not to
• 36:48receive endocrine therapy, and eleven
• 36:50percent said they wanted to
• 36:52take less than the five
• 36:53years.
• 36:55And you can see how
• 36:56and this is a group
• 36:57that's
• 36:58telling us
• 36:59this. They're participating in a
• 37:00longitudinal
• 37:01cohort study.
• 37:03These are the, like, the
• 37:03the people who are kind
• 37:04of doing what the doctor
• 37:05tells them to do. Now
• 37:06imagine what's happening in the
• 37:08real world
• 37:09around endocrine therapy adherence. That's
• 37:11why you see huge rates
• 37:12of nonadherence
• 37:13with, you know, hypertension. Well,
• 37:14they're not that much better
• 37:15with their anticancer therapies when
• 37:17they're given chronically.
• 37:18So
• 37:19this in part led to
• 37:21the
• 37:22positive trial.
• 37:23And the positive trial was
• 37:26a kind of
• 37:27multinational
• 37:28effort to try to help
• 37:30women who were facing that
• 37:32clinical conundrum of,
• 37:34I want my baby
• 37:35yesterday, and now I have
• 37:36to deal with this jail
• 37:38sentence of endocrine therapy. And
• 37:40I want to get good
• 37:41breast cancer care, but I
• 37:42don't wanna put my whole
• 37:43life on hold. I know
• 37:45I'm likely be a survivor.
• 37:46And, you know, I really
• 37:47don't feel like rolling the
• 37:48roulette,
• 37:49you know, at the roulette
• 37:50table and feeling like I'm
• 37:52taking chances in any way.
• 37:53Not that having a baby
• 37:54is a spectator sport. So
• 37:56the the goal was to
• 37:57say,
• 37:58how can we help women
• 38:00to have best breast cancer
• 38:02care and at the same
• 38:03time
• 38:04not put their lives on
• 38:05hold? And so the study
• 38:06was designed
• 38:07to say, let's take a
• 38:08break from endocrine therapy.
• 38:10We know
• 38:11that the hazards of recurrence
• 38:13in women with ER positive
• 38:15breast cancer lasts for thirty
• 38:16years.
• 38:18We would typically stop you
• 38:19at five years of endocrine
• 38:20therapy or ten. What if
• 38:22we took a break and
• 38:23you still got five or
• 38:24ten years? Is that, you
• 38:25know, a year or two
• 38:27or three into it gonna
• 38:29make a much bigger difference
• 38:30than taking that break between
• 38:32years five and seven, which
• 38:33is what we were doing
• 38:34and, again, you know, conventionally?
• 38:37And we had a whole
• 38:38slew of data,
• 38:39retrospective, I'll be, that said
• 38:41women who went on to
• 38:42have a pregnancy after breast
• 38:43cancer
• 38:44seemed to do just as
• 38:45well as women who didn't
• 38:47go on to have a
• 38:48pregnancy, whether it was ER
• 38:50positive
• 38:51or ER negative, despite concerns
• 38:53that, you know, getting pregnant
• 38:55might throw gasoline
• 38:57on the embers of a
• 38:58recurrence.
• 38:59There was no data in
• 39:00the modern era that actually
• 39:03made that look like it
• 39:04was a reality, but still
• 39:05people were worried about. So
• 39:07this was also gonna look
• 39:08at that. But it was
• 39:09really testing the question of
• 39:10is an interruption
• 39:13a safe enough thing to
• 39:14do. Now as you can
• 39:16imagine, we couldn't do a
• 39:17randomized trial of this because,
• 39:19I don't know about you,
• 39:20but what person and their
• 39:21loved ones would go on
• 39:22the you get a baby
• 39:23and you don't get a
• 39:24baby study?
• 39:26Maybe someone, but we weren't
• 39:27that draconian. So what we
• 39:29did was a single arm
• 39:30trial modeling
• 39:32after you would go on
• 39:33that? Is that what you're
• 39:34saying?
• 39:35A single arm trial modeling
• 39:37after other work that had
• 39:39been going on recently where
• 39:40we set a threshold for
• 39:42safety.
