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Good afternoon and welcome to Frankly Speaking About Cancer with the Cancer Support Community. Your host is Kim Thiboldeaux, President and CEO of the Cancer Support Community. This hour is designed to inspire, inform, and to help you live better with cancer. Now here's your host Kim Thiboldeaux.

Kim: Welcome to Frankly Speaking About Cancer, an Internet radio show that focuses on informing and inspiring people to live well with cancer. I'm Kim Thiboldeaux, CEO of the Cancer Support Community. The Wellness Community and Gilda's Club have united to become The Cancer Support Community, one of the largest providers of cancer support in the United States and around the world. Our services are offered at more than a hundred locations worldwide and online at www.CancerSupportCommunity.org.

Well today as part of our special series Spotlight on Metastatic Breast Cancer we’re going to talk about precision medicine, an exciting new approach to cancer treatment. Over the years Frankly Speaking About Cancer has tackled a number of complicated medical topics and precision medicine definitely fits into that category, but we don't shy away from top topics however complex they may seem. Together and with the help of an expert we dive in, we make sense of difficult medical terms and concepts so that you can make the best, most informed decisions for you and your loved ones. That's exactly what we’re going to do today with our guests Dr. James Ford.

Dr. Ford is a medical oncologist and geneticist devoted to studying the genetic basis of breast and G.I. cancer development, treatment, and prevention and families and population. He is currently professor of medicine oncology and genetics at Stanford University Medical Center. Dr. Ford runs the Stanford Cancer Genetics Clinic that sees patients for genetic counseling and testing of hereditary cancer syndromes from prevention and early diagnosis of cancer in high risk individuals and populations. He has recently been named the director of Stanford's New Cancer Genomics Program performing next-generation tumor profiling to identify novel genetic targets for personalized target therapies and he directs the molecular tumor board. Dr. Ford is an editor of numerous scientific journals including cancer research and DNA repair.

He has recently been named the founding editor in chief JCO Precision Oncology. That's quite a bio. Thank you for being with us today Dr. Ford.

Dr. Ford: Well, Kim I am happy to be here. Yes, that was quite an introduction thanks.

Kim: Very impressive so we know we have the right guy on the phone today. Dr. Ford I have to be honest you know I have been struggling with figuring out how to approach talking about precision medicine. I know it's different from other types of cancer treatments so I think maybe we should start by getting our listeners comfortable with some of the medical terms and terminology they are likely going to hear in our conversation. Dr. Ford generally speaking what is precision medicine and why is there so much excitement and hope about it? I mean every time I think of the term my visions have sort of you know Dr. Bones from Star Trek you know treating patients in the Enterprise’s Sick Bay, but tell us what is this modern technology?

Dr. Ford: Yes, well I think that's the ultimate goal though you know we’re only part of the way there so I agree it's important to think about some of the definitions and what we’re really talking about. I think this idea of precision medicine in an overall way just really means using some of the incredible advances and tools to measure things and in terms of medicine and clinical things you know we’ll talk about today about measuring DNA and sequencing DNA, but it can be as broad as you know a watch that's counting your steps. Anything that is helping to measure and quantify things at a very personal level I think is what we’re calling precision medicine to be more precise about the measurement as we'll talk about and the whole idea is to take that to better tailor schemes and that could be for treating diseases like we’ll talk about today, but also for maintaining health, but to do those interventions or schemas in a way that’s precise and tailored to an individual as opposed to a general population.

Kim: Let's dive in a little on the topic today. We’re talking today about precision medicine as it relates to metastatic breast cancer. Can you tell our listeners what metastatic means and how metastatic breast cancer is different from or the same as breast cancer?

Dr. Ford: Sure, well the term metastatic in cancer medicine and oncology simply means a tumor that has spread distantly from the primary site. That patient could present that way or that might be there the result of a recurrence of a primary cancer that was already treated. Specifically in the breast cancer setting, metastatic breast cancer means cancer adenocarcinoma that has spread beyond the breast and up and above the lymph nodes, but more commonly we think of metastatic as if it spread for example to the liver or to the bones or to the brain. Again as I said that could be the first presentation of breast cancer, but fortunately today that's less common with good screening, but it still unfortunately can happen as a recurrence of a in a woman who has been treated for her primary breast cancer, but at some point later develops a metastasis.

Kim: I know that you know we’re going to talk a lot about different precision medicine options that are available for someone diagnosed with metastatic breast cancer, but just give us an overview of some of the other kinds of therapies that we hear about. I know it’s a lot to cover in a short time, but I know we hear about you know chemotherapy, hormone therapy, immunotherapy. Can you just talk about these in just as simple as possible terms to again sort of lay the groundwork for our discussion.

