Ovarian Cancer Talk Transcript

Moderator – Tim Wenger: Direct from Roswell Park in Buffalo, New York, this is a conversation about ovarian cancer. My name is Tim Wenger. And throughout this conversation, we'll hear from four multidisciplinary experts here at Roswell Park. The conversation will be about treatments, diagnosis, new therapies. We'll talk about immunotherapy. We'll talk about genetics. We'll talk about hope with regard to ovarian cancer.

Throughout this broadcast, we'll also be able to accept questions from you, live. We've received several questions via social media platforms along the way, but if you haven't thought of one yet and you are going to, it's really easy to do. On your screen, you can use a chat feature by going to roswellpark.org/ovariancancertalk. That's how you got here to begin with. You can also tweet your question out during the conversation using the hashtag #ovariancancertalk. And also post your question or comment on Roswell's Facebook page which is simply facebook.com/roswellpark. So the questions do not come from me. The questions are coming from you.

Many of them already have. We're amazed at how many personal questions we've received about ovarian cancer during this program. Also, there are four experts with us, as I mentioned. And they come from a multidisciplinary approach here at Roswell Park Comprehensive Cancer Center.

And our first guest is Dr. Kunle Odunsi. Dr. Odunsi, thank you for being here. You're the Chair of the Department of Gynecologic Oncology here at Roswell Park, also the Executive Director of the Center of Immunotherapy, and the Co-leader of the Tumor Immunology and Immunotherapy Research Program here at Roswell Park. Again, thank you for being here. And in our conversations leading up to this, you said it's important to be aware of the risk of developing ovarian cancer. If you could talk briefly about the risk and the symptoms of this cancer.

Dr. Kunle Odunsi: Ovarian cancer is a disease that tends to affect post-menopausal women - women beyond menopause. But it can, in fact, affect a woman at any age. There are some risk factors that are well-defined. Again, age is one of them. The other is family history. Individuals who have a family history of ovarian and/or breast cancer appear to be at higher risk. And as we go on in this conversation, we will be talking more about some of these genetic risks.

The symptoms of ovarian cancer are not very specific. And that's one of the major challenges that leads to the majority of women being diagnosed at a later stage. Many of the symptoms are vague, such as abdominal discomfort, frequent urination, bloating, that will cause heartburn - these are symptoms that are vague that you really cannot ascribe to ovarian cancer. So if someone has any of these symptoms, the advice is to take them seriously and seek help as soon as possible.

Tim: I know we're going to have a lot of questions from folks that have already come in tonight. And we'll get to those in just a moment. To my left here is Dr. Kirsten Moysich. You're going to focus a lot on risk factors throughout this conversation. That's what you do. You're a Professor of Oncology here at Roswell Park. And also the Co-principal Investigator of the Ovarian Cancer SPORE Project and Co-leader of the Roswell Gynecological Cancer Disease Site Research Group. Thank you for being here--

Dr. Kirsten Moysich: --My pleasure.

Tim: Dr. Moysich. Thank you. Risk factors - talk a little bit about that.

Dr. Moysich: Well as Dr. Odunsi pointed out, age is, for most cancer, a significant risk factor, as is a positive family history. But more recently, we have recognized that personal history of endometriosis is a newly recognized risk factor. Historic use of talc use - not so much anymore. But way back - talc use - they added asbestos to the preparations. And that's why we think it's associated with increased risk of ovarian cancer. But fortunately, there are some protective factors - women having children early, having lots of children, breastfeeding their children. We recently learned that the use of aspirin - in particular, daily use of aspirin is associated with a decreased risk. And the most significant risk reduction factor is the - even short-term - use of oral contraceptives is associated with having a risk of ovarian cancer.

Tim: All right. Dr. Moysich. Thank you very much. And Mollie Hutton is with us tonight as well. Certified Genetic Counselor in the Clinical Genetic Service Department at Roswell Park. And Mollie, you say it's important to know and understand that genetic testing is widely open to ovarian cancer patients. Genetic testing. Small, little word, but it's a scary word. Talk a little bit about genetic testing and its availability to ovarian patients.

Ms. Mollie Hutton: Yes. Genetic testing is something that everyone should be aware of. And certainly, by way of knowing your family history, we'll be able to know whether you're a candidate for it. I think one of the biggest things that people should be aware of is that the change in guidelines that has occurred over the years - in the sense that, as of 2012, the National Comprehensive Cancer Network - or the NCCN - guidelines now indicate that any woman who's had ovarian cancer diagnosed - or their immediate family members - are candidates to be considered for genetic testing. And so having an awareness of your family history really can help indicate whether an individual or their family could benefit from pursuing this. And doing such, have a better understanding of what their cancer risk might be.

