Oncologic Anthropology: African Ancestry and TNBC

January 25, 2023

Yale Cancer Center Grand Rounds | January 24, 2023

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00:00Like. Well, good afternoon everyone,
00:05and thank you for joining us at
00:08a Cancer Center grand rounds.
00:09This is the annual Kingsbury Lecture ship.
00:14In honor of breast cancer,
00:16I have the profound privilege today
00:18to introduce Doctor Lisa Newman.
00:21She is a surgical oncologist and someone
00:23that I have been in for much of my career.
00:27She has a clinical and research practice
00:30dedicated to breast cancer management.
00:33Her formal title is chief of the
00:35section of Breast Surgery at New York
00:37Presbyterian Weill Cornell Medical Center,
00:39and she leads a multidisciplinary breast
00:42program at the David H Koch Center,
00:45also at New York Presbyterian.
00:47Doctor Newman is the new and founding
00:50medical director for the International Center
00:53for the Study of Breast Cancer Subtypes.
00:56And this was recently headquartered
00:58at Wild Cornell as part of
01:00Doctor Newman's recruitment,
01:02she obtained her undergraduate
01:04education at Harvard University and
01:07attended medical school completing
01:09and general surgery residency at
01:12the State University of New York
01:15Downtown Medical Center in Brooklyn.
01:17She went on to pursue fellowship
01:19training and surgical oncology at the
01:21MD Anderson Cancer Center and joined
01:23the faculty there as an assistant
01:25professor before going back to Michigan.
01:27Doctor Newman has really been a trailblazer
01:30in both her research and clinical care.
01:33This is focused on ethnicity related
01:35variation of breast cancer risk and
01:37outcome and the evaluation and management
01:40of high risk patients including
01:42applications for neoadjuvant chemotherapy.
01:44She has a very robust research program
01:47and disparities in breast cancer
01:49risk and outcomes and has really
01:51been lifted up as a national leader.
01:54In this space, I think on a personal note,
01:57she is known as a generous and kind
02:00and gifted mentor and clinician.
02:03And she shared a story with me
02:05earlier today about her willingness
02:07to give time in the ICU during COVID
02:10to call families to update them
02:12about their loved ones.
02:13And I think this anecdote is
02:15a testament to her character.
02:17So we are very excited to hear from
02:19Doctor Newman today about oncologic,
02:21anthropology, anthropology.
02:24Breast cancer disparities,
02:25triple negative breast cancer
02:27and African ancestry welcome.
02:36So it's a huge, huge honor to be talking
02:39to all of you at such an incredible
02:42esteemed academic powerhouses,
02:43the Yale Cancer Center.
02:45And I first have to express my very
02:48deep appreciation to Eric, who,
02:50because you have such an incredible
02:52leader of your Cancer Center,
02:54somebody who is a force of nature
02:56in and of himself and has been a
02:59leader in the breast oncology world
03:02for so many reasons and across so
03:04many different types of research.
03:06But because of his deep dedication
03:09to HealthEquity and disparity,
03:12simply because of who he is and his nature,
03:14it's been a large part to accredit
03:17to him that.
03:19Disparities research is a field
03:20of study in and of itself.
03:23And so young minds like Rachel and
03:26Elios have been able to do wonderful,
03:28very, very exciting work in this area
03:31because it was made possible by Eric.
03:34I really appreciate how you've stood
03:36by all of us overtime and made this,
03:38this, this field of research possible.
03:41So I am over the next few minutes going
03:44to talk to you about my work and what
03:47my team calls oncologic anthropology.
03:50Which is basically the intersection of
03:52research trying to understand how African
03:55ancestry in and of itself predisposes
03:57individuals to some of the high risk,
03:59biologically more aggressive cancers
04:02such as triple negative breast cancer.
04:06Now,
04:06the World Health Organization defines
04:08social determinants of health as the
04:11conditions in which people are born,
04:13grow, live, work, age,
04:14and a broader set of forces that
04:17shape daily life conditions.
04:18And nobody would dispute the fact
04:21that poverty is clearly going to be
04:24a determinant of a poorer health,
04:27since the unequal dispute distribution
04:29of wealth in this country leaves
04:31communities of color,
04:32such as African Americans and
04:34the Hispanic Latin next.
04:35Community with the higher rates of poverty,
04:39it's not surprising that to these
04:41issues will go hand in hand with other
04:45metrics of socioeconomic disadvantage,
04:47such as being uninsured and being unemployed.
04:50And then these socioeconomic disadvantages
04:54have a downstream effect on health.
04:57And so communities of color,
04:59such as African Americans and the
05:01Latinx community also have higher
05:03prevalence of metrics of poorer health,
05:06including being obese and
05:08poorly controlled hypertension.
05:10And then most recently we saw how
05:12this played out in terms of the
05:14consequences of COVID severity.
05:18However, the very unique history of
05:21individuals with African ancestry in
05:24this country has led to a very stark
05:27and quite large magnitude disparity
05:30in health outcomes for African
05:33Americans compared to white Americans.
05:35And of course, this dates back
05:37to the era of slavery,
05:39when African ancestry individuals had
05:43no autonomy over their own healthcare
05:45or their healthcare of their families.
05:48But even though slavery was
05:49abolished more than 150 years ago,
05:52the consequence is the legacy
05:53of it stays with us.
05:55Over several decades that
05:57followed the abolition of slavery,
06:00discriminatory banking
06:01practices such as redlining,
06:04permitted the banking industry.
06:06To essentially leave many generations
06:08of African American families trapped in
06:11neighborhoods where they could not own
06:14their own businesses or their own homes.
06:17And this led to them living over many
06:20generations and communities featuring
06:22more impoverished school systems,
06:24which ends up leaving them with fewer
06:27professional and educational prospects.
06:29And today we see these communities.
06:32Continuing to be characterized by
06:34other features that affect health,
06:36such as food deserts.
06:39Less available healthcare resources.
06:45And the mere accumulative experiences
06:48over a lifetime of discrimination and
06:51racism is now being studied in the
06:53field of research called Allostatic Rd.
06:56where we are learning that these
06:58types of experiences not only
07:00have an adverse impact on health,
07:02but they also seem to impact
07:04on inherent cancer burden.
07:08When you look at the specific
07:10problem of breast cancer,
07:11it's not surprising that these
07:13socioeconomic disadvantages that are
07:15so highly prevalent in the African
07:17American community is going to have
07:20an impact on the higher breast cancer
07:22mortality rates that we see in African
07:24Americans played out because of the
07:27advanced stage distribution that
07:28we see for breast cancer related to
07:31impaired access to a breast cancer
07:33diagnosis and proper treatment.
07:37So this very close correlation between
07:41socioeconomic disadvantage and African
07:44American identity leads many people
07:47to question whether racial ethnic
07:50identity has any biologic relevance at all,
07:53or is it purely and simply
07:57a sociopolitical construct?
07:59Well, the answer of course is that
08:03both defining components of racial
08:05identity are present and they
08:07are not mutually exclusive.
08:10How we self identify as well as
08:12how society labels us will very
08:14definitely impact on how we live,
08:16on where we live,
08:17and on how we access healthcare.
