NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION

NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities

April 27, 2012 Contents

Breakfast Symposium – supported by Medco...... 1 Breakfast Symposium – supported by Medco

[START NHMA_BREAKFAST_SYMPOSIUM]

FEMALE VOICE 1: It is important for us to start on time because many of you have signed up for the congressional hearing and the bus will leave at 9:00 at our front doors. We want to be done by that time. Just a little plug for the National Hispanic Medical Association, those of you that were here yesterday and went to the White House briefing had a wonderful experience, you understand how important our organization is in the national level, in that we are the voice of these Hispanolatino population of health care workers. I would urge all of you that have not joined the organization to please fill in your paperwork and pay your dues and join the organization.

When you become a member of the National Hispanic Medical Association, you have opportunities to serve on various boards and these boards may be of any topic of interest. Some are political. Some are healthcare. There’s just quite a variety. Some are paid. Some are volunteer, opportunities to travel, opportunities to learn, to meet many people at the national level.

Today, we have a wonderful breakfast topic. I think it’s going to be well worth having gotten up and being here to hear this talk. We’re going to talk about personalized care in the Hispanic population. We have two speakers.

Our first speaker is Dr. Milayna Subar. She is an internist who did her residency in Albert Einstein College of Medicine and is board certified in hematology and medical oncology. She currently is with Medco, which is now Express Scripts and has the role of National Practice Leader for the Oncology Therapeutic Resource Center. In this role, she’s responsible for setting the direction for the Oncology Specialist Pharmacies who are part of the care team for nearly 1 million members receiving drugs for the treatment of cancer or related symptoms.

But today, she’s going to be talking about genetics and genetics of breast cancer and how it relates to the Hispanic population. Join me in welcoming Dr. Subar today.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 1 April 27, 2012 DR. MILAYNA SUBAR: Good morning to everybody who’s here, those who are about to come. I guess people will be coming in over the next little while. Thanks for getting up early to hear me talking about breast cancer.

One of the issues in breast cancer is, of course, that a lot of people don’t like to talk about cancer. There are a lot of families, cultures that just have a sensitivity about talking about cancer. But, if you don’t talk about it, we won’t learn about it.

I wanted to start with the question Are all breast cancers the same? If we’re talking about personalized medicine, particularly in a particular population or in a particular— it’s not really a racial group or racial slash ethnic group, is it all the same?

Let’s start with the big picture. Is all breast cancer the same? All breast cancer isn’t the same. We learned many, many years ago about the estrogen receptor. Now, we know about the HER2 and we have drugs to target HER2. I don’t know if you’re familiar with the terms luminal A, luminal B and basal subtype. But, those are all important subtypes of breast cancer as well. There are two genetic panels that are often used, Oncotype DX more in the US, MammaPrint which is developed in Europe, but is also approved for use in the US, that are tests that use multiple genes to help predict how a breast cancer will behave and to help physicians make decisions about how to treat breast cancer.

I’m not going to talk about all of these, but I wanted to mention them to show you how diverse the picture of breast cancer is. In fact, there was a paper that was just presented—I think it was last week—that identified 10 different subtypes of breast cancer. That’s not put into use at the moment. It’s more of a bit of new research information, but we certainly use at least the estrogen receptor, the HER2 we talk about triple negative, the luminal and the basal subtypes.

We know that breast cancer is all different. But, how about among populations? How does breast cancer behave within populations? This is, of course, a clinical question rather than a personalized medicine question. There are data. This is US data from the American Cancer Society. They publish their data each year and there are

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 2 April 27, 2012 five different populations that they look at, non Hispanic White, African American, Hispanic and the Latino population, American Indian, Alaskan, Native and Asian American Pacific Islander. For this morning, we’re really going to focus on two groups, non Hispanic White population and the Hispanic population.

There are three different categories of data that I wanted to focus on here, the incidence which is, of course, the rate of new breast cancers and the five year survival. The mortality is also different, but that’s more related to these two other factors. If we just focus on those two specific statistics and those two populations, non Hispanic White and the Hispanic Latino population, what’s the takeaway? The takeaway is breast cancer incidence is lower in the Hispanic population. 91 instead of 125 new cases annually per 100,000 population.

There are fewer breast cancers, but five year survival is lower. The five year survival of breast cancer in the Hispanic population is 84 % and in the non Hispanic White population, it’s 89 %. In addition, greater decreases have been reported for incidence in the non Hispanic than in the Hispanic population. There are differences that are very important to understand and to be able to address moving forward.

There has been work published looking at why these differences might occur and differences such as mammogram screening rates or utilization of care. That’s not really what I want to focus on today. What I really to focus on today is the frequency and the impact of individual risk factors and how these vary across populations.

There are two kinds of factors that are important to look at. On the left, you can see the list of risk factors for the development of new breast cancer. These are risk factors that individual women or individual families, depending on what the factor is, carry. Obviously, age is an individual. Family history and what I’ll talk about in a little, which is the breast cancer gene mutations, those are inheritable or inherited. All of these are considered very well defined risk factors for the development of breast cancer among broad populations, just thinking of everyone.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 3 April 27, 2012 I’ll talk a little bit about how that relates specifically to the Hispanic population. Then, there are prognostic factors once someone has already breast cancer. I mentioned the two at the bottom, the Oncotype DX and the MammaPrint. But, the others, which I also mentioned a little—do those differ among different ethnic groups? That’s something that we will look at as I move forward.

