Health Disparities

October 05, 2020

Information

October 4, 2020

Yale Cancer Center

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00:00Support for Yale Cancer Answers comes from
00:04AstraZeneca, working to change how cancer
00:07is treated with personalized medicine.
00:10Learn more at astrazeneca-us.com.
00:13Welcome to Yale Cancer
00:15Answers with your host
00:16Doctor Anees Chagpar.
00:18Yale Cancer Answers features the
00:20latest information on cancer care by
00:22welcoming oncologists and specialists
00:23who are on the forefront of the
00:26battle to fight cancer. This week,
00:27it's a conversation about health
00:29disparities in cancer with
00:31doctor Kim Blenman.
00:32Dr. Blenman is an associate research
00:34scientist in medical oncology
00:36at the Yale School of Medicine
00:38where Doctor Chagpar is a
00:40professor of surgical oncology.
00:42Maybe we can start off by you telling
00:45us a little bit more about your research
00:48and what exactly it is that you've been
00:51doing.
00:53I'm an immunologist and clinical chemists with expertise in drug
00:55discovery and clinical development and
00:57in aspects of pathology as you mentioned
01:00I am in the Yale Department of
01:02internal medicine, section of medical
01:04oncology and Yale Cancer Center.
01:06Briefly, I study the immune system of
01:08patients to try to understand how the
01:11immune system is involved in their disease
01:13and their responses to therapy treatments.
01:16I have done research in Melanoma
01:17and I am currently working in breast
01:20cancer as part of the breast medical
01:22oncology translational
01:24research group.
01:26Tell us some of the studies that you've been
01:28doing in breast cancer looking
01:30at the immune system.
01:32Our work is primarily conducted
01:34through clinical trials.
01:35As I mentioned, our goals are to
01:37really try to identify components
01:38or mechanisms of the immune system that
01:41will either help patients to respond
01:43or respond better to therapy or help them
01:46to reduce the therapy.
01:49The way that we do this is
01:52that we look at both genes and proteins
01:56of the immune system and of the tumor
01:58to accomplish our goals we use
02:00many platforms,
02:03research platforms such as next generation
02:05sequencing to identify genes in RNA and DNA.
02:08And we also use Histology to
02:10identify proteins and different
02:12immune and tumor cell types.
02:14And with that being said,
02:19my research is really
02:20interested in looking at many,
02:22mostly biological factors.
02:24As I said,
02:25they are responsible for the disparities
02:27that we have in disease and therapy,
02:30and I am currently working on
02:32triple negative breast cancer.
02:35You noted cancer
02:37accounts for approximately 10
02:39to 15% of all breast cancers.
02:40This subtype of breast
02:42cancer is estrogen receptor
02:44negative progesterone receptor negative,
02:46and HER 2 negative in regards to the
02:49biomarkers that we use to classify the
02:52type of breast cancer
02:53in order to appropriately treat the cancer,
02:56it's often more aggressive,
02:58meaning that it grows and spreads fast,
03:00and so it tends to occur
03:03more often in younger women,
03:05and those were the BRCA gene mutations,
03:08so triple negative breast cancers have
03:10poorer prognosis than other subtypes,
03:12partially because treatment
03:13advances have lagged behind
03:15other breast cancers,
03:16but although treatment options are more
03:18limited than the other breast cancers,
03:21there are still several offices
03:23available to these patients.
03:25And these individuals are treated
03:27with some combinations of surgery,
03:29radiation therapy or chemotherapy.
03:30And right now I'm working on two
03:33clinical studies and one study is
03:35a retrospective evaluation of genes
03:37and proteins from Histology tissue.
03:39From the tumor page,
03:40two more patients with these triple
03:43negative breast cancers to try to
03:45identify immune components or mechanisms
03:47that may be responsible
03:49for the variations that we see in
03:52different racial and ethnic groups
03:54before the patients are treated.
03:56And then the other study is an ongoing
03:58clinical trial that is evaluating
04:00the benefit of giving our triple
04:02negative breast cancer patients
04:04anti PDL one immunotherapy with chemotherapy
04:06before they're taken to surgery.