08:20However,
08:20there are also features of racial
08:23identity that are very closely
08:25linked to our ancestral heritage
08:28and these ancestral genetic.
08:30Factors will also have an impact on
08:33health metrics and on cancer burden.
08:38And we've actually known for many
08:40decades now that when it comes
08:41to a diagnosis of breast cancer,
08:43there are indeed other factors aside
08:45from socioeconomics that are impacting
08:47on the outcome disparities that we see.
08:50This slide is now nearly 20 years old
08:52and comes from a study that I and some
08:54colleagues from the Harvard School of
08:56Public Health it conducted where we
08:58simply pulled together all of the data
09:00in the published literature looking
09:01at breast cancer survival rates for
09:04black women compared to white women.
09:06After accounting for some
09:07measure of socioeconomics,
09:09and as you see here from the forest plot,
09:11the African American breast cancer
09:13patients have a statistically significant
09:15nearly 30% higher mortality hazard.
09:17And again, this is after accounting
09:21for socioeconomic status.
09:23Furthermore,
09:23there are several features of the
09:25breast cancer burden in the African
09:27American community that can't easily
09:29be ascribed to socioeconomics.
09:31For example,
09:32the younger age distribution and
09:33depending on which study you read,
09:35up to 40% of African American
09:37breast cancer patients are diagnosed
09:39younger than the age of 50,
09:41compared to only about 1/5 of white
09:43American breast cancer patients being
09:45diagnosed in this premenopausal age range.
09:48African Americans,
09:49as we will be discussing in this
09:51presentation.
09:52We also have a higher risk of the
09:54biologically aggressive patterns of
09:56breast tumors, the high grade tumors,
09:58the hormone receptor negative
09:59and the triple negative tumors.
10:01We have a higher population based
10:03incidence of a primary inflammatory
10:05breast cancer and there's also
10:07the very poorly understood higher
10:09population based incidence of male
10:11breast cancer in the African Community,
10:14African American community.
10:16And so we definitely,
10:17definitely need to be exploring
10:20tumor biology and genetics.
10:22If we're going to try to comprehensively
10:25understand disparities and
10:26breast cancer outcome.
10:28Now,
10:28you might assume that looking at
10:30clinical trials data would be the near
10:33perfect way of disentangling racial,
10:35ethnic,
10:36identity and socioeconomics
10:38from cancer outcomes.
10:39And this was the background,
10:42the motivation for a really
10:43important study that was conducted
10:45several years ago by Kathy Albain
10:47and colleagues looking at data
10:49from the Southwest Oncology group.
10:51And in this study,
10:52they pulled together the outcomes for a
10:55whole variety of adjuvant therapy trials.
10:57For different types of cancers
10:59and they wanted to see if equal
11:02outcomes were achieved in the context
11:04of delivering equal care through
11:06participation in a clinical trial.
11:08Now happily,
11:09they did show that for the cancers
11:11that they looked at,
11:13outcomes did equalize given equal
11:15treatments regardless of racial,
11:17ethnic identity,
11:18except when it came to specific cancers.
11:21And for the hormonally driven cancers
11:23such as breast cancer and prostate cancer,
11:26the African-American clinical trial.
11:28Participants continue to have
11:31statistically significant worse outcomes.
11:33So many of us that have dedicated
11:35our careers to disparities research,
11:37we're really excited about Kathy study
11:39because we felt that it was going
11:41to usher in a whole new generation
11:43of young people interested in
11:45studying tumor biology and genetics
11:47and looking at cancer outcomes.
11:50We were there for a little dismayed
11:53at thefactthattime.com reviewed her
11:54study and called it an example of
11:57racial profiling in medical research.
11:59So this we were happy that her study was
12:01getting a lot of publicity, of course.
12:03But this title was a little dismaying,
12:06because of course, racial profiling has
12:07a lot of very negative connotations,
12:10and appropriately so.
12:11When it comes to racial profiling and,
12:14for example, the criminal justice system,
12:16but when it comes to cancer biology
12:20and studying cancer outcomes,
12:22racial profiling, if you will,
12:23is really just an example of epidemiology.
12:26And we absolutely have an obligation
12:28to study all of the characteristics
12:30of our patients when we're trying to
12:33understand why some cancer patients have
12:35a better or worse outcome than others.
12:37And this does include characterizing the
12:40racial ethnic identity of our patients.
12:43An example of how important this
12:46racial characterization of our
12:48cancer patients is is shown on the
12:51graphic to the left on this slide,
12:53where we're looking at the most
12:55basic of epidemiologic statistics,
12:57population based incidence rates of
12:59breast cancer and population based
13:01mortality rates from breast cancer
13:03over the last several decades.
13:04As documented by the surveillance,
13:06epidemiology and end results program.
13:08And what we see here is that over time,
13:11incidence rates of breast cancer
13:12historically have been lower for
13:14black women compared to white women.
13:16But the rates typically changed in parallel,
13:19indicating comparable effects of
13:21different environmental factors.
13:22But for mortality rates,
13:23shown by the two curves at the
13:25bottom of this slide,
13:27the mortality rates from breast cancer
13:28were equal for black women and white
13:30women until we reach the early nine,
13:32eight, 1980s and at that point.
13:35Mortality curves separate
13:36predominantly because of declining
13:38death rates and white women,
13:40but largely unchanging rates in black women,
13:43and this is probably because the advent
13:46of tamoxifen as our first endocrine
13:49targeted therapy for breast cancer.
13:51The effects of tamoxifen become
13:53apparent by the early 1980s,
13:55but as shown by the bar grift
13:58to the right of this slide,
14:00since African American women have
14:03significantly lower frequencies.
14:05Of the estrogen receptor positive
14:07cancers and higher rates of estrogen
14:09receptor negative to tumors.
14:11We are just not benefiting from
14:14the advantages of terrific systemic
14:16therapies such as tamoxifen to the
14:18same degree as our sisters from
14:21other racial ethnic backgrounds.
14:23So we basically by the early 1980s are
14:25seeing the unmasking of differences in
14:28tumor biology between African American
14:30and white American breast cancer patients.
14:32So now of course we've gone far
14:34beyond simply characterizing
14:36breast cancer as the dichotomous
14:38hormone receptor positive versus
14:39hormone receptor negative tumors.
14:41And we know that breast cancer isn't
14:44comprised of an entire spectrum
14:46of intrinsic tumor subtypes with
14:48the basal subtype being one of
14:51the more virulent subtypes.
14:53The the patients that we see everyday
14:55in clinic are not necessarily
14:57going to get complete genomic
14:59profiling done on their tumors.
15:01So we use immunohistochemistry
15:03to look at estrogen receptor,
15:05progesterone receptor and hormone and
15:07her two new expression as a convenient
15:09way to have a surrogate for identifying.
15:11The most aggressive of these tumors?
15:14And the triple negative breast
15:16cancers do tend to correlate with
15:18identifying a patient that has
15:20an intrinsic basal type tumor.
15:22It's not a perfect correlation,
15:24but it is pretty close.