• 39:43And you can see the
• 39:44schema at the bottom. We
• 39:45said, okay. What are people
• 39:46comfortable with? We made this
• 39:48decision. Again, multinational
• 39:50with, patient advocates at the
• 39:52table. There was a lot
• 39:53of back and forth on
• 39:54how long we were gonna
• 39:55make them take endocrine therapy.
• 39:57You know, obviously, we're not,
• 39:58again, not tying people down.
• 39:59Everybody thought it was safe
• 40:00enough to get at least
• 40:01eighteen months. And then we
• 40:03stopped the study at having
• 40:05taken at least thirty months.
• 40:06And the reason for that
• 40:07was to make it a
• 40:08real experiment
• 40:09because most people practically would
• 40:11say, oh, get at least
• 40:12three years because that's close
• 40:14to five years, and we
• 40:15know that five years is
• 40:16better than two years is
• 40:17better than one year. So
• 40:18it's very practical, but allowing
• 40:20women to do it a
• 40:21little earlier and then flexible.
• 40:23Look at the patients tolerate.
• 40:25Then they had needed to
• 40:26have a three month washout
• 40:28to get the endocrine therapy
• 40:29out of their system. They
• 40:30were supported to have a
• 40:32two year up to a
• 40:33two year break to get
• 40:34pregnant, however they could get
• 40:36pregnant,
• 40:37and then nurse if they
• 40:38wanted to and could, and
• 40:40then ideally get back on
• 40:41with a you know, that
• 40:42well, up to a two
• 40:43year window, and then we're
• 40:44following them for long term
• 40:46following. They would complete
• 40:47a five to ten year
• 40:48protocol depending on tolerance and
• 40:50what they decided about their
• 40:51basic risk.
• 40:53So who did we enroll?
• 40:54We enrolled
• 40:55this is our, you know,
• 40:56our popular our ITT population,
• 40:58five hundred and sixteen people.
• 41:01As you can see, they
• 41:02represent, you know, those who
• 41:03get young onset breast cancer.
• 41:05The majority,
• 41:06or the biggest group was
• 41:07between thirty five and thirty
• 41:09nine. When you look at
• 41:09our young women's cohort, the
• 41:11average age is thirty seven.
• 41:12So I think it's pretty
• 41:13spot on. That was forty
• 41:13and under.
• 41:15Most of the women who
• 41:16were doing this had not
• 41:17had a prior pregnancy, no
• 41:18surprise, those would be the
• 41:19ones that would be driven
• 41:21to do this interruption and
• 41:22be on the trial. And
• 41:23you can see that it
• 41:24was mostly patients with stage
• 41:26one and stage two disease.
• 41:28About six percent had stage
• 41:29three disease. I can tell
• 41:31you about forty percent had
• 41:32node positive disease. So it
• 41:33wasn't completely wimpy cancers.
• 41:36It was, you know, there
• 41:37were it was kind of
• 41:38what you tend to see,
• 41:40but the highest risk were
• 41:41not that well represented.
• 41:43Alright. Here's, I think, the
• 41:45most important outcome.
• 41:47I was that most women
• 41:48got pregnant.
• 41:49Most women. So seventy four
• 41:51percent of women had at
• 41:52least one person one pregnancy
• 41:54on the trial,
• 41:55and sixty four percent of
• 41:57the total or eighty six
• 41:59percent of those who got
• 42:00pregnant had at least one
• 42:02live birth. So that was
• 42:03that was pretty cool. That
• 42:04was really good news.
• 42:06There were some miscarriages. There
• 42:07were some abortions. I still
• 42:08have some patients
• 42:09that, you know, were on
• 42:10the trial and never got
• 42:11pregnant. Really heartbreaking and hard
• 42:13for them, and always challenging
• 42:14to get them back on
• 42:15the hormones.
• 42:17And then obviously the most
• 42:18important outcome that to the
• 42:20to us worrying about our
• 42:22patients recurring
• 42:23was the breast cancer free
• 42:24interval did not
• 42:26get as high as the
• 42:28prespecified
• 42:29safety threshold.