Dr. Ford: Sure, of course there's a whole spectrum of treatments, but it's particularly relevant for breast cancer because the whole spectrum really is is used in different situations and in different points in time. You know so most generically the terms chemotherapy is simply means a drug, a small molecule that’s cytotoxic hopefully more so to cancer cells than to normal cells, but that definition belies the fact that they're often not very selective or specific. They're just generally toxic and for a whole variety of reasons they may be more toxic to particular cancer cells or cancer types, but they generally often have broad side effects because they're not perfectly specific. Some of the newer approaches of course hormone therapy is very relevant for breast cancer because it's a hormonally driven.

Often hormonally induced cancer and so various approaches to interrupt that hormone’s action so anti-hormone drugs like tamoxicinin are important for many women with breast cancer. We’re hearing you know enormous amounts about immunotherapy, which is not a new approach to cancer, but the efficacy has definitely improved with some of the new agents that have been discovered recently. The idea here is you know in theory you’d think our immune system would identify cancer as not normal as you know not ourselves, just like it identifies a bacterial infection, but for many many reasons cancer is very smart and has figured out how to avoid that natural immune reaction. Lots of research has resulted in the current state where we can manipulate the immune system to try to get around that avoidance and some of the new immunotherapy drugs do just that.

They help they help inspire the natural immune system to reject cancer and have been effective in certain situations and then finally this idea of quote targeted therapy. I mean that term is very broad, but just I think in general we mean a drug or an antibody or a therapy that specifically targets a particular gene or gene products or mechanism in a cancer cell so more specific than just being generally cytotoxic. We’ll come back and talk about for example targeted therapies to HER2 and those will be you know binding that very HER2 molecule so very targeted and we hope that the side effects of those will be less because they're more specific to the abnormality in the cancer cell.

Kim: As we continue down this road of trying to understand some of these terms and terminology that we’re going to continue to use throughout the show, Dr. Ford what about a biomarker. What is a biomarker? How does that relate to precision medicine?

Dr. Ford: Well, I think that's just a generic term for any molecule in the human body that we can measure that helps us to either predict whether a certain treatment might work for that disease and in this case cancer or it might be prognostic for how this how likely it is that a cancer for example may recur or not recur or to even follow a therapy to be able to measure how well that therapy is working. For example, often we hope that these biomarkers will be simple to measure you know so if this is a circulating marker in the blood that relates to a cancer progression or a response obviously is an easier task than doing a CAT scan and measuring it. Often they correlate so I think any measurable and again here's when we come back to be as precise as possible so it's something that can be measured and can help tell us about how a cancer is progressing or responding or what type of cancer it is even would be termed a biomarker.

Kim: Dr. Ford sometimes I hear the terms precision medicine and personalized medicine used interchangeably, but that's not really correct is that right?

Dr. Ford: Well you know these terms are also overlapping and it kind of depends on the definition of the person using them. I guess conceptually I think of precision having to do with the measurement, the technology of measuring it to be more precise in measuring you know whatever this abnormality is and the personalized part is using that precise information to try to tailor a therapy to an individual so that means you know that we would treat a patient with breast cancer in a particularly specific way depending on her precise measurements of her tumor as opposed to just you know every woman with breast cancer and you know what generally works or doesn't work you know across that whole spectrum.

Kim: We've got a couple of minutes ‘til our first break here, Dr. Ford, but the data I've seen shows that people are living longer with metastatic breast cancer than they have been in the past say than they were 10 years ago. Has precision medicine contributed to that improved outcome?

Dr. Ford: Yes absolutely and as a great example you know I think I mean we sometimes get so wrapped up in this whole precision medicine as this whole new field that came out of no place, but in fact precision medicine has been going on in breast cancer for decades. Excellent examples are targeting the estrogen receptor with tamoxifen, an anti-estrogen drug or targeting the HER2 gene with Herceptin, an antibody. Those are precision medicine targeted therapy approaches and they’ve clearly led to improved survival in breast cancer. More recently you've heard about PARP inhibitors being approved for certain subgroups of breast cancer that have bracket mutations, clearly improving survival in patients with metastatic breast cancer.

Kim: Great, great. This is Frankly Speaking About Cancer. We’re talking today about metastatic breast cancer with Dr. James Ford from Stanford. We’re going to take a quick break here and we will be right back.

Become our friend on Facebook. Post your thoughts about our shows and network on our timeline. Visit Facebook.com/VoiceAmerica.

Effective cancer treatment requires more than just medication or surgery. With the country's 12 million cancer survivors and their loved ones, the social and emotional challenges of adapting to life with cancer are ongoing. How to handle coworkers questions, how to get comfortable with new physical realities, how to reassure worried family members or explain to friends your priorities have changed. The Cancer Support Community is ready to help by providing free counseling, education, and hope for survivors and their caregivers whether online or at over 100 locations around the world. The Cancer Support Community is ready to offer the support you need to live a better life with cancer. For more information on support groups, publications, nutrition, exercise programs, and more call 1-888-793-9355 or visit us online at www.cancersupportcommunity.org. That’s cancersupportcommunity.org. The Cancer Support Community, a global network of education and hope.