15:26And as shown by the curves on
15:28the top right of this slide,
15:30women that have the triple negative
15:32breast cancers at every stage of breast
15:35cancer diagnosis have worse outcomes
15:37compared to the women who have the
15:39non triple negative breast cancers.
15:41And we now know from many studies that
15:43have been done that African American
15:45women have higher frequencies of triple
15:48negative breast cancers regardless of
15:49the age at which they're diagnosed.
15:51And we have higher frequencies of triple
15:54negative breast cancer regardless of the
15:57stage that the breast cancer is diagnosed.
16:00Now there's been an interesting
16:02phenomenon over the past couple of
16:04decades where the population based
16:06incidence rates of breast cancer
16:08have been rising disproportionately
16:10in African American women.
16:12And now over the last ten years or so,
16:15breast cancer incidence rates are pretty
16:17much equal for black women and white women.
16:20But those rising incidence rates
16:22of breast cancer in black women,
16:24coupled with our higher incidence of
16:26the triple negative breast cancer has
16:28resulted in a widening of the mortality gap.
16:31And today we see about 40% higher
16:34breast cancer mortality rates in the
16:36African American community compared
16:38to the White American community.
16:40And it's impossible to have a discussion
16:43about triple negative breast cancer
16:45and disparities without making
16:47some comment regarding mammography
16:49screening recommendations.
16:50And as I'm sure all of you are aware,
16:52the United States Preventive Services
16:54Task Force has been advocating pretty
16:57aggressively for average risk American
16:59women to delay initiation of screening
17:02mammography until they reach age 50.
17:04Many of us that are dedicating our careers
17:07to studying breast cancer disparities
17:09are really concerned about this.
17:11Broad recommendation,
17:12because waiting until age 50 for
17:16mammography screening can result in
17:18an even worsening of the delays in
17:21diagnosing biologically aggressive tumors,
17:24such as triple negative breast cancers,
17:25in African American women,
17:27who are already at higher risk for getting
17:29these aggressive tumors at younger ages.
17:31And so this screening recommendation
17:34will likely worsen the
17:35disparities that already exist.
17:37Now,
17:37the critics of screening mammography
17:39are always quick to point out that
17:41mammography is not going to be the be all,
17:43end all answer to addressing
17:45disparities because it it is true
17:48that triple negative breast cancers.
17:50Are more challenging to detect on
17:53screening mammography and they're
17:54more likely to present it as the
17:57palpable interval cancers and women
17:58that are getting their screening
18:00mammograms every year.
18:01However,
18:02we do have very strong data showing
18:04that early detection of triple negative
18:07breast cancer does still make a difference.
18:10And an example of those data are shown
18:13in the two tables on this slide where
18:16investigators from Memorial Sloan
18:17Kettering and from the National
18:20Comprehensive Cancer Network.
18:21Have both demonstrated that triple
18:23negative breast cancer when it's
18:25diagnosed at a small size no larger
18:27than one centimeter in size.
18:29And with nodes negative and these
18:30are by and large going to be screen
18:33detected triple negative breast cancers.
18:34These tumors have very good outcomes
18:37regardless of whether the patients
18:39receive adjuvant chemotherapy or not.
18:42Now those two studies that I
18:43showed on the previous slide,
18:45we're looking at early detection
18:46of triple negative breast cancer,
18:48but they weren't necessarily
18:49looking at mammography,
18:51screen detected triple
18:52negative breast cancer.
18:54And so to address the question of how
18:57effective screening mammography is
18:58and outcomes in improving outcomes
19:01from triple negative breast cancer.
19:03Our group pulled together the data
19:05on triple negative breast cancer
19:07patients from the Metropolitan Detroit
19:09area and the Henry Ford Healthcare
19:11system and the while Cornell New York
19:14Presbyterian Hospital network triple
19:16negative breast cancer patients.
19:18And we looked specifically at outcomes
19:20from for these patients if with triple
19:22negative tumors based upon whether it
19:24was screened detected disease or not.
19:27And we looked at a whole bunch
19:28of different factors that might
19:30also impact on outcomes from
19:31triple negative breast cancer.
19:33For both the white and the African
19:35American triple negative breast cancer,
19:36having a mammography screen detected
19:39tumor was the strongest predictor
19:41of a patient that was going
19:43to have a good outcome.
19:45So we do indeed have data that
19:47mammography screening is effective
19:49at early detection of triple negative
19:51breast cancer and it does yield some
19:54benefits in terms of improving outcomes
19:56and that benefit was actually strongest
19:58for the African American women.
20:01We've also been looking at whether
20:03or not there might be some precursor
20:05lesions in benign breast tissue,
20:07identifying women that are at higher
20:09risk for getting a triple negative
20:11breast cancer and whether or not the
20:14benign breast patients who require
20:16biopsies will still have a higher
20:19rate of triple negative breast cancer.
20:21Correlating with racial ethnic identity.
20:23As all of you are aware,
20:25the number of benign breast pie oopsies
20:27that a patient has does correlate with
20:29a higher risk of a future breast cancer.
20:31Probably because it's identifying
20:33hyperproliferative changes in the
20:34breast and This is why number of
20:37biopsies and so integrated into
20:38many of our risk prediction tools
20:40such as the Gale model.
20:41But by and large multiple biopsies
20:44is a predictor of having an estrogen
20:47receptor positive breast cancer.
20:49So we utilize the Henry Ford Health
20:51system benign breast disease cohort
20:53to look at whether fibrocystic breast
20:56biopsies predicted for higher rates
20:58of triple negative versus hormone
21:01receptor positive.
21:01Disease in our black compared to
21:03white patients and we had a very
21:06large cohort of more than 6000 women
21:08who had had benign breast biopsies
21:10with robust follow-up of more than
21:1310 years and in as evidence that
21:15these women were receiving equitable
21:18treatment over the years.
21:20We actually saw comparable rates of
21:22subsequent subsequent breast cancers
21:24in these women with fibrocystic
21:26breast changes regardless of
21:27whether they were black or white.
21:29And we saw comparable stage
21:31distribution for the cancers that
21:33did develop in these patients.
21:34However, as shown by this curve by the
21:37curve graphic at the bottom of this slide,
21:39the African American women with
21:41benign breast biopsies had about a
21:43four fold higher risk of getting
21:45a triple negative breast cancer
21:46compared to the white American breast
21:49fibrocystic change at patients.
21:50And so there does,
21:51at least from our experience seem to be
21:54something inherently different about
21:56the mammary tissue of African American
21:58women increasing the susceptibility for
22:01these biologically aggressive tumors.
22:03Another interesting question to
22:05ask is whether or not outcome
22:07disparities will persist after you
22:10stratify for tumor phenotype.
22:12And I'm not going to belabor the
22:14data on this very busy slide,
22:15but suffice it to say there are
22:17actually a number of studies
22:19suggesting that when you.
22:20Adjust for stage and treatment that
22:23the outcomes from triple negative
22:25breast cancer patients might
22:26actually be fairly comparable for
22:28black women and white women.
22:30However,
22:30there are numerous studies showing that for
22:33hormone receptor positive breast cancer,
22:35the disparities persist.