Let’s start with the risk factors for breast cancer. You can’t take one risk factor and just look at it in isolation. You can’t say, Well, how old was this woman when her first child was born? It’s really a multiplicity of factors and there are several tools. One is the Gail Score, a few tools that are out there. If you go to the Internet, there is a risk assessment tool for the risk of developing breast cancer that you can access online and what you do is you put in the specific answers to questions. How many children? How old was the woman when she had her first child? And, all of the factors that are listed on that tool are in the second bullet here. Age, menstrual history, reproductive history. The calculator then will weigh these factors and provide a percentage probability of developing invasive breast cancer within the next five years or during one’s lifetime up to the age of 90.

I went in and I said, let me put some information. I tried different—my real data, my fake data, somebody else’s fake data, just to see what kinds of information I would get. When I put it in, and I know this is not easy to read purposely, it’s not highlighted here. But, in the last question, this is an abbreviated form. This are the questions, but not exactly as they appeared, What is the race or ethnicity? If you put in Hispanic, this is what it says. It says, Assessments for Hispanic women are subject to greater uncertainty than those for White and African American women. Researchers are conducting additional studies, including studies with minority populations, to gather more data and to increase the accuracy of the tool for women in these populations.

I, frankly, didn’t think that was very reassuring because it didn’t provide me with an answer. But, I tried to understand that a little bit, a little bit more. I looked up what are the risk factors? What are the studies that

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 4 April 27, 2012 are done to look at risk factors in a population of Hispanic women? I found that there are studies going on. There are several. One is the Four Corners study that’s looking at a population of Hispanic women in four states at the left part of the country. What was found, and I mentioned the different risk factors, age, age at first childbirth, obesity, all of those risk factors. They found that even though in the non Hispanic White population, these are well characterized, they’re not necessarily as impactful in Hispanic women.

The earlier age at first childbirth, having more or fewer children, the use of hormones, those were not really associated with a higher risk of breast cancer in Hispanic women. I thought that was very interesting. Also, obesity was not statistically significant. It was a trend towards more breast cancer in women who were obese, but it did not reach statistical significance in the Hispanic population. I thought that was fascinating because, in fact, obesity is thought to—the effect, also, are thought to contribute to a higher level of estrogens because estrogen hormones are converted to estrogens in adipose tissue.

I thought, maybe, that’s important in understanding the type of breast cancer, not only whether or not someone gets breast cancer. I’ll get back to that in just a minute.

But, one of the other findings was that, in another study, there was an analysis of the epidemiology of the breast cancer gene itself. I’m going to just, as an aside, talk about this gene in a broad sense.

The breast cancer gene, breast cancer BRCA1 and 2, are often mutated in various populations. Women who have a mutation, a harmful mutation in one of these genes, have about five times more likelihood to develop breast cancer than someone who does not have the mutation. Although about 12 % of women in the general population will develop breast cancer during their lifetime, it’s high. It’s about 60 % in the population with the particular mutation. Moreover, when breast cancer does occur in this population, it is more likely to be negative for the estrogen and progesterone receptor as well as the HER2 receptor and have what we call a basal phenotype, which I mentioned at the beginning, when we were talking.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 5 April 27, 2012 It’s important to know about this gene to have testing where appropriate. It doesn’t mean everyone goes out and get testing. You need to talk to genetic counselors and experts in the field. But, if there is a BRCA1 or 2 mutation in a family, it’s important to have counseling for the people in that family.

How common is this mutation in a population of Hispanic women? Well, not only women, because obviously the gene can be active in anyone and, in fact, although it’s not the topic today, there is an increase in prostate cancer in this population as well.

I have a particular interest in it. I’m in the category of Ashkenazi Jews. I’m not in the—in case you did guess—in the category of Hispanic women. But, as you can see, the frequency of or the prevalence of a harmful mutation of BRCA1 is over 8 % in Ashkenazi women. In other non Hispanic White populations, it’s just about 2 %. But, in Hispanics, it’s somewhere in the middle. It’s somewhere in between. It’s higher than I would have expected. I found that very interesting, especially since it was a surprise to me and because, actually if you recall, I said the incidence of breast cancer is not higher in the Hispanic population.

What this means, I don’t know. But, it is something that’s very important to be aware of and to think about if there is a high frequency or a family history of breast cancer. And all family history of breast cancer is not related to this gene, but some is. So, it’s important, as I said, to talk to a genetic counselor.

What is it about the population that makes this important to know about - - and higher than usual? Just to summarize on the risk factors, some of the risk factors for breast cancer that are well characterized in other populations may not be as impactful in Hispanic women. However, the frequency of BRCA1 gene is something to remember. I just said some of the risk factors aren’t as important. For example, obesity is not important, and I suggested that maybe that has a relationship to estrogen impact on the development of breast cancer.