Cancer Support Community is proud to be a partner of Magnolia Meals at Home, a new pilot program that aims to help patients by providing nourishing meals to households affected by breast cancer so loved ones can spend more quality time together. This program is currently available in and around two pilot cities and over Massachusetts and Woodcliff Lake, New Jersey. Participants will receive one delivery of meals every month for up to six months when enrolled in the program. Each delivery includes up to seven meals designed to help meet that their nutritional needs of people living with breast cancer and 10 meals for family members. This novel program is brought to you by the Eisai Women's Oncology Program, Magnolia, Cancer Care, The Cancer Support Community, and Meals on Wheels Association of America. To find out if you or loved ones are eligible visit online at www.Magnoliamealsathome.com or call 617-733-5848.

Hi I’m Nick Nicolaides, President and CEO of Morphitec and we’re delighted to be a sponsor of Cancer Support Community’s Frankly Speaking About Cancer series. Morphitec and his parent company Eisai are committed to human healthcare and we recognize that patients and the families are the most important participants in the healthcare process. We salute our global advocacy partners who are devoted to improving the lives of people touched by cancer every day.

Cancer, it's a lonely word. Terms I don't understand, choices I never thought I’d have to make, but there is hope and help. Support from cancer survivors, links to research, and clinical trials. Help with finances and access to care all behind you with Break Away from Cancer. Created by Amgen to empower cancer patients. The Cancer Support Community is proud to be a partner of break away from cancer.

Have you friended us on Facebook yet? Why not? Just go to Facebook.com/VoiceAmerica or search for the keywords Voice America. Once you are a part of our Facebook network you'll receive daily messages about what's happening with our shows, this week's featured guests, and new happenings at the Voice America Talk Radio Network and you can add your voice to the always active discussions on our timeline. Just go to Facebook.com/VoiceAmerica or search for Voice America.

You are listening to Frankly Speaking About Cancer with the Cancer Support Community, an inspirational program offering the resources you need to live a better life with cancer. Now here's your host, Kim Thiboldeaux, President and CEO of the Cancer Support Community.

Kim: Welcome back to Frankly Speaking About Cancer. I'm your host Kim Thiboldeaux. Our show today is about precision medicine and how it's being used to treat people facing metastatic breast cancer. Our guest is Dr. James Ford. Dr. Ford is currently professor of medicine, oncology, and genetics and director of the Stanford Cancer Genetics Clinic and the cancer genomics program at Stanford University Medical Center. You know as we discussed before the break metastatic breast cancer is an advanced form of breast cancer in which the cancer has metastasized or spread to other parts of the body.

We also talked about biomarkers and how they can help provide doctors with more information about a person's cancer. I just I want to dive in a little bit deeper on that now, Dr. Ford and maybe dive in on or again some terms folks may have heard of or want to learn a little bit more about. I know we certainly hear about the term HER2 or HER2 Positive. Can you talk us a little bit about what HER2 means?

Dr. Ford: Sure, yes I mentioned that right before the break so HER2 is just the name of a protein that's normally expressed in breast and other cells and is encoded by a gene called ERBB2. You’ll hear that as well. We use those terms interchangeably for the complex nomenclature of all of the stuff in genetics, but that protein what is normal function is to do is a growth factor. It helps translate signals that are coming from outsider cell to cull that cell it should grow faster and divide right and that of course is one of the abnormal aspects of cancer so HER2 can get amplified so it is inappropriately expressed at high level and that means that growth signal is getting inappropriately translated and is driving the cell division.

That's how it's potentially causing cancer and certainly contributing to breast cancer. It’s inappropriately amplified or overexpressed in about 20% of breast cancer. Really one of the major discoveries in breast cancer over the last several decades was that targeting that HER2 protein and initially that was done with an antibody that people know of as Herceptin or Trastuzumab is his other name was very effective in treating that 20% of women whose breast cancer is overexpressed HER2. I think as a really classic example of precision in targeted medicine in how understanding that molecular underpinning of a subgroup of breast cancer helps Taylor that treatment because Receptin doesn't work in the other 80% of breast cancer that is not over expressing HER2.

Kim: Do we know in terms of patient being you know HER2 positive doesn't mean anything in terms of their prognosis or what we know about their cancer or does it just mean that we found a target that we can more precisely treat?

Dr. Ford: Well in fact both and that's a fascinating aspect of this. Before the era of having a drug against HER2 or an antibody we did know that HER2 is a bad prognostic sign. It meant that HER2 overexpressing or amplified breast cancer has actually had a poor outcome. They were more aggressive and more likely to recur and metastasize, but of course that has all changed in the area of having an effective treatment for HER2 cancer and so those numbers have improved dramatically so it had both prognostic implications and predictive, meaning predictive that those HER2 positive breast cancers would respond to HER2 directed therapies.

Kim: Let me get into another area that's been in the news it seems lately. We’re hearing a lot about triple negative breast cancer. What is triple negative breast cancer?