22:36Now,
22:37whether or not these disparities and
22:39outcome in hormone receptor positive
22:41disease are related to differences
22:43in tumor biology or difference in
22:46response to endocrine treatment
22:47or just variation in compliance
22:49with the several years that we
22:52recommend for endocrine therapies,
22:53these are all questions that
22:56are continue to be under study.
22:59But now we are starting to generate
23:01some answers to those questions because
23:04a brilliant researchers who've been
23:06conducting terrific studies about
23:08gene expression profiling in women
23:11with hormone receptor positive,
23:13her two negative breast cancers are
23:15now starting to look at their data
23:19based upon stratification for race ethnicity.
23:21The TELERX investigators have recently
23:24shown that for women undergoing
23:26Oncotype 21 gene recurrence score
23:29testing for hormone receptor positive,
23:31her two negative and no negative
23:33breast cancers that in women
23:35with the intermediate scores,
23:37the African American women have
23:40notably higher rates of recurrence
23:42and mortality even after adjusting
23:45for these intermediate range scores.
23:49And then very recently the investigators
23:52for the responder trial reported
23:54and the San Antonio Breast Cancer
23:56Symposium that among women looking
23:58at these 21 gene recurrence scores
24:01and whether or not they predict for
24:03benefit from chemotherapy in the
24:05setting of women with no positive disease.
24:07They similarly showed that the
24:09outcomes for the African American
24:11patients were significantly worse
24:12compared to the outcomes for
24:14the White American patients.
24:16And again this is after stratifying.
24:19For the 21 gene expression score.
24:25Many investigators have been looking
24:27at data from the Cancer Genome Atlas
24:29to try to get take a deeper dive,
24:31basically into looking at tumor
24:34biology between black women and
24:36white women with breast cancer.
24:38And I'm summarizing just a few of
24:41the studies that have been published
24:43utilizing TCG a data on this table.
24:46But all of these studies are basically
24:48looking at the same group of,
24:50you know, more than 700 white
24:53American breast cancer patients.
24:54And about 170 African American
24:57patients that have contributed tumor
24:59tissue and clinical information.
25:02So it's not surprising that all
25:04of these investigators have
25:06identified similar patterns.
25:08Pam 50 subtyping definitively showing
25:10that the African American women
25:12not only have higher frequencies
25:14of the triple negative
25:16immunohistochemically defined phenotype,
25:17but we also have higher rates
25:20of the intrinsic basal subtype.
25:22The African American patients are
25:24more likely to have TP 53 mutations
25:27and fewer Pi K3CA mutations,
25:29which goes along with the higher
25:31frequency of triple negative and
25:33lower frequency of hormone receptor
25:35positive tumors in these patients.
25:39And the phenomenon of seeing higher
25:41rates of these biologically aggressive
25:43estrogen receptor negative and triple
25:46negative breast cancers in women
25:48with African ancestry is actually
25:50not something that's unique to the
25:53United States and other countries.
25:55The UK, Switzerland,
25:56Brazil investigators from these
25:58countries have also published data
26:01showing that their African ancestry
26:03breast cancer patients are more likely
26:06to have estrogen receptor negative and.
26:09Triple negative breast cancers
26:11compared to their non African
26:13ancestry breast cancer patients.
26:15So This is why our group has been
26:17very excited about looking at
26:18international data and in particular
26:20looking at the breast cancer burden
26:22of women on the continent of Africa,
26:23to try to tease out the answer to the
26:26question of whether or not African
26:28ancestry in and of itself is associated
26:31with some heritable marker predisposing
26:33to risk for triple negative breast cancers.
26:36And this I think opens the door not only
26:38to exciting ways to understand disparities,
26:41but also a very novel ways
26:43of trying to understand the.
26:45Pathogenesis for triple
26:47negative breast tumors.
26:50So this is just a snapshot of
26:52some of our most basic findings.
26:55Looking at the frequency of triple
26:57negative breast cancer in women from
27:00Ghana representing Western sub-Saharan
27:02Africa compared to the triple net,
27:04the frequency of triple negative breast
27:06cancers in women from Addis Ababa,
27:07Ethiopia, representing East Africa.
27:09And we see quite high frequencies
27:11of triple negative breast cancers
27:13in the economy and women,
27:15about half of them are triple negative,
27:17but the frequency of triple
27:18negative breast cancers.
27:19And the Ethiopian women is
27:21very low at about 15%,
27:24similar to what we see in White American
27:26and European patients with breast cancer.
27:29The frequency of triple negative breast
27:31tumors is intermediate for African
27:32American women between the rates
27:34that we see in Guinea and women and
27:36what we see in white American women.
27:39Now the American Cancer Society
27:42brilliant investigator,
27:43Ahmedin Jamal has to publish data
27:46that are comparable to what we're
27:49seeing in our international data set.
27:52Doctor Jamal has published data
27:53looking at the frequency of
27:55ER negative breast tumors,
27:57which of course are a subset of the
27:59triple negative breast tumors in white
28:01American breast cancer patients,
28:02African American breast cancer
28:03patients and women born in West Africa
28:06but whose cancers were diagnosed
28:08and treated in the United States.
28:10And women born in East Africa but
28:12whose breast cancers were diagnosed
28:13and treated in the United States.
28:15And similar to our international data,
28:17amadeen found that we see the highest
28:20frequencies of the ER negative
28:22tumors in the African American and
28:24West African born patients and the
28:26lowest frequencies of ER negative
28:28tumors in the White American and
28:31East African born patients.
28:33So this is where we've coined the
28:35nomenclature of oncologic anthropology
28:37to try to explain these patterns.
28:39And of course,
28:40as we all recall from grade
28:43school social studies,
28:44the transatlantic slave trade
28:46brought the ancestors of contemporary
28:49western sub-saharan Africans across
28:51the ocean to serve as slaves in
28:53the colonies. And so today,
28:56as contemporary African Americans,
28:58we have quite a bit of shared genetic
29:00ancestry with the contemporary Guineans.
29:03Representing Western sub-saharan Africans.
29:05But the slave trade from East Africa largely
29:09brought the ancestors of contemporary
29:12East Africans and Ethiopians further
29:14eastward to the Mideast and to Asia.
29:17And so as African Americans,
29:19we don't have quite so much
29:21shared ancestry with Ethiopia,
29:22excuse me, with Ethiopians.
29:23And so if there is something of
29:26a heritable nature related to
29:28African ancestry predisposing to
29:29triple negative breast cancer,
29:31it's likely something specifically related.
29:33Related to Western sub-saharan
29:36African genetic ancestry.
29:39So one of our terrific and brilliant
29:42research partners for my research team,
29:44the International Center for the Study of
29:47Breast Cancer Subtypes is Doctor John Carton,
29:49who runs the Translational Cancer
29:51Research program out at USC.
29:53And we've been really trying to work
29:55quite hard to get more of our colleagues
29:58in the oncology research world to look
30:01at the genetics of race and ethnicity
30:03and to quantify germline ancestral
30:05genetics with the cancer outcomes.
30:08As a way of trying to
30:10understand disparities better.