04:09Those both sound like really
04:12interesting studies and I want to
04:15talk about each one of them in turn.
04:18So the first one, the retrospective study
04:21where you're looking at kind of the immune
04:24factors in these cancers retrospectively.
04:26So these are cancers that have already
04:29been taken out of patients and you're
04:32looking at immune factors in these cancers.
04:35Now I understand that triple
04:37negative cancers perhaps more than
04:39other breast cancers actually
04:40are immunogenic, they tend to have a
04:42lot of infiltrating cells in them,
04:45is that right?
04:46Is that what you're looking at?
04:50or are you looking at other factors as well?
04:53That's absolutely right.
04:54And actually
04:54we're looking at all the
04:56above and
04:57actually we're doing as I said,
05:00looking at different populations
05:02of people within that particular space,
05:04and the reason is because the
05:06percentage of triple negative breast
05:07cancers among the total breast cancers
05:09diagnosed in non Hispanic whites.
05:14Hispanics, American Indians or
05:17Alaska Natives is between 10 and 20%.
05:19I'm sorry 10 to 12% and non
05:22Hispanic Blacks is 21%,
05:24and so we're trying to understand why that
05:27difference exists and more of the biology,
05:29more of the biological questions
05:32and so we're looking at the immune
05:35system to see if there are different
05:38immune players in terms of the amount of
05:41infiltration that we see between these
05:44different populations of people
05:45or the type of inflation.
05:47What type of cells are being
05:50infiltrated in these patients?
05:51And so we're doing that by
05:54looking at the Histology.
05:56Taking the samples of the tumor doing
05:59next generation sequencing on those,
06:02look at the genes and then looking
06:04at different types of immune
06:07cells from the Histology tissue itself,
06:10as well as just using our standard
06:13hematoxylin eosin to look at the
06:17actual global tumor infiltrating lymphocyte
06:20into these populations
06:21sorry into these patients samples.
06:24I want to make sure that I understood
06:26because I mean it sounds like such a cool
06:30project with so much there to unpack.
06:32And maybe you're looking
06:34at all of these questions.
06:35But the first thing that it sounds
06:38like you're doing is really looking at
06:40these cancers to see whether
06:43various immune pathways are turned on
06:45or turned off in the cancer themselves,
06:47whether the they have more or less
06:50infiltration with the immune
06:52system in these cells.
06:54So do you find that there are biologic
06:57differences in triple negative breast
07:00cancer between African Americans,
07:03and say, Caucasians?
07:04And do you think that really
07:07explains why African Americans
07:09tend to have more triple negative
07:12breast cancers than other non
07:15African American races?
07:17So this is one of
07:19the things that we actually are
07:22trying to tease out with this particular
07:25study and all the data is not back yet.
07:27And of course there are other factors as
07:29well that contributes to those differences,
07:32but as I said,
07:34we're really trying to
07:35focus on these differences in the
07:37system that we have seen initially,
07:39and as we're putting more patients on
07:41these studies and look at more things,
07:44we're trying to see if
07:48that gives us any reason to
07:50believe that there are different,
07:53as I said, immune cell populations
07:55that are being introduced that
07:57are different between those two
07:59groups and as well as other groups.
08:02But also if there's maybe a difference
08:05in the amount of those immune
08:07cells that are being introduced,
08:09and so we're still
08:12evaluating the data,
08:13but hopefully that'll give us some
08:15insight if that's indeed true.
08:19Because that would mean that
08:21we may need to
08:24think about how we treat the
08:26patients differently, right?
08:27And it may give you
08:29some insight into potentially why
08:31certain people get triple negative
08:34breast cancers more than others.
08:36Maybe some populations of people
08:38automatically have a more robust immune
08:40response to cancer cells as they are
08:43initially beginning such that they
08:45don't develop into full blown tumors,
08:47and so you may be able to see differences.
08:53Are you looking also at the immune
08:55factors versus stage at presentation?
08:58Because that too might play
09:00into that whole story, right?
09:02Correct, and so
09:04we're looking at
09:06that as well.