Dr. Ford: Yes so a very interesting topic because triple negative breast cancer basically is a diagnosis of exclusion. We talked about HER2 Positive and as you know many breast cancers also overexpress the estrogen receptor so they are called ER Positive for which we have targeted therapies with anti-estrogen molecules and other hormones. Triple negative simply means that that breast cancer cell does not overexpress HER2 nor ER nor another hormone receptor called progesterone receptor PR. ER Negative, PR Negative, HER2 Negative, ER Negative, PR Negative is what's called Triple Negative breast cancer. Well we know that that’s probably lots of different types of breast cancers all bundled together, but is an example of breast cancer for which we don't have a targeted therapy.

We can’t use Receptin. We can’t use Tamoxifen so until at least recently most of them got more general cytotoxic drugs like Adriamycin and Paxol and others that could be effective, but they are aggressive cancers and constitute you know again about another 20% or so of all breast cancer.

Kim: Because of the challenges in treating it is it more aggressive? Is it more deadly?

Dr. Ford: Yes, it often is more aggressive and deadly and not every case, but that's why I think there's a particular need for developing better therapies for this triple negative group.

Kim: Yes, yes let's move on Dr. Ford to BRCA again I think were hearing more in the media about BRCA genes which can be inherited so a few questions what do we know about metastatic breast cancer and inheritance and what are the you know BRCA genes and why is it useful to determine if a patient has them?

Dr. Ford: Absolutely so a big area and related to the idea of triple negative breast cancer because often these two things—done that always are related to each other. As you know BRCA genes, BRCA1 and two are the cause of much of hereditary breast and ovarian cancer. They are not the only genes, but they were certainly the first ones discovered in our constitute the largest group of genes that confer that so we think lots know about testing for BRCA1 or BRCA2 mutations in the germline of individuals with a significant family history of breast and ovarian cancer and that means the DNA that you inherit from your parents so not DNA from the tumor, but DNA from your normal cells to predict if you're at high risk for getting breast cancer and to implement tools to try to screen and prevent that situation. It also relates to the tumor themselves and what you're talking about in terms of metastatic breast cancer so many of the cancers that develop particularly in BRCA1 meet in carriers, but also BRCA2 are these triple negative breast cancers.

That doesn't mean that every triple negative breast cancer that's caused by BRCA1 or 2 mutation, but they are related and some of the therapies that we’ll talk about in a minute that are targeted to BRCA1 or 2 we think are also relevant for triple negative breast cancer. Now the idea of do these hereditary factors relate to a high risk of metastasis is not so clear. They clearly increase the risk of breast cancer to begin with and often aggressive breast cancer like triple negative breast cancer but we don't think they necessarily are a cause of metastasis. In fact we don't understand the genetics of what causes metastasis too well.

There are a number of other genes that are studied in research settings that we think may be involved. Of course those will be great targets for therapies to try to prevent metastasis, but in terms of BRCA1 and BRCA2, the risk of metastasis still is largely driven by how advanced the cancer was when it presented and if it has spread to lymph nodes and some of those classic measurements.

Kim: Dr. Ford are there other genes that have been connected to metastatic breast cancer? Are we continuing to study that?

Dr. Ford: Well, I think so many people are studying genes and the mechanisms of what causes cancer cell to move from a primary site in the breast to metastasizing to other organs, but I think we’re still in the early days of understanding that, but is a major targeted research because that would be a great focus for therapies or drugs to try to interrupt that metastatic process after a primary cancer is discovered.

Kim: Dr. Ford we've had some patients ask us how and where is biomarker testing performed and how long does it take for the results to come back?

Dr. Ford: Sure, well that's a really broad question because this term biomarker encompasses all sorts of different tests right, but a few examples right when a woman presents with a new localized breast cancer so a breast cancer in her breast and has a biopsy or surgical excision of that. Standard of care is to measure a number of biomarkers that we've already talked about ER, PR, HER2, and other things. Those are all biomarkers to help understand the nature of that breast cancer.

At the other end of the spectrum, a woman with a metastatic breast cancer may have a what we’re calling genomic profile or tumor genomic test and that's looking off in that hundreds and hundreds of genes and biomarkers to try to identify specific alterations in that woman's tumor. Those can take you know many weeks sometimes to get the result or as what we’re talking about formally often is done within a day or two. It's hard to generically answer that, but of course the goal for all of this is to turn these tests around in a rapid enough fashion that is relevant to taking care of patients, not just a research tool.

Kim: Yes, we’re coming up about a minute and half to our next break here Dr. Ford, but so we can help women who are listening so they’re diagnosed with breast cancer, what should they be asking for are they you know patients don't want to seem pushy, but they want to be educated and make sure they're getting all the right tests.

Dr. Ford: Exactly and you know so you want to make sure your oncologist and your surgeon and radio therapist and all of the doctors you are talking to are familiar with all of this, which certainly they are in any excellent breast center and oncology group. You know much of this for breast cancer is very standard now in terms of ERP or HER2 testing. Some of these more experimental or investigational things are more centered in cancer centers or places involved in clinical trials and of course they're asking for referrals or second opinions to get some of those tests is always appropriate.