30:14So about five years ago,
30:16I was absolutely thrilled to be able
30:19to recruit one of John's mentees,
30:21Melissa Davis, who is a card carrying
30:24PhD geneticist to serve as the scientific
30:26director for our International Center
30:28for the Study of Breast Cancer subtypes.
30:31And our international team for the last
30:34nearly 20 years now has been building
30:37up this biobank biorepository of tumor
30:40specimens for somatic tumor tissue studies.
30:43And saliva specimens as well as blood
30:46specimens suitable for germline genetic
30:48studies from different parts of Africa.
30:51And so it was really exciting
30:53to get Melissa to serve as our
30:56basic science research leader.
30:57So that she could use her tools to
31:00tease out some of these differences
31:02and understanding the genetics
31:03of African ancestry.
31:05And for most of Melissa's career,
31:07she's been a world leading expert
31:09in studying a particular gene
31:11called the Duffy gene or the Duffy
31:14antigen receptor for chemokines.
31:15And there's a particular variant of
31:17the Duffy gene that is seen almost
31:20exclusively in individuals that have
31:22Western sub-saharan African ancestry.
31:24It's widely called the Duffy
31:27now Gene variant.
31:28And therefore this Duffy null variant
31:31is an ancestry informative marker
31:34informative of African ancestry.
31:37Now,
31:37Melissa's been studying Duffy
31:39null for most of her career.
31:41Other investigators have kind of happened
31:43a Long Duffy Knoll in the context of
31:46other studies looking at disparities.
31:48And this slide is summarizing
31:49the data from a study that came
31:51out of the Amber Consortium,
31:53a collaborative group of
31:55investigators looking at breast
31:56cancer disparities related to race.
31:58And in this particular publication,
32:00the Amber Consortium investigators were
32:02looking at levels of different circulating
32:04chemokines that might be associated with.
32:07Cancer and in particular breast cancer risk.
32:10And they wanted to see if the levels
32:12of these different keeps US cytokines
32:14were different between black women
32:16and white women who had not yet
32:18been diagnosed with breast cancer.
32:20And they did identify a handful
32:23of cytokines that differed between
32:25the black women and white women.
32:27And then when they did genetic analysis,
32:29they found that these differences
32:32were explained by the presence
32:34of the Duffy null genotype.
32:37We've also learned overtime that the
32:39Duffy Null variant is the variant
32:41that's responsible for a phenomenon
32:43called benign ethnic neutropenia,
32:46which is the fact that African
32:47Americans tend to have a lower
32:49circulating white blood cell count.
32:51Which doesn't have any biologic significance,
32:53but it is a numeric pattern
32:55that seemed pretty consistently.
32:57And some investigators are now
32:58looking at whether or not Duffy
33:00null may be implicated in transplant
33:02rejection disparities.
33:03And we are obviously looking
33:04at it in breast cancer,
33:06others are looking at it in
33:09prostate cancer disparities.
33:10Unfortunately,
33:11however,
33:11when you look at the literature globally,
33:14there is a huge gap in terms of what
33:17we know about how African ancestral
33:20genetics impact on cancer risk because
33:23so few of the genomic studies have
33:26included significant numbers of
33:28individuals with African ancestry.
33:30And as shown by this study from cell,
33:33only about 2% of individuals
33:36contributing to genome wide association
33:39studies have had African ancestry.
33:41So we were really excited to have
33:44Melissa work her magic with her
33:46genetics skills to apply them to
33:48our international biorepository,
33:51which again has been amassing
33:54specimens for nearly 20 years.
33:56So I'm Melissa did a really cool
33:59study where she looked at Duffy
34:01Null compared to a series of other
34:04genetic variants that have been
34:06potentially linked to risk of breast
34:09cancer and hormone receptor negative,
34:11triple negative breast cancer.
34:12And in working with this
34:15other brilliant researcher,
34:17our geneticist,
34:18biostatistician yallah chin from
34:21the Henry Ford Health system,
34:24Yalley was able to show that the
34:26presence of this Duffy Null variant
34:28was by far and away the strongest
34:31determinant of having a triple
34:33negative breast cancer versus having
34:35a non triple negative breast cancer.
34:39The phenomenal anthropologist Dr.
34:42Sarah Tishkoff has shown us very nicely,
34:46as demonstrated by this graphic,
34:49that many of the ancestry informative
34:52markers that we look at aren't markers
34:55variants that developed randomly over time.
34:58Many of them actually represent evolutionary
35:02selection pressure over our ancestors
35:05to to allow our ancestors to survive.
35:09Different threats to longevity,
35:12threats to life expectancy,
35:14related to infectious diseases,
35:16related to climate,
35:17related to food sources.
35:20And then today,
35:21when we look at the descendants
35:23of those populations,
35:24you can you can continue to see many
35:26of these ancestry informative markers,
35:28regardless of where the
35:29descendants reside over the globe.
35:34The Duffy Null variant is just one more
35:36example of such a variant that was acquired
35:39over the millennia as a consequence
35:42of evolutionary selection pressure.
35:44The Duffy Novariant is something
35:46that became apparent that was adopted
35:49in Western sub-Saharan Africa
35:51many many thousands of years ago,
35:54linked to the need to have
35:56some resistance to malaria,
35:58and malaria became endemic in
36:00Western sub-Saharan Africa because
36:01of the tropical nature of that.
36:03With the geography there with the many
36:06watery areas and low altitude areas
36:08supporting the lifecycle of the mosquito,
36:11which of course is the host
36:14for the malaria parasites.
36:16And there are other examples of variants
36:19that were acquired to confer some
36:21resistance to malaria that thalassemia is
36:24seen in European Mediterranean populations.
36:27Sickle cell,
36:28the Duffy Null variant,
36:30doesn't have quite as many of the adults
36:33health consequences as those variants do,
36:36and therefore the Duffy null variant is
36:39seen in nearly 100% of the descendants
36:43of Western sub-saharan Africans.
36:45Something occurred about 5-6 thousand
36:48years ago called the Band 2 expansion,
36:51where Western sub-saharan Africans
36:53migrated across the continent
36:55to populate the various areas of
36:58East Africa and South Africa.
37:00And while many of those areas have
37:02more mountainous areas that do not
37:04support the mosquito life cycle,
37:06so they have a different history of
37:08endemic malaria in those parts of the
37:11continent but with the Bantu expansion.
37:13The Duffy Null variant did track
37:15across the continent of Africa and
37:17you see varying degrees of admixture
37:19and the presence of this stuffy null
37:22variant in those reasons of Africa.
37:24Just as with the transatlantic slave trade,
37:28the Duffy Null variant came across
37:29to the Americas and with the genetic
37:32admixture that we see in African Americans,
37:34this results in about 2/3 to 3/4 of
37:36African Americans expressing that Duffy
37:38Null variant and if you overlay a map
37:41of the frequency of triple negative.
37:43Breast cancer in different parts
37:45of the world with a map of the
37:47the the Duffy Null variant,
37:49there's actually a pretty close correlation,
37:51so we've been exploring.
37:53Ways to understand how to connect
37:55the dots between the stuff we know
37:58variant and the risk of having a
38:01triple negative breast cancer.