Let’s talk about age [phonetic] risk factors for the outcome of the breast cancer itself. Once a woman has a

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 6 April 27, 2012 diagnosis of breast cancer, what influences how that breast cancer behaves? I mentioned several different, sort of an alphabet soup of breast cancer types. ER positive, PR positive, HER2 positive, all of those different things.

There are some studies looking at the populations and I just really want to point out two among those on this table. The first study is from a California registry using data that was from 1999 to 2005, and this is a large study. There were over 69,000 women in this study altogether, the White non Hispanic, Hispanic and African American. One of the things I think that really is pointed out by this study and is reiterated in the others is that estrogen and progesterone receptor positive breast cancer, which you see here is not quite 50 %, is higher in non Hispanic White women, lowest in African American and somewhere in between in the Hispanic population.

ER positive, PR positive breast cancer is usually a better prognosis. Those women do better. They’re treated with tamoxifen or, in postmenopausal women, they may also be treated with what we call an aromatase inhibitor and they generally do exceedingly well.

But, as you can see, there are fewer in the Hispanic population. Triple negative disease, which is considered a less ideal—if you want to call any breast cancer ideal— subtype and has little targeted therapy currently available is also in between in this population, more than in White non Hispanic and less than in African American. I’ll point out African American women do have a rather poor outcome from breast cancer.

The Hines study, which is the Four Corner study, also had a different incidence, but a lower incidence of estrogen receptor positive than in White non Hispanic. Sometimes, the differences can be attributed to pre and postmenopausal mix. So, there are various other contributing factors. In this particular study, the population that was looked at, even though it was a four state study, for the estrogen receptor it was the women from Colorado who participated. Again, the triple negative had a higher incidence in this population, although it did not reach statistical significance.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 7 April 27, 2012 Now, I’ll point out that there are some studies that don’t necessarily agree with this. In the STEED study, it doesn’t have a circle around it, but it’s the next one down, second from the bottom. You can see that estrogen and progesterone receptor was about the same. Triple negative was about the same. But, when we look at these studies, we have to look at the details of the study. In this particular study, although there were about 415 women in the whole study, only 43 were Hispanic women. From a statistical perspective, it’s hard to appreciate that this may actually carry over into the general population.

Why all these differences? In addition to study size, population varies. We look at the geography in different parts of the country and there are different mixes. I worked in the Bronx and in the Bronx, there is a significant Dominican population, which I don’t think is present in many other Hispanic groups around the country.

I think it’s important to look at that. There was a study by Pinero [phonetic] et al. looking at the breast cancer incidence in different populations, Cuban, Mexican, Puerto Rican and new Latinos. You can see it really is quite variable. So, we have to remember that when we’re looking at this, particularly the genetics of a disease, the population mix is very important.

How are we addressing this? Well, the North American Association of Central Cancer Registries, which is responsible for collecting a lot of the data, including the data that will be translated into what we call the SEER database, which is available publicly on the Internet, has developed a tool, an algorithm to be used by cancer registries to help determine how to classify patients within the cancer registry, when they’re looking at ethnicity. That is one thing that I think is important and useful. It’s useful not only because we want accurate data, but we want accurate data to translate into that breast cancer predictor model that I talked about in the beginning where the - - said, Predictions in the Hispanic women are less accurate because we don’t have enough data. So, I said, Well, how much data is there really out there? I tried to identify the population mix in some of the studies and I found that trastuzumab, which you may know as Herceptin, which targets the HER2 marker in breast cancer,

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 8 April 27, 2012 one of the markers I talked about already. The pivotal trial for that particular drug had only 5 % of the population being Hispanic. That’s not very high and if we have 12 % of all women with breast cancer being HER2 positive and it varies from study to study, then it’s not trivial. 5 % is, I think, very small.

We need to increase the representation in clinical trials. I’m looking at the National Cancer database hospitals, which are those that are often included in some of the SEER database, it’s also only 4 %. I think the algorithm that I just mentioned may help to increase that if women can be identified with an ethnic group that they are, in fact, part of.

The Oncotype DX, which is a - - diagnostic test, although it’s used also to determine whether or not a woman needs chemotherapy or not. Only 14 % of the women were Hispanic. I think it’s important to increase the representation in trials, so that we can actually understand better both how the disease behaves, what the risk factors are and the intricate details of breast cancer in the Hispanic population.

Now, I don’t want to end without just coming back to basics. I started talking about the different types of breast cancer overall more broadly. I talked about patients subgroups and I talked about the fact that even though the incidence of breast cancer is lower, the survival rate is also lower and we need to look at reasons why. I indicated that one of the reasons may be that there are less fewer women with estrogen receptor positive disease.