Kim: Really patients should be educated, should be empowered. What you’re trying to do some of that today.

Dr. Ford: Absolutely.

Kim: We have an open and honest conversation with their doctor and be asking these questions about these important tests that really can in many ways help to inform the you know, the treatment plan and the treatment protocol so the patient can have the best possible outcome. This is Frankly Speaking About Cancer. We have a spotlight today on metastatic breast cancer, specifically around precision medicine. We’re here with Dr. Ford from Stanford. We are going to take a quick break here on Frankly Speaking About Cancer and we will be right back.

Become our friend on Facebook. Post your thoughts about our shows and network on our timeline. Visit Facebook.com/VoiceAmerica.

Effective cancer treatment requires more than just medication or surgery. With the country's 12 million cancer survivors and their loved ones, the social and emotional challenges of adapting to life with cancer are ongoing. How to handle coworkers questions, how to get comfortable with new physical realities, how to reassure worried family members or explain to friends your priorities have changed. The Cancer Support Community is ready to help by providing free counseling, education, and hope for survivors and their caregivers whether online or at over 100 locations around the world. The Cancer Support Community is ready to offer the support you need to live a better life with cancer. For more information on support groups, publications, nutrition, exercise programs, and more call 1-888-793-9355 or visit us online at www.cancersupportcommunity.org. That’s cancersupportcommunity.org. The Cancer Support Community, a global network of education and hope.

Cancer Support Community is proud to be a partner of Magnolia Meals at Home, a new pilot program that aims to help patients by providing nourishing meals to households affected by breast cancer so loved ones can spend more quality time together. This program is currently available in and around two pilot cities and over Massachusetts and Woodcliff Lake, New Jersey. Participants will receive one delivery of meals every month for up to six months when enrolled in the program. Each delivery includes up to seven meals designed to help meet that their nutritional needs of people living with breast cancer and 10 meals for family members. This novel program is brought to you by the Eisai Women's Oncology Program, Magnolia, Cancer Care, The Cancer Support Community, and Meals on Wheels Association of America. To find out if you or loved ones are eligible visit online at www.Magnoliamealsathome.com or call 617-733-5848.

Hi I’m Nick Nicolaides, President and CEO of Morphitec and we’re delighted to be a sponsor of Cancer Support Community’s Frankly Speaking About Cancer series. Morphitec and his parent company Eisai are committed to human healthcare and we recognize that patients and the families are the most important participants in the healthcare process. We salute our global advocacy partners who are devoted to improving the lives of people touched by cancer every day.

Cancer, it's a lonely word. Terms I don't understand, choices I never thought I’d have to make, but there is hope and help. Support from cancer survivors, links to research, and clinical trials. Help with finances and access to care all behind you with Break Away from Cancer. Created by Amgen to empower cancer patients. The Cancer Support Community is proud to be a partner of break away from cancer.

Have you friended us on Facebook yet? Why not? Just go to Facebook.com/VoiceAmerica or search for the keywords Voice America. Once you are a part of our Facebook network you'll receive daily messages about what's happening with our shows, this week's featured guests, and new happenings at the Voice America Talk Radio Network and you can add your voice to the always active discussions on our timeline. Just go to Facebook.com/VoiceAmerica or search for Voice America.

You are listening to Frankly Speaking About Cancer with the Cancer Support Community, an inspirational program offering the resources you need to live a better life with cancer. Now here's your host, Kim Thiboldeaux, President and CEO of the Cancer Support Community.

Kim: Welcome back typically speaking about breast cancer. I’m Kim Thiboldeaux in today's episode is part of our special series, Spotlight on Metastatic Breast Cancer. We are lucky to have with us Dr. James Ford to help us better understand precision medicine and its application to treating metastatic breast cancer. Dr. Ford is a medical oncologist and geneticist at Stanford devoted to studying the genetic basis of breast and GI cancer development treatment and prevention in families and populations. Dr. Ford earlier in the show we talked in general terms about different forms of treating cancer and now I would like to take a deeper dive with you and see how precision medicine is applied to metastatic breast cancer. There are a lot of new precision medications that have become approved for the treatment of metastatic breast cancer with specific biomarkers you know in the category of targeted therapy so let's walk through each biomarker and see what scientists you know have created and how we sort of advanced treatment based on you know this new science and our new knowledge. Let's start by looking at what targeted therapies are available in response to HER2 positive diagnosis. How do they work to treat metastatic breast cancer and how are they administered?

Dr. Ford: Sure, as we talk about it a few minutes ago you know maybe 20% or so of breast cancers will overexpress or have amplified this HER2 gene and it can be targeted in a number of ways. The initial and classic example is Trastuzumab, which is an antibody. It’s also called Herceptin and of course that is FDA approved for treatment of HER2 positive breast cancer, but there's a whole list of additional antibodies and now other drugs that are involved in that. One is called Pertuzumab and there’s drugs that are not antibodies, Lapatnib and Neratinib and others that all target HER2 and all have different levels of activity and of course now people are starting to combine them together so Trastuzumab plus Pertuzumab seems to work better than one alone so the usual ways that oncology gets tested out.