38:02The reason why that Duffy Null
38:04variant confers some resistance to
38:06malaria is because if you possess
38:08the Duffy null variant,
38:09you do not express the Duffy
38:11protein on your red blood cell.
38:12And the Duffy protein on the red blood
38:15cell is kind of the entry portal for
38:17the malaria parasites to get into the
38:20red blood cell and cause the disease.
38:22So now what we are learning.
38:24And the work that's ongoing and
38:26Melissa let slip is seeking to better
38:29understand how this Duffy protein and
38:32lack of the Duffy protein on the red
38:35blood cell impacts on circulating chemokines,
38:37which would explain the findings
38:39of the Amber Consortium that I
38:42showed you previously.
38:43And how this may have a downstream
38:45in fact when the mammary tissue
38:47microenvironment and the
38:49inflammatory the immune landscape
38:51of the Mary mammary tissue.
38:52Which can then have an impact on the
38:54types of breast tumors that develop.
38:59Melissa has also been doing work with
39:02the Cancer Genome Atlas looking at
39:04tumor tissue expression presence of
39:06the the Duffy protein and you see as
39:09you would predict lower levels of
39:11Duffy protein in the breast tumors of
39:14African American compared to white
39:16women contributing specimens to TCG A.
39:18And the lower presence of a Duffy tends
39:21to correlate with worse prognosis
39:24across the different phenotypes.
39:26So this phenotype agnostic.
39:28If you will affect on tumor tissue
39:31tumor outcome may be what's explaining
39:34what we see in looking at the the
39:37the impact of race ethnicity on
39:40outcomes in women with that have ER
39:42positive disease as we saw from the
39:44tailor X and the responder trial.
39:48Many people are doing very,
39:50very exciting work seeking to subtype
39:53the triple negative breast cancers,
39:55and a lot of this work was pioneered
39:58by the Vanderbilt Group identifying
40:00about 6 different intrinsic triple
40:03negative subtypes initially.
40:05However, the publicly available
40:07datasets that contribute to to the
40:10definition of those different triple
40:12negative subtypes largely came from
40:15communities that had very few, if any.
40:18African ancestry individuals.
40:20So we really don't know if those
40:22triple negative breast tumor subtypes
40:23are applicable to the African
40:25ancestry populations that have a
40:27higher inherent risk of developing
40:29these triple negative subtypes.
40:32In working with Clayton Yates,
40:34who used to be at Tuskegee and and now
40:37he's recently relocated to Johns Hopkins,
40:40Clayton has also been utilizing data
40:43from our international buyer repository
40:45and has identified the fact that the
40:47triple negative breast tumors of
40:49African American women does seem to
40:51have different signatures compared to
40:53what we see in white American women.
40:59We're also utilizing data from TCG a
41:03Melissa's been looking at the impact
41:06of tumor infiltrating tumor associated
41:08lymphocytes on breast cancer outcomes.
41:11And we typically think of these
41:14tumor infiltrating lymphocytes as
41:16a favorable prognostic feature.
41:19But in this is these are unpublished data
41:21and these preliminary data from TCG a,
41:24the relationship seems to be
41:26flipped for African American women
41:28with the higher frequency.
41:29Of tumor associated lymphocytes seems
41:31to be an adverse prognostic feature.
41:37Data correlating with these findings
41:39from TCG A have been published,
41:43again by members of the Amber Consortium.
41:46This comes from a study published by
41:48Christine Andersoni and her group where
41:51they looked at the tumor microenvironment
41:53signature of breast cancers from African
41:55American and white American women.
41:57And while they did show that African
42:00American women tended to have a more
42:04robust tumor infiltrating lymphocyte.
42:06Content to their tumors,
42:08the lymphocytes of the African
42:10American women were more likely to
42:12have this T cell exhaustion signature,
42:15as they called it.
42:16And so their function was different
42:18compared to what we see in the what she saw,
42:20what they saw in the white American
42:22women with breast cancer.
42:26And this was an intriguing study that
42:28was published in Cell just a few years
42:31ago where some investigators were
42:33looking at immune cells that were
42:35basically primed with specific pathogens,
42:37infectious agents and then looking
42:39at the response of these immune
42:42cells from patients that were African
42:44American compared to white American.
42:46And they saw very distinct and
42:49different responses in terms of the
42:51immune activity of these immune cells.
42:53When they're linked to different pathogens.
42:57So you can only imagine that if the
43:00immune cells of African ancestry
43:02individuals are responding differently
43:04to infectious diseases compared to
43:06the immune cells of white individuals,
43:09there could easily be differences in
43:11the way these immune cells function
43:14in terms of cancer biology.
43:20So Melissa has been continuing to
43:22utilize our international data set
43:24in conducting other studies looking
43:26at the triple negative breast cancer
43:29risk alleles and I'm going to go
43:31through these next few slides quickly.
43:33In the interest of time,
43:34we've also been working with
43:36investigators from the University of
43:38Michigan been creating PDX models
43:40based upon our International Studies.
43:42And then very recently a couple
43:44of months ago,
43:44we were really excited about our work
43:47with triple negative breast cancer subtyping.
43:50Which was the cover article for cancer
43:52discovery a couple of months ago.
43:54So to us that was like being on
43:56the cover of our vogue magazines.
43:58We were very,
43:59very thrilled about this and we were
44:02able to show that looking at genetic
44:04ancestry does have independent meaning
44:07compared to self reported ancestry.
44:09And there were several 100 genes
44:12linked to genetic African ancestry
44:14that you don't see if you look only at
44:17self reported racial ethnic identity.
44:26And this is another slide that came
44:28from that particular publication
44:30where we're just demonstrating the
44:32genetic admixture of populations
44:34in different parts of the world,
44:36specifically looking at Ghanian patients,
44:38African American patients,
44:40Ethiopian patients and European
44:42ancestry white American patients.
44:44And it's an example of how much more
44:47you can learn about genetics of
44:49disease by drilling down into the.
44:52Genetic ancestry.
44:53And African Americans have tremendous,
44:56tremendous genetic admixture
44:58compared to either Africans
45:01or European ancestry people.
45:03Individuals and you can't rely
45:06upon self reported ancestry.
45:08There are three individuals in
45:11the European ancestry group.
45:13These are individuals who self
45:15reported as being white,
45:16but they have between 30 and 80%
45:19of African genetic ancestry.
45:20So you definitely misinformation if you rely.
45:24Exclusively upon self reported racial
45:26ethnic identity and there are other
45:29examples of how genetic ancestry
45:31might be correlated with health.
45:34April lipoprotein One is an African
45:36ancestry variant that has been
45:38linked to severity of kidney disease
45:40and we all know that end stage
45:43renal disease is more prevalent
45:45in the African American community.
45:47This particular variant is actually
45:49a variant that was acquired to
45:52develop resistance to the African
45:55sleeping sickness disease.
45:57Also,
45:57our wonderful colleague out in California,
46:00Lauder Fairman has been doing
46:02similar work looking at.
46:04Latin X individuals and Lauda has
46:06demonstrated that extent of genetic
46:09Native American ancestry reduces
46:11the risk of getting breast cancer.