• 42:30There were forty four events
• 42:32in positive,
• 42:33and the threshold was set
• 42:35at forty six
• 42:36based on text and soft
• 42:38data.
• 42:40Now we had also
• 42:41conducted a calculated control cohort
• 42:44when we had about half
• 42:45of,
• 42:46positive accrued
• 42:48that controlled for BMI,
• 42:50nodal status, treatments received, including
• 42:53chemo, including AI or not.
• 42:55And that's the curve on
• 42:56the right for BCIFI,
• 42:58which is comparing the positive
• 43:00cohort
• 43:01to that TextSoft
• 43:03control analysis cohort, and there
• 43:05was no difference. If anything,
• 43:07the positive folks looked a
• 43:08little bit better.
• 43:10And this is a forty
• 43:11one month follow-up, which is
• 43:13about
• 43:14people were about two years
• 43:15on average after their diagnosis
• 43:18when they were enrolled. So
• 43:19this is about five year
• 43:20follow-up from their breast cancer
• 43:21diagnosis. So it's early days
• 43:23to see whether or not
• 43:24there's actual impact, but this
• 43:26was the primary outcome of
• 43:27the trial.
• 43:28What I think is the
• 43:29most important
• 43:30analysis in positive, which was
• 43:32buried in the supplement of
• 43:34the of the article,
• 43:35is this landmark analysis.
• 43:37And this was the people
• 43:39on positive.
• 43:40The top line is the
• 43:41people who didn't get pregnant
• 43:43by eighteen months and hadn't
• 43:45had a recurrence and then
• 43:46following them out. So the
• 43:47exposure is pregnant or not
• 43:49by eighteen months.
• 43:50Top line is not pregnant.
• 43:53Bottom line is the majority
• 43:54who got pregnant and not
• 43:56a snidge
• 43:58of signal
• 43:59that the pregnancy
• 44:00itself
• 44:01would impact on the risk
• 44:03of recurrence.
• 44:04So that, I think, is
• 44:06very, very reassuring
• 44:07and can kind of really
• 44:09corroborate
• 44:10all of the old data
• 44:11that we have that suggests
• 44:12that a pregnancy itself
• 44:14does not worsen a risk
• 44:16of recurrence
• 44:17in a breast cancer survivor.
• 44:19And we did this in
• 44:20a Cox model too and
• 44:21did not see if anything,
• 44:22the people who got pregnant
• 44:23looked a lot better, although
• 44:24I don't tell my patients
• 44:26to go out and get
• 44:26pregnant for treatment of their
• 44:27breast cancer for lots of
• 44:29good reasons.
• 44:30We've recently looked at some
• 44:31other secondary outcomes like time
• 44:34to pregnancy and no surprise.
• 44:36What was the biggest factor
• 44:37that predicted pregnancy?
• 44:39Age. The younger one was,
• 44:41the more likely she was
• 44:42to become pregnant, as you
• 44:43can see here.
• 44:45Interestingly,
• 44:46we looked at the chance
• 44:47of any pregnancy
• 44:49and age, of course, rang
• 44:50in there too. But the
• 44:51other big one that rang
• 44:53in there was the use
• 44:54of reproductive
• 44:56technology, the preservation
• 44:58of eggs or embryos
• 45:00or both
• 45:01before treatment. That was the
• 45:03other big predictor
• 45:05of pregnancy, and, obviously, that's
• 45:06independent of age. So what
• 45:08does that tell us? That
• 45:10tells us that we need
• 45:10to make sure that we
• 45:11have these services available for
• 45:13our patients, especially if they're
• 45:14older. We just looked at
• 45:16this in the young women's
• 45:17cohort. And you can see
• 45:18here, again, at the median
• 45:19follow-up of eleven years, and
• 45:20this includes ER positive patients
• 45:21and ER negative patients,
• 45:24we have similar numbers, which
• 45:25is incredible.
• 45:26Seventy three percent reported a
• 45:28pregnancy.
• 45:29Sixty five percent reported at
• 45:31least one live birth. It's
• 45:32really similar to positive, which
• 45:34is weird because it's not
• 45:35an overlapping group.