A really interesting new one is called TDM1 and that's an example of a class of therapy called antibody drug conjugates so they’ve basically taken the antibody against HER2 and they’ve hooked it up to a toxic molecule, one that’s so toxic you can't just give it systemically to a person, but now you're targeting that toxic drug right to those HER2 positive cells and they selectively get taken up by that cell and it has been shown to be effective in HER2 positive cancers. Even some that aren't treated very well with the existing antibodies so a really interesting field and improving all the time.

Kim: How about Dr. Ford for patients whose biomarkers show that hormones are playing a role in the development of their cancer. Talk to us about that and talk to us a little bit about you know the difference between a woman whose premenopausal versus postmenopausal and how that sort of impacts treatment.

Dr. Ford: Sure well of course the hormone responsiveness of breast cancer has been a target for therapy for 40 years now so those breast cancers that are estrogen receptor positive and of course that’s the majority of breast cancer in women who are postmenopausal are responsive often quite so to a whole variety of hormonal manipulations. They are like me way more than we could even talk about here, but Tamoxicin is the classic anti-estrogen drug that has been used, but there’s many others now. Of course we’re familiar with what we call AIs or Aromatase Inhibitors and Astro Sol, Letra Sol and others that also interrupt that estrogen responsive cascade and others. Drugs that are targeting things like what are called the mTOR Pathway have Relimous and others are active in this hormonal responsive cancers.

Some of these drugs and can be used in any ER positive breast cancer, but some we don't use in premenopausal women because their ovaries are still producing estrogen and that counteracts the effects of these drugs. That's why your doctor will sometimes recommend different drugs if you're postmenopausal versus premenopausal or if you had your ovaries taken out for some reason.

Kim: What about patients with the BRCA1 or BRCA2 gene what targeted therapies are available for them?

Dr. Ford: Well this is a really interesting area, which there’s been a lot of developments recently and in fact new drugs approved just this year so and this is a great example of really using translational and preclinical science to inform identifying therapies and targets. It turns out the BRCA1 and BRCA2 are DNA repair genes so they are involved in fixing DNA strand breaks that can occur in our normal cells for a whole variety of reasons. When they’re defective like BRCA1 or BRCA2 mutant cancer cells, those cells don't repair as well and they accumulate lots of other mutations. That's probably why they’re a cancer risk gene, but that also that sort of an Achilles' heel as a target and so DNA repair inhibiting drugs have been developed that turn out to be very very active in BRCA1 or BRCA2 mutant cells.

This is a great example again of targeted therapy to the underlying genetic defect in those cells and a PARP inhibitor called Olaparib was just approved this year based on its improved survival in women with metastatic BRCA1 or BRCA2 mutant breast cancer who are on that oral agent. It's a pill. Has relatively few side effects, far easier to take than cytotoxic drugs and there is a series of other PARP inhibitors that are being tested right now that will no doubt get used in breast cancer and maybe effective in the larger group of triple negative breast cancers potentially combined with other drugs in many many trials looking at that area right now.

Kim: Dr. Ford if somebody has a history of breast cancer in their family should they talk to their doctor about whether they should be tested for the BRCA gene?

Dr. Ford: Absolutely and so this is a really important area that genetic testing has become so much easier, less expensive, and more rapid that it's much more accessible than it was just a few years ago. There's all sorts of guidelines on who should be tested, but in general a family history of breast or ovarian cancer or any woman who has breast cancer at a particularly young age. Anyone under 45 or triple negative breast cancer under 60 and other situations should certainly be considered for BRCA1 or BRCA2 testing. We worry that not enough women are being tested for this and that now there's a therapy that's related to that mutation in addition to that mutation just giving family information that that will drive more women and doctors to order that and identify this patient that's a potential good candidate for PARP inhibitor and other drugs coming in down the line.

Kim: Dr. Ford in my research I notice that there may be more than one targeted therapy for a biomarker. I mean that's probably the good news right, we’re bringing more and more therapies to market. The research has really accelerated. I know there are a lot of drugs in cancer pipelines today, but how does the doctor decide which one to use? I mean I'm assuming it's a little more complicated than choosing between you know Advil and Motrin so what are the factors that go into that decision?

Dr. Ford: It turns out to be incredibly complicated and it's one of the areas we’re trying to get our head around better is how to choose between targeted therapies or combine them if you have multiple choices. Sort of two sides to the coin here. Even beyond what we were talking about so far in some of these large scale genomic test we do on tumors sometimes you can identify five, ten, or more potential targets in a complicated metastatic tumor. How do you pick which one is the most important one or where do you start and can you combine.