46:14On the other hand,
46:16higher extent of European ancestry
46:17is associated with a higher risk
46:20of getting breast cancer.
46:22Other investigators have been
46:23trying to figure out the germline
46:26genetic ancestral causes of the
46:28BRC a founder mutations and have
46:30been potentially linking some
46:32of those founding mutations to
46:34fertility over the millennia.
46:38So we've of course been very,
46:39very excited about our international
46:41group with respect to these
46:43different research avenues.
46:45But it's also been an incredibly
46:47rewarding experience from the
46:49perspective of being able to invest
46:51in the cancer care resources of the
46:54facilities for our partners work.
46:56And our mission statement is to
46:58reduce the global breast cancer
46:59burden through advances in
47:01research and delivery of care to
47:03diverse populations worldwide.
47:04A few examples of how we've been making
47:07those investments are shown here.
47:08We've been able to establish
47:10immunohistochemistry training programs
47:11so that our colleagues can perform
47:14their own immunohistochemistry on site
47:15and actually characterize the cancers
47:17of the patients that they're treating.
47:20We've established core needle
47:21biopsy training program so that
47:23they can make their diagnosis more
47:25efficiently and accelerated through
47:27the COVID experience is that we've
47:29been able to stay in very close
47:31contact utilizing zoom meetings and
47:34telemedicine tumor board discussions.
47:37And now that our program is headquartered
47:40at Wild Cornell in New York,
47:42we are able to align our International
47:45Studies with the robustly diverse
47:46population of New York and we
47:49have our New York based breast
47:51cancer campuses in Manhattan,
47:53Brooklyn and Queens,
47:55which has tremendous diversity
47:57in those communities.
47:59And a lot of our work today is being done
48:01in conjunction with the Englander
48:03Institute of Precision Medicine.
48:04Whenever I talk about
48:06breast cancer disparities,
48:08I always include these survival rates of 60%,
48:11forty 3% and 20%, which have absolutely
48:13nothing to do with cancer outcomes.
48:16But these are the survival
48:17rates for the first class,
48:18second class and 3rd class
48:20cabin passengers of the Titanic.
48:22And even though my own career in
48:24breast Cancer Research and studying
48:26disparities has been heavily
48:27rooted in trying to understand.
48:29Human biology linked to African ancestry.
48:32We always have to end just the way
48:35we began this discussion with a an
48:38expression of the fact that outcome and
48:41the ability to survive any threat is
48:44going to be related to access to care.
48:47And just as the third place cabin
48:49passengers of the Titanic did not have
48:51equitable access to the lifeboats,
48:52it unfortunately and tragically
48:54remains true that communities of color,
48:57including African Americans, do not have.
49:00Equal access to cancer care,
49:02screening, research opportunities.
49:06And as stated by Doctor Martin Luther King
49:09Junior, of all the forms of inequality,
49:11injustice and health is the most
49:13shocking and inhumane.
49:15We saw this injustice in the
49:17COVID experience.
49:18And as you guys know,
49:19it's been projected that as a
49:22consequence of the COVID shutdown and
49:24its downstream impact on Cancer Research
49:26and cancer screening and treatment,
49:29we're probably going to see an
49:31excess of about 10,000 deaths from
49:33colorectal and breast cancer in the
49:35next 10 years because of the COVID
49:39recession was disproportionately
49:40severe in communities of color.
49:42We really do have to be proactive.
49:45In making sure that we protect
49:48our disadvantaged communities
49:49from experiencing these excess
49:52deaths disproportionately,
49:54we want to get rid of all of
49:55these excess deaths, of course.
49:57But unless we support
49:58our safety net hospitals,
50:00which were disproportionately financially
50:02devastated by the costs of COVID care,
50:05unless we protect our advocacy and
50:07philanthropy groups that provide a
50:10lot of our free screening programs,
50:12and unless we really work with
50:15our hospital leadership.
50:16To make sure that they don't
50:18cut navigation programs,
50:20outreach programs,
50:20when they're trying to balance
50:22their budgets in the wake of
50:25the the COVID experience,
50:26we're going to have an exacerbation
50:28of these types of mortality gaps.
50:31But I am an optimist and I do know
50:33that by working together we are going
50:35to be able to eliminate these these,
50:38these disparities.
50:38And I look forward to strengthening
50:41all of the other partnerships that
50:43are already ongoing and bringing
50:45researchers from different areas
50:47together to to try to conquer these
50:49problems from all different angles.
50:52And in closing,
50:53I just want to thank all of the
50:56wonderful teams that have supported
50:58our research over the years.
51:00And in closing,
51:02I do also want to acknowledge
51:05this phenomenal woman,
51:07my sister Deborah Newman,
51:09who passed away almost a year ago
51:13today from an incredibly aggressive
51:16and virulent inflammatory form of
51:20triple negative breast cancer,
51:23and my sister Debbie,
51:25a Princeton graduate, former US prosecutor.
51:29She's a perfect example of how
51:32socioeconomics
51:33are not the exclusive explanation
51:36for breast cancer disparities.
51:38And so it's an in her memory that I
51:41and my research team continue the
51:43the work that we've been doing so.
51:46I do thank all of you for your time
51:48and attention and for inviting
51:49me to deliver this presentation.
52:00Thank you so much Doctor Newman
52:03for sharing your extraordinary
52:05research with our group.
52:07I'd be happy to start with any questions
52:09from the audience before we turn
52:10to the zoom chat.
52:13Go ahead and.
52:18One point. Really.
52:22Was how the self reporting of race
52:28definitely does not usually capture
52:30release what the person is and
52:33that really has me thinking about
52:35populations might be able to look
52:37at these sort of studies that we are
52:40segregating typically but people
52:41said decreased sequencing cost and
52:44ease of access to that sort of data.
52:47Do you and your group's plan on
52:49looking at those populations and
52:51identifying specific genetic factors.
52:52And if you're not ready,
52:53you seen whether a specific
52:55rates have dominance.
53:02Thanks so much for the kind comment and
53:04I totally agree with your points that
53:07we definitely have an obligation to
53:09look more closely at genetic admixture.
53:11And you're right, self reported race.
53:13I mean it's really primitive.
53:14And as cancer researchers we've been
53:17so late to bring the technology of
53:21quantification of ancestry into our work,
53:25but the general population has
53:26been doing this for years.
53:28I mean millions of people are purchasing
53:30these products or they've spent in a cup.
53:32And get back their pie diagram of
53:34where their ancestors are come from.
53:36So I mean I think that this type of
53:38work should be routine in our studies
53:41because we do have the technology and
53:44it's so much more precise and meaningful.
53:47I I agree with you in trying
53:49to understand cancer outcomes.
53:51Now we do need to look at self
53:53reported race as well because a self
53:56reported identity does have very,
53:58very important relationships
54:00to HealthEquity and.
54:03Services that are available to
54:04some communities and not available
54:06to other communities,
54:07but we can't overlook
54:09the genetics components.
54:11So that.
54:13Doctor Weiner.
54:19OK. So Lisa, thanks for a great
54:23talk and sorry about your sister
54:26and thanks for sharing that.
54:28I want to go down a little
54:31bit on ERP project.