• 45:36The median time from diagnosis
• 45:38to first pregnancy in this
• 45:39cohort was forty eight months.
• 45:40Of course, we're gonna look
• 45:41at their longer term outcomes
• 45:42and their disease outcomes. But
• 45:44what we've modeled first is
• 45:46variables associated with pregnancy and
• 45:48variables associated with live birth.
• 45:49And in our cohort, it
• 45:50was financial comfort along with
• 45:52age and then fertility preservation
• 45:55along with age. So, again,
• 45:56the big signal here is
• 45:58we need to keep lobbying
• 46:00for insurers to pay for
• 46:01this and work within our
• 46:02systems to make sure that
• 46:03people are able to be
• 46:04referred in a timely fashion
• 46:06to get this important service
• 46:08if it matters to them.
• 46:10So now I'm gonna switch
• 46:11gears and just discuss for
• 46:13a few minutes what we've
• 46:14been doing now for almost
• 46:16two decades
• 46:17to try
• 46:18and
• 46:19get this information.
• 46:21All the things that we've
• 46:22been learning, we've known, and
• 46:23we've been learning. Because one
• 46:24of the things that we
• 46:25see at big cancer centers
• 46:27all the time is that
• 46:27someone comes in from the
• 46:28community
• 46:29and they're told, you know,
• 46:31you can't do that or
• 46:33that's unsafe, especially around the
• 46:35more nuanced stuff.
• 46:37And so in two thousand
• 46:38and five, again, with the
• 46:39support of my fearless mentor,
• 46:41we started the program for
• 46:43young women with breast cancer,
• 46:44and now we call it
• 46:45young adults with breast cancer.
• 46:47And this program addresses the
• 46:49critical issues that we've been
• 46:50talking about today that are
• 46:52unique to or accentuated by
• 46:54being young. We now call
• 46:55it young and strong,
• 46:57and it has four pillars.
• 46:58We focus on providing expert
• 47:00medical care. That's kind of
• 47:01what's unique to a big
• 47:03cancer center compared to all
• 47:04the advocates and all the
• 47:05other people that are doing
• 47:06really great space in this
• 47:07work.
• 47:08We offer comprehensive
• 47:10support. We try to build
• 47:12community among the young patients.
• 47:14And then, of course, we
• 47:15we conduct research to try
• 47:16and inform
• 47:17the care and the outcomes.
• 47:19These are our newest program
• 47:21introduction cards. We've you know,
• 47:23we try and make it
• 47:24pretty and appealing because there's
• 47:25so much coming at people
• 47:27every day from, you know,
• 47:29the world, including the cancer
• 47:30center, something that feels that
• 47:32it's resonating with them. You
• 47:33can see here.
• 47:35We also create a number
• 47:37of communications that are designed
• 47:38just for them. We have
• 47:39newsletters, e newsletters. We have
• 47:41a website.
• 47:42That's the web You can
• 47:43Google it if you want
• 47:43and send your patients there
• 47:44because it is very I
• 47:46think we have a lot
• 47:46of really great webinars and
• 47:46teaching sheets and things on
• 47:46there, and it's just the
• 47:47latest version of our newsletter.
• 47:48We have a lot of
• 47:50programming. Actually,
• 47:56we do about fifty virtual
• 47:59programs for our patients per
• 48:01year. We've moved into supporting
• 48:02our metastatic patients even more
• 48:04nowadays
• 48:05and have a virtual support
• 48:07group for them as well
• 48:08as for partners
• 48:10of those patients because it's
• 48:12so deep what they're dealing
• 48:13with over time.
• 48:15And so we try and
• 48:16do a lot. We partner
• 48:17with our social workers,
• 48:18for that very important work,
• 48:20a lot of sexual health
• 48:21things, all the things that
• 48:22are important to these patients.