There are more women with triple negative disease. But, having said that, I don’t want to forget the fact that access to care, once someone has a diagnosis of breast cancer, is also important. I just wanted to close with a mention of something called a Patient Navigator. There is a Patient Navigator tool that is available and there are Patient Navigators who are individuals who help patients. It’s an intricate system. I don’t know if anyone in the audience has had cancer or has a loved one who had cancer. It’s not an easy process to navigate. There are Patient Navigators and this data is specifically from a Hispanic

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 9 April 27, 2012 population, improved intervention, the timeliness of intervention, the diagnostic resolution which involves all of these genetic tests, estrogen, HER2, potentially luminal A or Oncotype DX. So, getting answers, getting those tests done, getting the answer, adherence to the follow up appointments, and shorter time to diagnosis. All of these are improved with a Patient Navigator.

I think that is one of the additional takeaways. Each individual patient is needing personalized care and some of that personalization is in the genetics and some is how we actually treat the individual patient and we have to really bring that together to get the best outcome for the patients with breast cancer.

I think we’re going to take questions at the end.

FEMALE VOICE 1: Well, I actually changed my mind because I think the topics are going to be so diverse that it would be really great to just have you answer questions right away.

DR. SUBAR: Okay.

FEMALE VOICE 1: I would like to know if there are any questions for Dr. Subar. Chris, come to the microphone.

CHRIS: I just wanted to ask I believe I was at a conference called Latinas - - Cancer. I think it was a year ago. On a lecture of genetics and breast cancer, I believe—and my memory might be wrong—but I believe that one of the lecturers--and I’m sorry, I don’t remember her name—said something about they were finding that the gene alleles similar to what was in the Ashkenazi Jews was being found in—I think she said Southern Mexican women or in Latinas and that they were finding that there was the same gene there. And, I don’t think you said it, but I just want to clarify if that’s true.

DR. SUBAR: The study that I mentioned is really more broad. I think that there is more data that showed that the ethnic mix, in terms of background and what population people originally came from, where in Europe for example, varies greatly. And so, there is variation among the different Hispanic populations state to state, region to region where people came from and what their specific background is,

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 10 April 27, 2012 their family background, where their families came from and the genetic mix. So, I don’t know the specific variation of BRCA1 in Hispanic women around the country, but what you’re saying is fully consistent with what I’ve seen.

FEMALE VOICE 1: What I would say from being from the Hispanic Southwest in Colorado and northern New Mexico, there’s a high incidence of this mutation. If you practice there, it’s very important to be sending these people to genetic counselors.

DR. LUIS ESTEVEZ: Excuse me. Good morning. I’m Luis Estevez from New York. Thank you for that excellent talk. There’s been a proliferation of tests that test for different genes and there’s not been a good way to validate a lot of the accuracy of these tests. Everybody has their own formula. How accurate—or, what tests have you used that you can tell us that have been used in White populations that are accurate? Is this a real problem?

DR. SUBAR: It is. It is a problem and I think what you have to think about when you think about a genetic test is what I call clinical utility, and clinical utility has several different aspects to think about. One is Is the test itself a valid test? Does the laboratory have reproducibility? Do the test over and over to reproduce the same test. That’s very important to me to have the right lab do it. Does it influence decision making? There are many tests that don’t influence. They’re interesting. You can test whether your metabolism of caffeine is fast or slow. I would venture to say that most of the people know if they are sensitive to caffeine or not. But, you could do a test to find that out. But, I don’t know if it will make an impact on your medical care.

I think that it’s really looking at all of those characteristics of a test. Now, in breast cancer, the ones that I mentioned, estrogen receptor, HER2, Oncotype DX or MammaPrint, you don’t have to do both, are all validated tests. Now, HER2, there has been data. It’s a few years old because I think the testing has improved a lot. There was data showing that variability between laboratories and some labs had a less reliable procedure for testing. But, it’s become much more reliable. There are some new cancer drugs.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 11 April 27, 2012 In addition to Herceptin, there’s one that also targets HER2 that’s under review right now. There’s a lung cancer drug that need a test called ALK. There’s KRAS. There’s a bunch of cancer genes that influence the use of specific drugs. Often, these are not inherited, but they’re in the cancer itself. When it’s a test that influences whether a drug will work or will not work, that’s very important. Those are very valid.

When there are tests that influence whether you need more intense screening for breast cancer. For example, if you have BRCA1, we didn’t go into treatment, but there are women who have prophylactic mastectomies, which is obviously something you have to discuss and not something you just go out and say, Oh, do it.

There are women who have screenings every 6 months, instead of every 12 months. Anything that influences the treatment or the prevention of a disease is very important. If it’s something that’s not going to influence a decision, it’s still investigational, I think participating in studies of how important these genes are is important, but doing them on a routine basis is not generally recommended.

DR. ESTEVEZ: Thank you.

FEMALE VOICE 1: Are there any other questions?

DR. JOSE ROJAS: Hi, I’m Jose Rojas from New Jersey. Thank you for your presentation. Your presentation, it seemed like it lacked a lot of data from a Latino perspective. I was just wondering whether or not you find that there may be some type cultural barrier or some type of modesty or shameness to come forward to be tested and what have not. Or, is there a financial barrier where insurers don’t pay for such testing. Or, have you found that maybe physicians, for the most part, providers for the most part, are not really truly educating the patient as to why the importance of going forth for testing?

