Oncologic Anthropology: African Ancestry and TNBC

Transcript

• 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.