09:14That could definitely play a difference
09:16in what makeup looks
09:19like at the end of the day?
09:21Because we want to make sure
09:24that we are comparing
09:26apples to apples.
09:30And so for this part of the study,
09:33you're actually looking
09:35at the tumors DNA, right?
09:37You're taking these tumor
09:38sections and doing next generation
09:40sequencing on the tumor and the micro
09:43environment surrounding the tumor,
09:45has anybody really looked at the immune
09:47system of different racial groups to
09:50see whether there are differences
09:52in immune cell production between
09:55different races that might
09:58give you some insight into
10:00how people mount immune responses.
10:02Whether that's the same for everybody,
10:04or whether there are nuances
10:05and so actually we
10:07have some
10:09evidence to that.
10:12As you think about things like autoimmune diseases
10:14autoimmune diseases tend to be
10:16more prevalent in certain
10:18populations,
10:23and they tend to have as you
10:25look at the immune system,
10:27the immune systems tends
10:28to be very overactive,
10:29and so these are things that can
10:31give us clues that maybe
10:34in different populations
10:35we may need to think differently
10:37about how we approach this,
10:39and so there are studies that have
10:40been done in different fields,
10:42and I think that we can utilize that
10:44to try to
10:46understand how this is applicable to
10:49cancer as well,
10:50and this is actually one of
10:52the main goals of this
10:53particular
10:54study that we're doing is to
10:56try to tease that out as well,
10:58and hopefully we can expand on that
11:00in terms of digging a bit
11:02more deeper into them,
11:03these different
11:05patient populations.
11:05So what I'd like to
11:07look at,
11:09although this particular site is looking at,
11:11individuals of African descent,
11:12individuals of Caucasian descent,
11:13I would also like to expand
11:15that to individuals of Asian
11:17descent as well and
11:18other populations because
11:20I believe that that's actually very
11:22important for us to be represented
11:24in order for
11:26us to understand exactly what's
11:28going on with cancers globally.
11:31And the other thing that
11:33you had mentioned just in passing was
11:36looking at different types of immune cells,
11:38so we often
11:40when we've been on this show,
11:42have talked about these
11:44tumor infiltrating lymphocytes.
11:45And we talk about T cells,
11:47but there are other immune factors
11:50and other immune cells as well.
11:52Do we have any sense of
11:54how these immune cells vary in
11:57terms of their response to tumors?
12:00Either different types of
12:01tumors or to the same tumor,
12:03but in different people?
12:05Actually that's a really
12:07great question, and I've done some
12:09work in this in breast cancer itself,
12:12and so I'd like to share a little
12:14bit about a study that was recently
12:17published looking at breast
12:19cancers in predicting disease.
12:21I'm sorry B cells in predicting
12:23disease free survival in breast
12:25cancer patients and just as
12:27a little bit of background,
12:28metastasis is a frequent
12:31early event in many cancers,
12:32and so in breast cancer,
12:34lymph node invasion is a key determinant in
12:36prognosis and treatment.
12:38So our previous studies have shown
12:40that T cells and injured cells in the
12:42tumor draining lymph nodes may be
12:44altered in some breast cancer patients
12:46and can predict clinical outcome.
12:48But B cells are another major immune
12:50cell population for their role
12:52in solid cancers and is not well studied.
12:55So B cells isolated from
12:57tumor draining lymph nodes,
12:58specifically Sentinel lymph nodes,
13:00which are the first set of lymph nodes
13:02that the tumor drains into
13:04can recognize cancer associated
13:05antigens and are capable of producing
13:08antibodies against those antigens,
13:10and so in our study that
13:12we recently published
13:13we looked at the cells,
13:15and since all lymph nodes in
13:18breast cancer patients,
13:19we found that patients with higher
13:21numbers of these had longer
13:23disease free survival overall as
13:25well as in those patients with
13:28triple negative breast cancer
13:29that had actually good prognosis.