Tim: And again, a lot of specific questions for these folks tonight. We'll get to those. And they've come in already. And as they come in throughout the course of our conversation, one more panelist I want to tell you about - and that's Dr. Christopher Choi. You're excited about all the cutting-edge technologies that we can talk about tonight - the different therapies being developed right here at Roswell Park. Dr. Choi is an Assistant Professor of Oncology and Director of the Cell Production Facility here at Roswell Park. Tell me a little bit about some of these cutting-edge technologies, if you would.

Dr. Christopher Choi: So one of the things that we did here at Roswell Park is we developed the Therapeutic Cell Production facility - which is an actual laboratory following FDA regulations - being able to make drugs here onsite. So with that, we're able to take clinical or research taken from the lab bench top, into the clinic faster. And one of the therapies, or one of the clinical trials that we're able to develop led by Dr. Kunle Odunsi is a DC Vaccine clinical trial for solid tumors. Basically, it's a vaccine or something that boosts your immune system to recognize and fight off the cancer. And that's just one of the cool things that we're able to do here at Roswell Park with the Therapeutic Cell Production Facility.

Tim: All right. And one of the things that comes up when we talk about cancer all the time is the risk of recurrence. And certainly, there is a risk of that with any cancer and certainly with ovarian cancer. And Dr. Odunsi, this one is for you - from actually a couple of people that submitted two questions that I think are married together here. "How often does ovarian cancer recur?" And then part B, and someone else's question for this conversation is, "What treatment is recommended for recurrent ovarian cancer?"

Dr. Odunsi: Ovarian cancer is a disease that responds very well initially - so frontline therapies. Usually, we treat patients with surgery, very comprehensive surgery, followed by chemotherapy. The majority of ovarian cancer patients will respond and go into remission. Unfortunately, a significant proportion of the patients will ultimately relapse. And once relapse occurs, there are several treatment options that are available. Most of the treatment options right now involve one form of chemotherapy or the other. And there are several factors to be taken into account before selecting what is best for each individual patient. And I'm sure we'll come back and talk about clinical trials. But again, we encourage patients to participate in clinical trials - either to prevent relapse in the first place, or when relapse occurs, for patients to take advantage of novel, cutting-edge therapies, some of which Dr. Choi described earlier.

Tim: And we're watching that hashtag tonight, and that hashtag is #ovariancancertalk. If you're out there on Twitter, go ahead and use that. And that is how you can get a question in to us tonight. You can also go to roswellpark.org/ovariancancertalk, and also to the Roswell Facebook page, rather. And that is simply facebook.com/roswellpark. And that's where we get this next question that just came in. And Dr. Odunsi I'm going to stay with you for it. This person asking, "Does the use of oral contraceptives decrease the possibly of recurrence?"

Dr. Odunsi: Once ovarian cancer is diagnosed, the question is how do you minimize the risk of recurrence. And there are clinical experimental approaches that are going on. The use of oral contraceptives reduce the risk of developing the disease in the first place. There's no evidence that it reduces the risk of developing a recurrence. In order to minimize the risk of recurrence, most of the ongoing strategies involve one form of clinical trial or the other.

Tim: Thank you Dr. Odunsi. And Dr. Moysich, we're going to move over to you for this next question concerning detection and screening. This question coming in from one of our web viewers, "Are there any screening strategies for ovarian cancer to detect it early?" And then they go further in asking, "Is there anything specific for women with family history of ovarian cancer? And what if genetic testing was negative?"

Dr. Moysich: Yes, there are two screening tools for the early detection of ovarian cancer. And unfortunately, both have important limitations. One is a very clinical application, a transvaginal ultrasound, where the doctor just basically visualizes the pelvic area for evidence of disease. Unfortunately, through the visualization, the doctor cannot distinguish between benign ovarian disease or malignant ovarian disease, which is ovarian cancer.

The second screening test is a blood test for a marker called CA-125, which is elevated in most - but not all - patients with ovarian cancer. Unfortunately, it is also elevated in women with benign conditions, such as benign cysts, endometriosis, or liver disease, or sometimes elevated in women who are currently menstruating. So it's also a limitation that some women with ovarian cancer do not have elevated levels of this marker.

And in a very large study that looked at nearly 80,000 women, where women were assigned to normal gynecological care and screening with these two tools, there was no difference in the rate of ovarian cancer death between these two groups. And what this study also showed that, among the women who were screened, there were some serious complications as part of the follow up to the screening where the women had to be worked up. And so it was considered that screening in the general population caused more harm than benefits. Among women with a high genetic risk, which Ms. Hutton will address, there are currently two views - like one school of thought recommends very frequent screening with these two screening modalities. And other, in particular gynecological oncologists, recommend prophylactic removal of the ovaries after women are done with their child bearing.

Tim: We've heard a little bit about trials already. What are trials? And there's a lot of interest among patients with ovarian cancer in the trials that might be available. And Dr. Choi, you're the guy to answer this one. How do you do it? How do you choose patients to participate in trials once they raise their hand?