These are all questions that we don't really have magic answers to and are kind of learning our way. First off combining different targeted drugs isn't always so easy. Sometimes you get side effects when you combine two different drugs that weren’t expected or you didn't know about. Traditionally, phase I trials would be done at any new phase one or two trials on any new combination to look for side effects and to escalate doses and all of these, but as we get in to all of these new targeted drugs and the incredibly complex genetic profile that tumors has, it quickly becomes exponential to try to think about doing a trial for every conceivable combination of all of these different things. It is difficult and other approach is to sequentially use one and then another and go on that and that might be safer, but it might be a little bit slower and we’re still learning about if you have a choice, which one should you start with? We like to use the word driver. You know can you identify the driving mutation the one that seems central to that tumor. A lot of research is going into ways to try to better pick that out. I think that's an evolving topic that we need to get smarter at over the next few years.

Kim: Interesting interesting. Dr. Ford we've got a couple minutes until our next break here, but let's just talk for a minute about about side effects. You touched on that in your last comments, but what do we know about sort of the typical side effects that patients experience when they take a targeted therapy and are they different than let's say someone who is on a more traditional chemotherapy and then just a follow on. I know that we’re doing a lot of combination treatment, may be a you know targeted therapy with a more traditional chemo and does that affect the side effect profile?

Dr. Ford: Yes, well of course you know everybody hates the side effects of quote traditional chemotherapy and cytotoxic drugs and they are significant and of course that's one of the driving motivations to try to get to more targeted, more selective therapies because we hope they have less nonspecific side effects and more specific toxicity or anticancer activity. In general, that's true so many of these newer targeted therapies are far less toxic to take and have fewer side effects so I always caution people that's not completely true just because it’s a targeted therapy, it doesn't mean it has no side effects and some of them can have significant side effects or be very variable not have side effects at all in one person and be severe in another. Again you know it's all learning about new drugs and what the chances are. The immunotherapies are a good example of this. Of course they can be incredibly effective and often are have no side effects at all are very easy to use, but you can develop all sorts of typical side effects. You're essentially inducing autoimmunity and people can get inflammation of different organs and very severe effects so it's too facile to equate targeted with non-toxic so that clearly is the goal.

Kim: Right.

Dr. Ford: I think we’re moving in the right direction.

Kim: Great terrific good to know and to understand you know as the science evolves. This is Frankly Speaking About Cancer. We’re talking today about metastatic breast cancer, precision medicine, targeted therapies. We’re talking with Dr. Ford from Stanford University. We have a lot more to discuss with Dr. Ford. We’re going to take a quick break don't go away will be right back.

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You are listening to Frankly Speaking About Cancer with the Cancer Support Community, an inspirational program offering the resources you need to live a better life with cancer. Now here's your host, Kim Thiboldeaux, President and CEO of the Cancer Support Community.

Kim: You're listening to Frankly Speaking About Cancer. Today's episode is part of our special series Spotlight on Metastatic Breast Cancer. I'm your host, Kim Thiboldeaux and we've been having an in-depth and insightful conversation with Dr. James Ford about precision medicine and metastatic breast cancer. Dr. Ford let's take a minute, tell us a little bit more about you. How did you become involved in cancer treatment and genomic research?

Dr. Ford: Well I've really been doing it since I was in medical school. When I was a student at Yale, I worked in a laboratory that worked on drug resistance. Obviously a major focus of cancer treatments and challenge and have ever since. Those studies involve pharmacology and molecular biology. Here at Stanford, I trained in oncology obviously and in genetics and so I was very fortunate to come onto the faculty and start my research career right as some of these cancer genes are getting discovered like BRCA1, BRCA2, and others. Early on I focused on how those cancer genes affect cancer risk and could they be targets for therapy so remarkably exciting that over the course of my career of 30 years that we've actually realized some of those goals and identified drugs that work in those pathways.

Kim: Did you know from a young age that you wanted to be a doctor or did you want to be sort of a you know a fireman or a famous tennis player or what?

Dr. Ford: Well when I was an undergraduate I thought I was going to be a jazz bass player, but those hopes were faded so I think I landed better in medicine. I was also interested in science and in medicine and so I think I definitely found my place.

Kim: Are you still interested in music?

Dr. Ford: Yes, yes. From the audience point of view no.

Kim: Outstanding. Tell us a little bit more about the work at Stanford, at the genetics clinic in the cancer genomics program there.

Dr. Ford: Well when I joined the faculty over 20 years ago now we started at a cancer genetics clinic here so a hereditary cancer genetics clinic. This is you know widespread across the country now, but those were early days, just a few years after discovering some of the important cancer susceptibility genes for breast and ovarian cancer and colon cancer and others. That was taking advantage of genetic counselors who are critical to this process and seeing patients for counseling and genetic testing. That's grown from a cottage industry to a incredibly busy clinic in terms of genetic testing here and everywhere over the last two decades.

That kind of led naturally to in my own research in DNA repair and cancer genetics to thinking about this idea of profiling tumors and trying to target those, but often around the same genes, but more with the idea of trying to identify therapies as opposed to just identifying individuals at high-risk to try to prevent cancer and so here in many places I think that's one of the most exciting things going on in cancer is trying to find the right place for this approach among the spectrum of cancer treatments.