• 48:24We actually just were funded
• 48:26through the CDC
• 48:27to do
• 48:28a contract
• 48:29to better engage with our
• 48:31communities
• 48:32writ large around the Greater
• 48:34Boston area so that we're
• 48:35not just serving the people
• 48:36that are able to get
• 48:37into our Dana Farber clinics
• 48:39and try and get more
• 48:41information out more into the
• 48:42community that we're calling that
• 48:44the yes project, and we're
• 48:45creating a bunch of resources
• 48:47that we hope to partner
• 48:48with groups like you so
• 48:49that when we create these
• 48:50things, there's no reason for
• 48:51people to reinvent the wheel.
• 48:53Hand it out, put your
• 48:54Yale sticker on it. We're
• 48:56happy to share so that
• 48:57things are disseminated
• 48:59everywhere it needs to be.
• 49:01We're not competitors here at
• 49:02all.
• 49:05Final thing is we've also
• 49:06tried to get our young
• 49:07women,
• 49:09our young, patient
• 49:11supports
• 49:12out beyond
• 49:14beyond cancer centers, beyond clinics.
• 49:17And we created something called
• 49:18Young Empowered and Strong, the
• 49:19web based portal,
• 49:21which is a PRO based
• 49:23text prompting
• 49:25kind of tool
• 49:26where if a woman endorses
• 49:28signs or symptoms or concerns,
• 49:31she gets information. You can
• 49:32see here there's anxiety. Okay.
• 49:34You're anxious.
• 49:35Let's give her some more
• 49:36information on managing anxiety. She's
• 49:38interested in fertility around treatment.
• 49:40Let's give her more information
• 49:41on that. If she doesn't
• 49:42endorse that as an issue,
• 49:44she doesn't get the information
• 49:45on that,
• 49:46but she can ask for
• 49:47it if she wants it.
• 49:48And we did a pilot
• 49:49of this. And as you
• 49:50can see here, what do
• 49:52the women trigger the most?
• 49:53Well, actually, if you look
• 49:54at the bottom, we're pretty
• 49:55good at treating pain. We're
• 49:57reasonably good at treating nausea,
• 49:59but there was nearly universal
• 50:01triggering
• 50:02of things like sexual health,
• 50:04menopausal symptoms, and mental health.
• 50:06And that doesn't mean we
• 50:07don't try, but there's a
• 50:08lot of need there. And
• 50:09so our hope, and we're
• 50:11now testing this in a
• 50:13number of studies, both at
• 50:14Dana Farber and then at
• 50:15MultiSites,
• 50:16to use this tool for
• 50:18our young adults, both at
• 50:19diagnosis,
• 50:21living with metastatic disease, and
• 50:23survivors to try and do
• 50:25more of a kind of
• 50:27self management of some of
• 50:29especially the stuff that's harder.
• 50:30You know, we don't have
• 50:30resources to take care of
• 50:32all of this stuff, but
• 50:33a lot of our young
• 50:34patients can self manage and
• 50:35self monitor these things. So
• 50:37we hope that we're able
• 50:38to move the needle in
• 50:39terms of serving them
• 50:40better through these kinds of
• 50:41tools.
• 50:42Stay tuned. The final thing
• 50:44I'll tell you about is
• 50:45something that we partner with
• 50:46an advocacy group called Bright
• 50:48Pink. They had a tool
• 50:49called assess your risk that
• 50:51would they had built
• 50:52and was sitting there on
• 50:53the web, and they got
• 50:54out of the kind of
• 50:55advocacy, and they're just fundraising
• 50:57now. And they gave us
• 50:58the tool, and we kinda
• 51:00Dana Farberized it. And now
• 51:02it's available
• 51:03online
• 51:04to go in for any
• 51:06patient to look at their
• 51:07risks of any woman. It
• 51:08doesn't have to be a
• 51:09patient. It's more for non
• 51:10patients, people who are previvors,
• 51:13and to look up their
• 51:14breast and ovarian cancer risks
• 51:16and put in their it's
• 51:18both about health behaviors, it's
• 51:19about family history,
• 51:21and it's using,
• 51:22tire, tear up music
• 51:24and other kind of, you
• 51:25know, things that are not
• 51:26in there, but we all
• 51:27know matter, like how much
• 51:29alcohol and whether or not
• 51:30they're exercising and whether or
• 51:31not they're obese. And so
• 51:33we've now activated that
• 51:36website as of last year,
• 51:37I think in January,
• 51:39and we've had something like
• 51:40a hundred thousand page views
• 51:43and over almost seven thousand
• 51:45unique views. And it's a
• 51:46pretty cool tool. So if
• 51:47anybody's interested in sending patients
• 51:49there or wants more information,
• 51:51it's it's a nice way
• 51:52for people when they when
• 51:53their friend is sitting next
• 51:54to them and saying, what
• 51:55do I need to know
• 51:56about breast cancer? And you
• 51:57don't have time, send them
• 51:58to this and they can
• 51:59kind of learn a little
• 51:59more. And there's a lot
• 52:00of teaching around it.