13:32Interestingly this can
13:34be seen in Melanoma patients and we
13:36recently also published this and
13:39we have found higher numbers
13:41correspond
13:43to longer progression free survival
13:45in patients with metastatic Melanoma
13:47treated with anti PDL1 immunotherapy.
13:51And so have we found a difference in
13:54terms of the number of B cells that are
13:57in tumors of people of African American
14:01descent versus Caucasians. So this
14:03is one of the things that we're
14:06looking at and that
14:09data is still to be evaluated.
14:11Certainly,
14:13if it's true that B cells do
14:16predict differences in survival,
14:17it sounds like it is a relatively
14:20simple prognostic factor.
14:25And it could give people an idea of
14:27how this biology is going to play out,
14:30particularly as it interfaces with
14:32the immune system.
14:34You're absolutely right, and
14:36the other thing that I'd like to
14:38point out too is that
14:40the immune system is called a
14:42system for a very specific reason.
14:44It works as a system,
14:45so B cells do not work in isolation.
14:47T cells do not work in isolation,
14:49and so all these things require
14:53to be working together
14:55and so this is one of the things
14:57that we need to think about when we
15:00make these prognostics and predict
15:02the tools is to consider all
15:04these different immune systems
15:05and put them together to make
15:07choices that we move forward.
15:09We're going to pick up on
15:12that conversation right after we take
15:13a short break for medical minute.
15:15Please stay tuned to learn more about
15:18health disparities and cancer and the
15:20immune system with my guest doctor Kim Blenman.
15:22Support comes from AstraZeneca,
15:24working side by side with
15:27leading scientists to better
15:29understand how complex data can be
15:34converted into
15:35innovative treatments. More information at astrazeneca-us.com.
15:38This is a medical minute
15:40about colorectal cancer.
15:42When detected early,
15:43colorectal cancer is easily treated
15:45and highly curable and as a result,
15:48it's recommended that men and women
15:50over the age of 50 have regular
15:53colonoscopies to screen for the disease.
15:56Tumor gene analysis has helped improve
15:58management of colorectal cancer
16:00by identifying the patients most
16:02likely to benefit from chemotherapy
16:04and newer targeted agents,
16:05resulting in more patient
16:07specific treatments.
16:08More information is available
16:10at yalecancercenter.org.
16:11You're listening to Connecticut public radio.
16:16Welcome
16:16back to Yale Cancer Answers.
16:18This is doctor Anees Chagpar and I'm
16:21joined tonight by my guest doctor Kim Blenman
16:25and we're talking about health disparities
16:27in cancer and right before the break
16:30Kim, you were talking to us
16:32about some of the studies that
16:35you're doing in breast cancer,
16:37and specifically one study in triple
16:39negative breast cancers where you're
16:42looking retrospectively at the
16:43various immune systems and immune
16:46responses that are mounted by patients
16:48with triple negative breast cancer and
16:51you kind of left us hanging
16:54in terms of the details of whether this
16:58is really different between African
17:01Americans and Caucasian patients.
17:03We know, for example,
17:04that in triple negative breast cancer
17:07it seems to be more prevalent in African
17:10Americans than in Caucasian patients.
17:13Can you shed some more light on how
17:16different cancers affect different
17:18racial groups differently?
17:21Yes, and as I mentioned,
17:24my research interest is in the
17:26biological factors responsible for
17:28disparities and disease and their responses.
17:31So in that context,
17:33Melanoma is a great example.
17:35So Melanoma is a skin cancer that
17:38occurs most commonly when the DNA in
17:40melanocytes is damaged by UV rays.
17:43That is sun exposure.
17:44So melanocytes are the
17:46cells that produce melanin,
17:48which gives skin its color.
17:51Eumelanin is a type of melanin that
17:54is responsible for darkening the skin
17:56and it has the ability to protect the
18:00skin from UV damage so when individuals
18:03tan as a result of exposure to the sun,
18:06youe melanin is responsible for the
18:09visible color that you see as the tan so
18:12individuals with naturally darker skin,
18:15have more eumelanin and are therefore
18:17at lower risk for developing
18:19UV induced skin cancer.