Kim: Now that you're so entrenched in the research and I'm sure have your finger on the pulse of the national and even international you know conversation on this, can you tell us is there any metastatic breast cancer research, diagnosis, treatment that we should put on our radar, exciting trials. You know what's next in the advancement of this treatment and care.

Dr. Ford: Well, so many things and I'll just pull a few out. One thing we haven't talked about at all in terms of a subgroup of breast cancer is that has been highlighted by all of these recent genomic studies are alterations in some other genes. Genes such as the PI 3-kinase, AKT, other genes for which targeted therapies are just emerging and we’re hearing a little bit about clinical trials targeted to them. I think there's going to be many many more targets in subdivisions of breast cancer that we’ll think about more specifically. Another area I think is incredibly exciting for all of genomic oncology, but relevant to metastatic breast cancer is that we can measure DNA in our plasma, in our circulating blood and we can pick out the needle in the haystack of DNA molecules that contain those mutations that occurred in the tumor and differentiate them from all of the normal DNA that's floating around.

That has amazing potential to try to with a simple blood draw measure genetic changes in tumors just like we’re doing in the tumors themselves now and follow as the ultimate biomarker the genetic change in that tumor in the blood. Is it responding to a targeted treatment? Is it showing evidence of resistance so I think this whole idea of what's called liquid biopsies and circulating DNA is going to be very exciting over the next few years.

Kim: Wow. You know Dr. Ford so much sort of the testing and the treatments that we’ve discussed today are very exciting and obviously you’re in an outstanding institution, like Stanford one of the big academic centers, but we do know that the majority of patients are being treated in the community setting in the United States. They're not treated at the big cancer centers so what do we know about these tests and these treatments in terms of their availability to patients, in terms of their community doctors being on the cutting edge, and in terms of sort of access and affordability to these tests and treatments.

Dr. Ford: Yes, well these are all important and big questions that face you know healthcare in the United States overall and of course relevant here. I think I would say that much of what we talk about today really is available across the country and not only in a specialized setting. Particularly for taking care of newly diagnosed primary breast cancer. All of the discussion about HER2 and ER and profiling those tumors and tailoring the treatment I think is. I think we treat breast cancer you know very well in this country and that is going on everywhere. When we get to women who unfortunately have metastatic breast cancer particularly if they’ve progressed on some of the standard approved therapies you know that's the situation then where I think one wants to think about potentially getting a second opinion or going to a center or at least talk with your doctor about potential trials that might be more relevant for you at that point because often those are only available at those places.

All that being said I think there's definitely a democratization of this because of the ability to do tumor profiling for so much less money and so much faster than just a few years ago when that really only could happen at a major research center. Now there's commercial labs and other places that can do those tests so the availability is there. I think it's just important to talk to your doctor about those opportunities and even encourage them to explore those or talk to their colleagues about them if they're not as familiar.

Kim: Dr. Ford we’re quickly coming unfortunately to the end of our show. It has been a very informative discussion, but before we sign off just a you know quick word of advice to our listeners if they’re diagnosed with breast cancer or metastatic breast cancer just any quick advice that you would give them?

Dr. Ford: Well just that there’s so many opportunities and there’s so much research going on you know. You know, it's not a magic bullet coming out, but the whole idea of understanding your cancer more closely with these precise tasks are only going to help identify a better and more tailored therapy for you and that work is continued so I am very excited about the future, but I think we’re also proud about the great progress that has been made in the last half century in a breast cancer.

Kim: Fantastic, Dr. Ford. I want to thank you so much for coming onto the show today and helping us better understand precision medicine, breast cancer, metastatic breast cancer, the information and insights and wisdom that you shared with us are without a doubt invaluable to our listeners. I want to remind folks who are listening today that we have a whole range of education and support services at the cancer support community. We have educational materials. We have support groups, educational programs, nutrition, exercise, stress reduction.

All of these programs and support services are free of charge for women with breast cancer or anybody with any kind of cancer and for their family members and loved ones. We have 47 centers around the country where we are providing all of these free services. You can find a list of our centers at www.cancersupportcommunity.org. You can also call our helpline at 888-793-9355. You could call right now.

Talk to one of our counselors at 888-793-9355 and certainly all of us at the cancer support are proud to create and bring you this important series on metastatic breast cancer. We’re grateful to Lilly oncology for providing the educational grant allowing us to do this programming and education. Again, if you want to find out more about our free support and education and navigation services. Visit us at cancersupportcommunity.org or you can call us at 888-793-9355. My name is Kim Thiboldeaux from the Cancer Support Community. This is Frankly Speaking About Cancer. Until next time be well, do well, live well.

Thank you for joining us for Frankly Speaking About Cancer with your host, Kim Thiboldeaux. We’re here for you every Tuesday afternoon at 1 PM Pacific time and 4 PM Eastern time on the Voice America Health and Wellness Network. In the meantime stay connected online at cancersupportcommunity.org. That’s CancerSupportCommunity.or