• 52:02So in conclusion,
• 52:04I
• 52:05would hope we agree today
• 52:07after all this that, younger
• 52:08women do, unfortunately, still have
• 52:10higher risk of recurrence and
• 52:11mortality from breast cancer,
• 52:13but there are a growing
• 52:15number of tools to reduce
• 52:16risk. All of the
• 52:18advances that we've made recently,
• 52:20like immunotherapy
• 52:21for triple negative breast cancer
• 52:23or the anti HER2 therapies,
• 52:25if anything,
• 52:26they're more likely to help
• 52:28our youngest patients because they're
• 52:29more likely to both develop
• 52:30those kinds of diseases
• 52:32proportionally
• 52:33as well as
• 52:34have more advanced disease that
• 52:36warrant that level of treatment.
• 52:38And so when over the
• 52:40next several years, I hope
• 52:41we continue to see improvements
• 52:43in terms of their mortality
• 52:44and recurrence risks.
• 52:46But on the flip side,
• 52:47I don't think we need
• 52:48to treat all young women
• 52:49with aggressive therapy, and we
• 52:50need to continue to interpret
• 52:52the data with a more
• 52:54nuanced view so our patients
• 52:55get their tailored therapy, not
• 52:57the sledgehammer of chemo and
• 52:59everything else, especially when, you
• 53:01know, you could do it
• 53:02with a more precise,
• 53:04scalpel.
• 53:05I think we do need
• 53:06to continue focusing research,
• 53:08on this population,
• 53:10not just because I do
• 53:11it but because the numbers
• 53:13are increasing.
• 53:14And we need to understand
• 53:15better who's at high risk
• 53:17and what's biologically unique about
• 53:19this population,
• 53:20if anything, so that we
• 53:21can develop better tools to
• 53:23target,
• 53:24their disease.
• 53:25And then finally,
• 53:27focused efforts to implement what
• 53:29we already know, whether it's
• 53:31adherence or getting better information
• 53:32about management of hot flashes
• 53:34or vaginal dryness for this
• 53:35population
• 53:36that shouldn't really be dealing
• 53:37with this at that age,
• 53:39is, I think, critical to
• 53:41taking better care of them.
• 53:42And I know, you know,
• 53:43we I just showed you
• 53:44our Young and Strong program.
• 53:45I know you guys are
• 53:45doing great work here in
• 53:47your Young Onset Cancer program
• 53:49led by Nancy and Vida.
• 53:51And so I'm I'm excited
• 53:53about our ongoing collaborations
• 53:54and all of that work.
• 53:55And I'd like to end
• 53:56with just saying thank you.
• 53:57Thank you to all of
• 53:58you for listening.
• 53:59Thanks especially to Eric,
• 54:02for supporting a lot of
• 54:03this work and supporting me
• 54:04over the years. And we
• 54:05have, of course, funders, and
• 54:07I have a whole team
• 54:07of people I've been working
• 54:08with for years both at
• 54:09Dana Farber and beyond.
• 54:11And then to me, it's
• 54:12really important to always infuse
• 54:14the patient voice into all
• 54:15of this. So many, many
• 54:17patients and advocates have, contributed
• 54:19to a lot of the
• 54:20work that, at least from
• 54:21our group over the years.
• 54:22So thank you.
• 54:29We probably have time for
• 54:30about two questions. Okay.