18:22So for decades,
18:23the messages that were shared in general
18:26and in communities of people of color
18:29with naturally darker skin was that
18:31people of color do not get Melanoma.
18:34However,
18:34today we know that the most common form
18:37of Melanoma found in individuals with
18:39naturally darker skin is acral Melanoma,
18:42which is often found under nails.
18:46On the palms of hands and the soles of feet,
18:49and disease of face.
18:52The musician Bob Marley from
18:54Jamaica died of acral Melanoma.
18:55And so this is a good
18:58example of why it's
19:01important that we actually take into
19:03account these biological factors and
19:05try to find or look for things that
19:08may give us some clues as to why
19:12things are different that are not
19:15a part of social determinants of Health
19:17and so this is how we really got
19:20interested in looking into these
19:25different factors for
19:26these different cancers.
19:28That makes sense in in Melanoma,
19:31in breast cancer we were
19:34talking about before the break
19:36it's a little bit more
19:38tricky in the sense that there doesn't
19:41seem to be a particular factor.
19:44Something like eumelanin,
19:45which would be different between African
19:48Americans and Caucasian patients,
19:50which I guess is how you
19:52got into thinking about
19:55why is it that triple negative
19:58breast cancer is more common in
20:01African American patients
20:03and could this have something
20:06to do with their immune system?
20:09Because certainly we know that triple
20:12negative breast cancers are immunogenic.
20:16Exactly, and actually,
20:16that's the link with
20:18the acral Melanoma as well.
20:19So the thing about acral
20:21Melanoma is that it actually has a
20:23lot of infiltrating immune cells.
20:25and are a little bit less
20:28involved in individuals of Caucasian descent,
20:30and so
20:32you're thinking about, okay
20:34let's look at the immune cells.
20:36You know there's something
20:37different about the immune cells.
20:39and the types of cells also infiltrated
20:41that's making these differences that we see.
20:45And I suppose you did
20:48mention before the break about
20:50your study looking at B cells,
20:52and I believe you mentioned that you
20:54found that B cells were tied to prognosis
20:57in both Melanoma and in breast cancer,
21:00correct?
21:03I guess that leads us to the next study
21:07that you had mentioned before the break,
21:10which is a prospective trial
21:12looking at immunotherapy because,
21:14as we've talked about on the show previously,
21:18and as many of our listeners may know,
21:21immunotherapy actually has
21:23really taken hold in Melanoma
21:25and is just starting to get evaluated
21:28in breast cancer and specifically in
21:31triple negative breast cancer, so
21:33maybe you can tell us a little
21:34bit more about your work there.
21:40In the last five to 10 years or so
21:42you've mentioned,
21:44we've started to really recognize
21:45that the immune system has a role in
21:47how cancer patients will respond to
21:49many of the therapies that we give,
21:51including chemotherapy.
21:52So to take advantage of that fact,
21:54we are, as you mentioned,
21:55starting to identify and use therapies
21:57that directly impact the immune system
21:59alone or in combination with chemotherapy.
22:01So, for example,
22:01we have an ongoing study that
22:04is evaluating the benefit of giving our
22:06triple negative breast cancer patients
22:08Anti PDL1 immunotherapy with
22:10chemotherapy before they're taken
22:12to surgery and the advantage of that
22:15is that we're trying to understand
22:17whether or not this
22:20particular regiment of giving that
22:22immunotherapy could help boost
22:24the immune system's ability to
22:27see the cancer or to break it down
22:29so that the chemotherapy itself
22:31can respond better to the cancer.
22:33And, as I said,
22:35the study is still ongoing,
22:37but we are starting to see some
22:40very interesting results that
22:41have some positive benefit
22:44for Anti PDL1.
22:47Now how does
22:49that immunotherapy work,
22:51particularly for people who
22:53have PD L1 or PDL or PD one
22:58receptors or would it work
23:00for any triple negative?
23:02Actually this is
23:05kind of interesting because we're
23:07actually finding that we are getting
23:10affected regardless of whether or
23:12not the individuals have PD L1
23:15as part of their tumor,
23:17and so there are other things
23:19going on there that are mediating
23:21this response that we're still trying
23:24to learn for this particular PD1
23:26PD L1 Axis.