DR. SUBAR: That’s a very important question. For BRCA1, I think that there’s an awareness issue. I think that people didn’t really think of it as important in Latinas as much as it’s important, for example, in Ashkenazi Jews. I think it’s something people should be aware of. In terms of testing for estrogen and HER2, estrogen receptors should—

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 12 April 27, 2012 everybody who has breast cancer should have that tested. I’m pretty sure that is routinely done.

HER2 is not as routinely done. There are some studies showing that there was less of an application of HER2 testing in both Hispanic women and African American women. However, let me just point out that the data that I reported, basically, go through 2005 and 2006 and we’re now in 2012.

Herceptin is a drug that is used to breast cancer that is HER2 positive. You really should have testing before you use the drug. But, it’s not been around that long. What I’d really be interested in seeing, and I haven’t seen it, but I’d be interested in seeing more recent data. Really, what is coming out, what’s being done today, rather than what was published from registries through 2006. There may be a difference in approach. I think that one of the reasons I mentioned the Patient Navigator because I think that type of project can bring people along to get the best care that they should be getting. But, I also want to see more recent data on the testing.

FEMALE VOICE 1: Any other questions? Well, thank you so much, Dr. Subar.

DR. SUBAR: Thank you.

FEMALE VOICE 1: Our next speaker is Dr. Jorge Quel and he is the Director of the Hispanic American Allergy, Asthma and Immunology Association, and also the Director of the Allergy Asthma Sinus Center in Marina del Rey, California. He is a consultant for UCLA Santa Monica Hospital, Marina del Rey Hospital, Brotman Hospital and a preceptor for Western University Medical School, President of the UNAASMA, which is the International Olympic Games for the Patients with Asthma and he’s going to be talking about the genetics of asthma. Dr. Quel.

DR. JORGE QUEL: Thank you. Good morning. I would like first to thank you, the members of the board and, especially, Dr. Elena Rios for the invitation to participate in this symposium.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 13 April 27, 2012 I am going to discuss asthma, a disease in the Spanish population and related, of course, to the personalized medicine.

The definition of personalized medicine, which probably everyone is doing, is trying to - - genetic biology information, understand the requirements for optimal care, health maintenance and disease prevention.

Having an increase in the rise and incidence of a non communicable disease, we are not the increase of Crohn’s disease, multiple sclerosis, diabetes type I and asthma.

There are several factors that are very important to understand the asthma morbidity, the genes, the environmental factors, cigarette smoke, air pollution, exposure to the allergens, exposure to stress and violence, time of exposures. The change in the microbial flora and I’m talking about the intestinal flora that you can see just in the newborn. Parasite exposure, diet, obesity, race, ethnicity, sex, migration and acculturations.

When we see the difference between frequency in asthma under the age of 17, we see a significant difference between the different population of Hispanics. Hispanics mix, which we have the different groups than the highest one is the Puerto Ricans. Follow up by the African Americans, Cuban, White and the last in frequency are the Mexicans.

When we analyzed the data over the age of 17, we still have the same proportions. Puerto Ricans are the highest incidence of asthma and mortality and morbidity in the Spanish population. The same is a little lower in the Mexicans.

We’re talking about genetics. We started in 2001 with the Malfin [phonetic] in which we are interested in the variation as explained in the single nucleotide polymorphism, SNP. In 2005, we have the Hepma [phonetic] Project, which have significant difference between Asians, African Americans, Whites and Hispanics.

The revolution we have in genetic, having come in more like with the GWAS and the Gee whiz. What is a GWAS? It’s a genome wide association studies, which we follow up a

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 14 April 27, 2012 disease according with the genetics. But, recently, in the last few years, it starts with the Gee whiz, and we are put in the environment out and the relationship with the gene are becoming so important.

This is how the GWAS stands and is increasing the reduction of costs and with the new chips, it’s fantastic increase in the frequency that we can do. We have so many asthma allergy genes than have been studied.

Why is it so confusing? Because it depends on what you are going to see. In the pitaria laria [phonetic], in the assimilation of the antigens, and the multiplication of the antigens, you have in groups of G1, G2, G3.

The one gene who have more important, having the ORMDLE3. This is the more important genes than we have with the GWAS.

Now, this picture is very interesting because you have a child with exposure to the animals, the stable animals and, also, you have here in the picture milk, which this kid is going to eat, non pasteurized milk. Now, what are you going to think about? Would you have more asthma in this population or in the population that you have your child in a clean environment with antimicrobials and so on? Well, to your surprise, you have less asthma in this population than in the population that you have your child so clean.

You are talking about genetics? There’s a study done in Germany between West Germany and East Germany. The more clean Germany had more asthma and allergy than the German who was more polluted, which is not that we relate it to pollution. Well, they have less asthma with the nice pollution.

This is an interesting study. It’s the Alex [phonetic] Study and what he evaluated the population of children who exposed to - - stables, pasteurized and non pasteurized milk and realized what I was saying, that you are having less asthma in a population which are more exposed to endotoxins.