• 54:36Quick question about the, positive
• 54:38trial and
• 54:40recommendations
• 54:41you made in the trial
• 54:42setting breastfeeding after the delivery.
• 54:44That may have had any
• 54:46interaction with the outbreaks?
• 54:49So it's a great question.
• 54:51And we just looked at
• 54:52breastfeeding, and we just presented
• 54:54it. And the people there
• 54:55was no detriment to breastfeeding.
• 54:58They didn't appear to also
• 54:59be to add any good
• 55:00goodness. There was no there
• 55:02was no difference.
• 55:04The numbers get small, though,
• 55:06and there are a number
• 55:07of studies that are looking
• 55:08at this right now in
• 55:09the cohorts that are available,
• 55:10believe it or not. And
• 55:11it looks very feasible for
• 55:13a proportion of patients. I
• 55:14mean, obviously, if they have
• 55:15breast tissue, challenging on one
• 55:17side, but didn't didn't clearly
• 55:18impact on their breast cancer
• 55:20outcomes.
• 55:22Say they couldn't breast No.
• 55:24We encouraged it.
• 55:26Well, no. It was very
• 55:27personal. So we encouraged it
• 55:28if they wanted to, but
• 55:29we wanted them to get
• 55:30back on in within two
• 55:31years. But that doesn't mean
• 55:32that everybody listen. This is
• 55:33a very practical real world
• 55:35thing, and I had people
• 55:36who kept breastfeeding and didn't
• 55:37get back on. I mean,
• 55:38it's just the nature of
• 55:39the beast. So we'll be
• 55:40able to look at that
• 55:41over time, but the short
• 55:42term data using that same
• 55:44forty one months,
• 55:45it didn't hurt or harm.
• 55:49It's a good question.
• 55:55Oh
• 55:56oh, here. View. Let's see.
• 55:59Do we
• 56:01uncheck? Okay. Sorry. I'm Melissa.
• 56:06Do you see it?
• 56:09It just says, Andrew, can
• 56:10you share your question via
• 56:11chat? I don't know what
• 56:13happened. Did you have a
• 56:14question, Mary?
• 56:17Positive data are being
• 56:19twisted
• 56:20among
• 56:22certain circles
• 56:23as,
• 56:25that estrogen replacement therapy
• 56:27and postmenopausal
• 56:28years
• 56:29that this is proof
• 56:31that estrogen is not associated
• 56:33with increased breast cancer. Like,
• 56:34again, this this can you're
• 56:36you're being cited in circles
• 56:37you may not be aware
• 56:38of.
• 56:39People think I'm gonna be
• 56:40the baby whisperer. And sometimes
• 56:41people come to me, and
• 56:42I'm like, you can't have
• 56:43a baby right now.
• 56:46Yeah. I think it's a
• 56:47great question.
• 56:49And if if anybody didn't
• 56:50hear it, it's can we
• 56:51use the positive data to
• 56:52justify
• 56:53the free for all that
• 56:55we want? People are like,
• 56:56oh, I can just take
• 56:56a two year break in
• 56:57my endocrine therapy, or I
• 56:59can just add any hormone
• 57:01back because positive showed I
• 57:02could have a baby. And
• 57:03I think the answer is
• 57:05positive showed
• 57:06in short term follow-up that
• 57:08there was no clear short
• 57:10term detriment to an interruption
• 57:12for pregnancy. And the majority
• 57:14of these people had a
• 57:15pregnancy,
• 57:16some didn't. And, yeah, there's
• 57:18a little signal for a
• 57:19pregnancy might be a good
• 57:20thing, but it may all
• 57:21be healthy mother bias who's
• 57:23able to get pregnant. The
• 57:23body is funky. Right? Maybe
• 57:25the body doesn't get pregnant
• 57:26when it's having a recurrence
• 57:28that you don't even know
• 57:28about yet. So we just
• 57:30don't know. I would say
• 57:31long term, I would watch
• 57:32it, but I would not
• 57:33use it for a justification
• 57:35of anything else.
• 57:38It's a good question.
• 57:41Alright. Well Thank you.