23:29So it's certainly a really interesting
23:31and novel thing to think about,
23:34and I know many of our listeners are
23:37always intrigued by immunotherapy.
23:39It seems to be a really hot topic,
23:43but when we think about immunotherapy,
23:45one of the things that we always caution
23:49patients about is the side effects,
23:51which tend to be
23:54side effects that are an exacerbation of
23:58the immune system because essentially you
24:01rev up your immune system or as you say,
24:05you can make tumor cells more
24:08susceptible to the immune system,
24:10now have you noticed a difference
24:13in terms of racial groups with
24:16regards to those side effects?
24:19Because you mentioned that there
24:21is a racial difference in terms
24:24of autoimmune diseases so
24:26one would imagine that there might
24:28be a difference in terms of the side
24:31effects with immunotherapy as well.
24:33Have you found
24:34that so?
24:37That's a great question and something that
24:38we are actually evaluating now.
24:40And so as I said,
24:42the study is still ongoing,
24:44so we don't have enough patients
24:46collected yet in the different groups
24:48to actually make any statements.
24:51But this is actually something
24:52that I am very interested in.
24:55And is one of my
24:57major goals of this study is
24:59to try to tease out NOTE Confidence: 0.89420384
25:02those potential differences that we see
25:04between different populations of people,
25:06but no, we don't
25:08have that information yet,
25:11but I suspect that we will be able to
25:14see in these studies and other studies
25:17that others are doing.
25:18Do we know whether different
25:20racial groups will respond
25:22differently to immunotherapy?
25:23For example, if patients have a
25:26similar tumor in terms of their PDL1
25:29status. The size of the tumor,
25:32the B cells and the T cells that
25:35are in the micro environment and
25:38you give them immunotherapy.
25:41Do we know whether,
25:42just by fact of different racial groups,
25:46they will Mount a different immune
25:48response that will then result in
25:51differences in terms of the effect?
25:56So I think one of the first things
25:59that we need to think about is
26:02the individual and
26:05for that purpose you know
26:07the health of the individuals is
26:09influenced by many interconnected
26:11factors such as their individual biology,
26:13their behavior,
26:14environmental and physical influences.
26:16The type of medical care that they're
26:19getting and the social determinants
26:20which are influenced by both the
26:23socio economic and political factors.
26:25And so we now know that each of
26:27these factors can lead to the health
26:30disparities that exist in cancer,
26:32and so these are the things that we
26:35actually need to consider when we
26:37talk about potentially,
26:39one population being
26:41different than the other,
26:43and so I think the individual health is
26:46something that we should
26:50consider versus the entire population
26:53of that individual.
26:55So with that being said,
26:58it's going to be determinant on what
27:00their biology is that individual
27:02biology and how they are going
27:04to respond to that individual therapy,
27:06and so I don't want to generalize to an
27:08entire population on that perspective,
27:10but I think you know the more
27:13pressing question for me is,
27:15how can we overcome these
27:17disparities that I just mentioned and for
27:19me I think that we need to
27:23do more inclusive research.
27:25We need to recognize that as human
27:27beings we are part of a collective that
27:29is made up of different populations.
27:31And then in order for us to move
27:33forward in science and medicine,
27:35we need to include all of our populations
27:37in all of our research endeavors.
27:39And this level of diversity is not only
27:41required in the populations that we study,
27:44but it also needs to be equally represented
27:46in the faculty members that are
27:47performing and or involved in these studies.
27:50So again, representing the diversity
27:51of our global population.
27:52But again,
27:54giving us some concept of the
27:55individual as well.
27:57Doctor Kim Blenman
27:58is an associate research
28:00scientist in medical oncology
28:01at the Yale School of Medicine.
28:04If you have questions,
28:05the address is canceranswers@yale.edu
28:07and past editions of the program
28:09are available in audio and written
28:11form at Yalecancercenter.org.
28:12We hope you'll join us next week to
28:15learn more about the fight against
28:17cancer here on Connecticut public radio.