54:33And of course adherence to therapy,
54:37Fabian issue, not only adherence
54:40but doctors prescribing entering
54:43therapy which isn't really adherence
54:46which you think of as a patient
54:48issue but maybe a doctor issue.
54:51But the the other question with the
54:54question I have is to what extent
54:58do we know whether simple things
55:00like ER expression vary across race?
55:03Or whether monumental air
55:06versus B percentages bearing.
55:09Yeah, it well terrific questions.
55:13Now from our biorepository,
55:15we definitely see higher frequencies
55:18of those weekly positive ER tumors 1
55:21to 9% in the African ancestry patients
55:24compared to the the white patients.
55:27I can't say that I've seen that
55:30broadly in publications however,
55:32because we usually just talk about
55:35your positive or negative using the
55:37ASCO CAP guidelines, but in our.
55:40Database, we do see that.
55:42So I do think that it's a
55:44spectrum that's present.
55:45I I think you're probably right that
55:48there are variations in how endocrine
55:51therapies are prescribed and how
55:53much attention we pay as healthcare
55:56providers to adherence to treatment
55:58based upon what our patients look like.
56:01I think those are very real issues.
56:03I am so excited that people like you,
56:07the leaders in the clinical trials
56:10are paying attention to this.
56:12In looking at these, these,
56:13these gene expression profiles,
56:15they're going to be I think,
56:16incredibly powerful in studies to come.
56:25Presentation of the body of
56:27work that features beautifully.
56:29Molecular epidemiology,
56:31clinical functions and what
56:34you've highlighted cultural.
56:37I think you have devoted a lot of time.
56:39If I take the same discussion
56:41interest cancer in TCG,
56:43I'll tell you there are five
56:46patients of African argument.
56:47And and that's the disconnect
56:49that I'm always struck with,
56:50you know so much that threat that
56:53biologic androgenicity matters and
56:55clinicians have always been able
56:57to people like we've been able
56:59to answer fundamental questions.
57:01Yet my worry is in our passion to and
57:04you track the time article right?
57:06And I've seen the same thing,
57:08that in our desire to be equal,
57:11we're perhaps missing on those.
57:14Essential things you pointed out,
57:16how do we teach that Vern
57:19academic organization?
57:20And you have highlighted how clinicians
57:23can interact with basic scientists.
57:25How do we as leaders make sure we're
57:28pointing that out to the next generation?
57:31I
57:32would question and it's something that
57:35we all have to keep working on overtime.
57:40I I again I am very optimistic the fact that.
57:46People are documenting cancer outcomes.
57:51Stratified by racial ethnic identity,
57:53where it wasn't necessarily
57:55documented in the past,
57:57the fact that there's a very,
57:59there's a lot of momentum to look at
58:01the the diversity of our workforce and
58:04to develop pipeline programs when very
58:07little attention was paid for the to
58:09this in the past people would remark
58:11upon the lack of a workforce diversity,
58:14but everybody said well,
58:15this is a problem that no group can address
58:18overnight and so nobody tried to do anything.
58:21To address it,
58:22but I think that's the the COVID experience,
58:25horrific as it was,
58:27the COVID experience with disparities
58:29and COVID outcome hitting us
58:32literally in the face,
58:34coupled with witnessing the
58:36horrific murders of George Floyd,
58:39Brianna Taylor, so many others
58:40in the hands of law enforcement,
58:42all of those events happening.
58:45Together made this an extremely
58:47unique moment in time.
58:49And so I think that the efforts
58:51that we're seeing now in achieving
58:52HealthEquity are are real and I
58:54think that it's going to make a
58:56difference and accelerate the
58:57pace of disparities research and.
59:01Accelerate the pace of trying
59:03to achieve HealthEquity.
59:06Breast cancer sort of luminaries
59:07in the in the room right now in the
59:10breast, their breast goes other.
59:14Will have no. Problems giving
59:17their splits the life opportunity.
59:22Ravens. Give patients the audience.
59:26People come. Retesting.
59:27And Antonio Wolf and a bunch of us wrote an
59:30editorial saying that was a horrible idea.
59:33That about any guide?
59:34So people are willing to give their data
59:36yet if they come in for an IRB file,
59:39they're going to make them really
59:41hard and so accurately that makes it
59:43very hard for people to people happen.
59:46And we put so many barriers
59:47into look at clinical trials,
59:49it's really hard for people to limited means
59:52to come to Cornell or to come to New Haven.
59:56So how do we change that because who has
59:59the best interest in understanding that
01:00:01patients and yet we make it so complicated.
01:00:05Urge all of us to sort of think about how
01:00:08do we break those barriers to make this,
01:00:10because it's fundamental.
01:00:11As you said, this was an evolutionary
01:00:15mechanism to survive in Africa, right?
01:00:17Malaria is endemic.
01:00:18And now we're seeing like it makes
01:00:21your hemocyanin your inflammatory.
01:00:23You have this response,
01:00:24but you know, it's the flip side and.
01:00:27So I think that there's a peace for us
01:00:29as as leaders of the field to say what
01:00:32are the are we making researches too
01:00:34complex and simple things like my background.
01:00:38Probably affects how I respond to the
01:00:41world was evolutionary and written into
01:00:43our DNA work thousands of years, right?
01:00:45And we're trying to fix that.
01:00:49You are so right. Yeah.
01:00:51And you hit the nail on the head,
01:00:53I think, in talking about how we've
01:00:56inadvertently created barriers to diverse
01:00:58populations contributing to research.
01:01:00You know, many studies show that
01:01:03African American cancer patients
01:01:04are at least if not more likely to
01:01:07participate in clinical trials if they're
01:01:09offered the opportunity to do so.
01:01:11And we've created all these barriers where
01:01:14clinicians are less likely to offer them
01:01:16for a whole host of different reasons,
01:01:18implicit biases.
01:01:20Sometimes it's just.
01:01:23Incidental Mel with well meaning
01:01:25physicians who are worried that they're
01:01:27going to alienate their patients if
01:01:29they offer an African American cancer
01:01:30patient to clinical trial for fear that
01:01:33the patient might think that they're
01:01:34being treated like * **** Guinea pig.
01:01:36But we have to get over those types
01:01:38of things and we have to offer all
01:01:40treatment opportunities to all of our
01:01:42patients even when it comes to our IRB's.
01:01:44You know we have all these regulations
01:01:47that try to protect people against
01:01:49coercion and so we don't want to
01:01:52offer a financial incentives.
01:01:53Patients for fear of more
01:01:56vulnerable patients being coerced.
01:01:58But our socioeconomically disadvantaged
01:02:00patients need that financial support
01:02:03in order to take the time off work so
01:02:06that they can come in for the visits.
01:02:09So.
01:02:11Such a broad,
01:02:12sweeping problem to try to meaningfully
01:02:14and thoughtfully get rid of some of
01:02:17these barriers that we've inadvertently
01:02:19created and trying to protect our
01:02:22patients against research and justice.
01:02:24The research abuse is, you know,
01:02:26we can't let those come back,
01:02:27but we do also have to be thoughtful and
01:02:29make research easier for our patients.
01:02:35Thank.