Talking about polymorphism and CD14, we changed the name. Some, they call it – - 159 and, recently, we call it 260. A doctor in Arizona where the first study was done,

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 15 April 27, 2012 realized that there were variations in the populations related to the amount of IgE. How do you know IgE is increased in allergy patients? They say, Well, we have this SNP and we can’t related it to the variation of the allergy of the patient. But, what happened? It was in favor of these studies in different parts of the world it was done? And, then, came the other group that say, Oh, no, no, no. We don’t find that. So, you have a favor and a non favor.

I think the answer came around when we started to have a study and they analyzed the level of IgE in children raised in different environments. That means that the environment that the child was raised make the variation how the SNP is going to act.

You can see that there was a difference in exposure to stable animals and a special exposure to the cats and the dogs. Well, we know that the dogs seem to be in favor is winning over the cat. But, what happened with the cat? We recommend a cat to a child when he is just a small infant. Well, when we’re talking about the genes and I mentioned the different types of genes, one that is very interesting is the filagreen [phonetic] gene variation of the SNPs. That means that if we test the children and they have problems with the SNPs in the filagreens, then the child’s exposure to cats have a high incidence of noxema [phonetic] and allergy. If they don’t have any variation of the SNPs, you don’t have a problem of exposure to the cat. So, we need to do that before we put the cat in the first year.

After that, they can in different studies, we show different variation of exposure to house - - and there are more studies which start to understand the relationship between the GWAS and the Gee whiz. Genetics, also, is important because this is a variation between females and males. That variation, we start to see also in the white blood cells. Important is the changes in genetics that are produced by cigarette smoking. The cigarette smoking is already changed in the synapse of the patient.

That change is also transferred from one generation, two generations and three generations. We start to evaluate what is the genetics, also, of asthma in Hispanics. We find, then, that they have variations you can see in

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 16 April 27, 2012 relation to the dogs. Still, I favor the dogs. And the cats, they have more reactions to the cat. But that reaction to the cat are different between the White population, the Black and the Hispanics.

But, it’s interesting the variation that you have exposure to the roaches. Because, in the inner city, there are more exposures to the roaches. The White, they don’t react to so much to the roaches. But, the Mexicans and Africans are more sensitive to the roaches. Not only because they are in the inner city, but also genetically. This was a well done study by Dr. Celadon [phonetic] and Joseph El [phonetic].

What is that we see in the variations in allergy in the Mexican population, which are very different than a Spanish population from Puerto Rico? The genetics is not only different in the race, but in the groups. 50 % of the patients, they no [phonetic] reacted to the inhaled corticoids. It’s very common to see that they treat the patients of asthma, they give inhaled corticoids and, then, practically it’s ignored anymore.

Because they have variations in the genetic polymorphism which are going on in different levels. Not only in the phenotypes, in the metabolites and enzymes, in the receptors, in the channels and the carriers.

The P450 [phonetic], you have the lower P450 one to three on the medications. The higher ones are in the hormones. These are some of the samples of medications that you would have in the CP1, 2 and CP13 [phonetic].

As I explained before, the highest we are not going to analyze because they are more related to the hormone, cholesterol, steroid, testosterone and so on. Some of the sample, for example, - - blood level or in - - , cardiovascular medication in - - . This is very important when we’re talking about trials. We don’t have many trials with the minority population. Many of the trials were done before with Caucasian population and you can see tremendous variations that could be between the US population or the Mexican population.

We had a problem when I was over the border when a patient— practically, we lost the patient because the surgeon, they

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 17 April 27, 2012 came from the team from New York, they were not familiar with the different response than they have to the mediasalon [phonetic] in the Mexican population.

You can see that variation is tremendous and they need to be aware of a genetic variation to the drugs. We see in the CIP3 [phonetic] is a slow and has higher levels in Mexicans. Some of the medications to the right. They see 1PD2D [phonetic] have faster in Mexican and slower in the Dominicans and Puerto Ricans. The 2C9 [phonetic] is slower in the Spanish.

Depending on the drugs, you can have so much variations. Important is the drugs on the central nervous system. You see that many of the drugs are the Mexican and the Chinese require much less drugs. There have been legal problems because sometimes, at this dose, are given in the same amount than the Caucasian populations and you can have a problem.

They choose the six [phonetic] genes is also faster in Mexican Americans and slow in Dominicans and Puerto Ricans. It’s interesting this map is immigration and pharmacogenetics. From one side, you have the population that came from Alaska. This was well described by Clara Codesky [phonetic] that showed the - - of alleles between the Eskimos, South Americans and Indians going down to the Aztecs. There was another population, very interesting, we call it from the Big Canoes in which, for example, you find a DNA in the island of Catalina which is from California, but it’s an island. Only you can go by a canoe.

The same DNA was found in Ecuador. So, they were relative and, then, you find it, too, in a population in Chile about 10,000 to 15,000 years ago. This population reached to Tierra del Fuego.

Now, if we start population migrations, we are going to evaluate to the population coming from Africa. They came from this area, but they came from a different part of Africa. They moved through the Caribbean to work in the plantation of tobacco and sugar canes and they mix, for example, the Africans with the Taino Indians in Puerto Rico. The mix of Taino Indians and Africans produce a gene which increase the risk of asthma. We see that in the main

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 18 April 27, 2012 island in the - - Puerto Rico. So, you have a different population.

Very similarly, it was seen in Bair [phonetic] the population in Brazil. They have about the same problem that they have here that we have in Puerto Rico. The other, of course, immigration came from the White population from Europe. But, we don’t have time to go to that.

Here, it is interesting because it’s a nucleotide 3435. You can see this group. This group is coming from Ghana, African Americans from the United States, a little lower in Sudan because Sudan is west of Africa, where you have a mix of Arabs with Africans. Then, you have the White population from Europe much less, and then the population going to immigration going to China and Japan.

We have variation already in the groups that you can see in Chinese and Japanese. This medication, just to give you a little more clear idea, you have in the African American, you see the highest amount. You have the lowest are the Chinese and the Hispanics. In the middle, the Caucasian population. This emphasizes the need for a clinical trial in which we need to individualize all the groups and we can not only say Hispanics. We need to know where they are coming from.

That is the reason that when you study the asthma in Latin America, you can have the different factor variations and frequency in the Hispanics. Thank you very much. Gracias.

FEMALE VOICE 1: Thank you very much, Dr. Quel. Now, questions for Dr. Quel? Please, come up to the microphone please.

FEMALE VOICE 2: Good morning. Excellent presentation, Jorge. Congratulations on that. Why is it that we don’t have that many participation of Latinos in clinical trials? I know that my experience, and I’m Ayuda [phonetic] - - from Chicago—my experience is that Latino physicians are not part of a network where those clinical trials takes place, either because they’re not getting invited and they don’t build partnerships with a - - institution, where the trials are being sponsored or whether they’re not interested or whether they think that their patients would be taken away and put in the trial, so they will lose their patients or

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 19 April 27, 2012 because they don’t have financial incentive if they get invited? Do you have a sense about what are some of the barriers?

DR. QUEL: Yes. For example, in California, some of the centers who have specific populations—San Francisco, for example, have a big group in the study of Caucasians. But, no Hispanics because the investigators, they don’t go to, for example, the central - - or Los Angeles. It’s a - - . They just go to give the money to some of the medical centers who have more specific populations. We see them. There are more Caucasians than really the Spanish in the studies in California.

FEMALE VOICE 2: The question is What can we do? How can we get a Latino physician to be more actively either reaching out, or engaging in whatever or complaining to the NIH? Because, right now, the National Institute of Health demands that there will be minorities and women inclusion in every kind of research. Obviously, if the research comes from pharmaceuticals, then it’s more difficult to have that level of influence.

DR. QUEL: Right. I think we need to move in that direction. Elena Rios is trying to move clinical trials in Hispanics. But, we need to move the Hispanic physicians and the one who takes care of the patients in that direction. We need to ask the pharmaceutical companies that we need to have more minority in the clinical trials, and it’s a must.

FEMALE VOICE 2: Okay, and then the final is more of a comment. I’m part of a national study of Latinos, for the first time, the largest study on epidemiology and cardiovascular. It’s called SOL. I don’t know if any people have heard it and it’s 16,000 Latinos or diverse nationality Puerto Rican, Mexican, Cuban, Ecuadorian, Dominican and all these nationalities. There is a bank of genes, data, that can be analyzed and we are trying to encourage Latinos and others to be interested in looking at the data. Asthma is one of the key areas that we are focusing on, asthma, cardiovascular, including yourselves. I will be available if anyone is interested in knowing how can they have access to that data and how can they start publishing findings. Thank you again.

DR. QUEL: Thank you.

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 20 April 27, 2012 FEMALE VOICE 1: Any other questions for Dr. Quel?

FEMALE VOICE 3: Good morning, Dr. Quel. Thank you so much for your great presentation. I’m a psychiatrist resident from Morehouse School of Medicine of Atlanta, Georgia. I’m a second year and I have - - some information that says that people with asthma has twice the risk of developing mood and anxiety disorders. I would like to hear from you a little bit about your experience with the Hispanic population in relation of asthma with psychiatric disorders.

DR. QUEL: Yes, very good question. I think that depression, anxiety and many of the psychiatric problems we are seeing very frequently the chronic disease. But, also, we see very frequently in asthma. Sometimes, when you try to say, Well, we are treating a patient with some of the medications, psychiatric medications and asthma, it’s nothing wrong with that, because it’s necessarily, and many of the studies are showing improvement in the condition.

But, don’t forget about don’t only treat a patient with psychiatric medications. I remember when I was resident, as I just started my residency, and a patient came with acute asthmatic in the emergency room. The physician says, Well, send it to the psychiatric floor. When they send it to the psychiatric floor, the next day the patient was dead.

That means you need to be treated, yes, for the psychiatric problem. But, you need to treat the asthma.

DR. BEN MEDINA: I’m Ben Medina. I’m from San Diego, a physician in private practice, formerly a machinist [phonetic] for 10 years. My question relates to interstitial lung disease. I know you said some gene phenomenon, in terms of the asthma, is there anything? Is it just that Hispanics do more machinist type work that they get more interstitial lung disease? Or, do you find more interstitial lung disease? Or, is it environmental, or do you know?

DR. QUEL: Well, one of the slides that I presented was cigarette smoke. It has been very high, the incidence of cigarette smoke in the Spanish population and that has been a problem. We have the same problem in China. They have a

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 21 April 27, 2012 very high incidence of cigarette populations. The changes that you can happen in the SNPs from the cigarette smoke, not only is it changed in the mother, but also we see it in the child and the grandchildren. It’s very important and be conscious about cigarette smoke and change in interstitial pulmonary disease.

DR. MEDINA: Thank you.

MS. MARISE SINCLAIR: Good morning. I’m Marise [phonetic] Sinclair from the National Association of Hispanic Nurses, the District of Columbia chapter. Thank you for inviting me to the Association here and inviting the nurses.

My question was, first of all, a comment regarding recruitment of minorities on clinical trials. I think that one thing that we have to keep in mind is that Latino doctors or Hispanic or Spanish speaking physicians are in such a great demand that, in the clinical area, they’re not just heavily utilized, they’re utilized to the point of abuse. I have the tendency to see colleagues work in extended hours and very heavily utilized in any setting, whether it’s in the clinical area or research. So, having said that, I think that one of the goals is to try to step up to the challenge. Even though they are already heavily utilized, perhaps, even allocate some time to really participate actively and incorporate in their current practice clinical trials as if it was part of the standard of care or treatment.

My question was in regards to those two populations that you made the correlation with the genome phenomenon. And, right you are in terms of environmental cues. Those two populations are also heavily exposed to environmental changes like heavily deforestation, organization, water pollution. I wanted to find out if you were able to exactly pinpoint those particulars, besides the smoking factor, if they were other environmental factors that you were able to correlate with that?

DR. QUEL: The comment regarding the money for the Spanish clinical trials. In our center, we have I will say very, very difficult to obtain money from the pharmaceutical companies for Hispanics. It’s not that easy to make a pharmaceutical company give us the opportunity to participate in clinical trials. It’s something that’s

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 22 April 27, 2012 political. It’s something that we need to move in that direction. Because if they don’t support us, it’s very hard to do the clinical trials.

Now, regarding the environmental, one of the concepts in the last few years—I don’t know if you’ve heard about the hygiene hypothesis, which means that we are going to soak clean and clean and clean everything to the microbial. Then, we are not exposing the children to some necessarily endotoxins, to build up the immune response. This is a problem that we have and I say, Maybe we need to give a little dirt to the kids to see if they can do a little more endotoxin. But, it seems to be if it does, then it’s an important factor. Any other questions?

FEMALE VOICE 4: Hi, thank you for your wonderful presentation. I work for AHRQ, the Agency for Healthcare Research and Quality and I am a scientific review officer. It’s about Hispanic participation in the science community, not only in clinical trials. Hispanics are always busy. That, when we are contacting, as a government agency, they say No. You are not at the table. People are going to eat you. I always say, What do you want? You want to be one diner eating the food? Or, you want to be the food? Then, they way that we can start working is participate. When somebody from the NIH, CDC or I’ll call you [phonetic], this is what makes the big differences. Thank you.

DR. QUEL: Yes, thank you very much for the comments. I just, in this moment, came a day ago from the FDA. They tried to eliminate, for example, we know that in inner cities, they are allergic to molds because there are more roaches and molds and dust are more in the inner city. Right now, they tried to eliminate, practically for us, the molds for testing. This is a very serious problem because they want to do two molds than we can do. Now, we do the testing in allergic testing and it costs us about $2. If we need to send to the laboratory, it’s going to cost $20. We are really having different battles in different fields and in which it’s very important that, as Spanish, we need to get involved. Thank you.

FEMALE VOICE 1: Thank you so much, Dr. Quel and Dr. Subar. We talked about two very different diseases and genetic components as to how it relates to our Hispanic Latino

NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 23 April 27, 2012 population. We also talked about that there is very little research being done in our population that our populations are not being represented in this clinical research.

You all got up early this morning to come to this session. Thank you very much. That shows that you are interested in this topic. With that, I would urge you to join the National Hispanic Medical Association because, in numbers, there is power. And, as you saw yesterday when we did our White House briefing, the White House is very eager to hear about what we have to say and what our needs are.

If all of you just went out there and send out the message, we could get many, many people involved in clinical studies and that’s a very powerful thing. That’s my plug for the National Hispanic Medical Association.

I did forget something because I didn’t get my packet until later on. I did not ask our speakers for their disclosures, but they were both just didn’t do anything that was inappropriate. They didn’t tell us anything about their companies. So, thank you very much. I really appreciate that and, anyway, you guys know that whoever signed up for the congressional briefing, the bus will be in the front door at 9:00 and, otherwise, we’ll see you at the lunch meeting, which is at 11:00.

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NHMA – NATIONAL HISPANIC MEDICAL ASSOCIATION NHMA 16th Annual Conference – Innovations that Improve the Health of Hispanics, Families and Communities 24 April 27, 2012