Dr. Choi: Well, that's a very good question. Clinical trials, in general, has to go through a very rigorous process, which is required by the FDA. And it goes through four phases. Phase 1 specifically addresses safety. Phase 2 addresses efficacy. Phase 3 - at that point your numbers increase. And with the increased numbers, you can see what side effects is this drug causing. You're also seeing if this drug is better than what's standard. And then, once it gets to market, you go through a Phase 4, which allows a post-market study, saying is there anything else we need to know about this drug?

So choosing patients for the different phases of the trials may vary. And with Dr. Odunsi's Phase 1 DC Vaccine Trial, there were inclusion and exclusion criterias that the patient first had to meet. And they also had to express something called NY-ESO-1. So that were some of the requirements for that clinical trial. In other clinical trials, patients, once selected, are randomized for treatment. So it really does vary depending on who's conducting the clinical trial. And what exactly are they looking for, for the treatment or for the drug itself. So there's a lot of variables.

Tim: The phrase "trial," I think is somewhat confusing to us laymen out there. Because really, these have gone through an incredible amount of testing, and these are very safe and effective approaches to other cancers. And obviously tonight we're talking about ovarian cancer.

Dr. Odunsi: Let me just make a couple of points there.

Tim: Sure, Dr. Odunsi.

Dr. Odunsi: And that's a very important point, that while the first trial might be of concern to some, these are studies that are done under very rigorous conditions. Before conducting a clinical trial, there's usually significant amounts of evidence, laboratory evidence, scientific evidence, that is generated to support the fact that this potential new treatment is likely to be better than standard therapy. So at Roswell Park, we have a large portfolio of clinical trials - either Phase 1, or 2, or 3 - such as the ones described by Dr. Choi - that we offer to patients, based on the best scientific evidence, and what we think would be best for each patient. So it's important to understand that clinical trials is not just giving somebody a placebo. It's really trying to still improve the outcome for each individual patient.

Tim: Right. And Mollie Hutton, back to you for this one that came in from our audience out there. "What is the benefit of genetic counseling and/or testing when family members have a diagnosis of ovarian cancer, if there is nothing that can prevent the cancer?"

Ms. Hutton: I think the most important thing that we try to do in genetics with genetic counseling and testing is to try to identify who's at increased risk. And try to minimize risk, reduce risk, or prevent a diagnosis from happening. And we meet with lots of individuals who have seen themselves have diagnoses, their relatives have diagnoses. And their whole goal they all express is, "I don't want my next generation to have to go through this as well. What can we do to try to improve things for the next generation?"

And so, with genetic testing, we're trying to identify - can we figure out what caused the cancer in the first place? Is there a hereditary aspect to it? And if so, who else in the family is at risk? And who's not at risk? And then through that, we can better identify what type of screening is appropriate. And as Dr. Moysich indicated, as we're talking about ovarian cancer, because we don't have screening tools that are quite as specific as for other diagnoses right now, we often do talk about things like risk-reducing surgeries once a woman's beyond child bearing, as a way to help prevent ovarian cancer diagnoses from occurring in the next generation in the family.

Tim: All right. Thank you. And we are watching the hashtag out there tonight. And we're watching Facebook. We're watching our website. And our next question comes in from that. And it is, "My mom had ovarian cancer. In being proactive, my ob-GYN is alternating the CA-125 blood test with an internal sonogram every six months. Do you feel that this is enough in the effort to be proactive?" Dr. Odunsi, I think that's for you.

Dr. Odunsi: Yeah. I think it's important to be proactive. And it's actually important to try and define the risk of ovarian cancer a little bit better, especially by going to the genetic counselor. And I'm sure, based on the discussions this evening, you've already heard that any woman with ovarian cancer, or if you have a family history of ovarian cancer, it's important to go for genetic counseling and see whether or not you want to undergo genetic testing. In fact, genetic testing is now recommended.

So that will allow the individual to make an informed decision about what to do next, whether to do something to prevent further development of ovarian cancer, such as lifestyle modification, the use of the birth control pill, or to consider risk-reducing surgery. So those are some of the options that are out there. But those decisions are better made in the context of genetic counseling.

Tim: All right. Thank you for that live question.--

Dr. Moysich: --And if I--

Tim: --And Dr. Moysich, do you want to follow up with that first? Go ahead.

Dr. Moysich: So that is reassuring to hear that the screening is very frequent. Because there's a very large ongoing study out of the UK that focuses on high-risk individuals. And very initial results have shown that very frequent testing - screening every four months is really the only way to detect ovarian cancer early. Yearly screening did not yield the detection of early ovarian cancer. And so, again, more frequent screening, if screening is being pursued, is probably the way to go.

Tim: Want to follow up with you, too, based on the question for Dr. Odunsi, and your follow up to that. We're throwing around the phrase C-125 - that marker. One of our viewers asking, "What is the CA-125 marker? And when is this test appropriate and helpful?"

Dr. Moysich: So, as I pointed out - it stands for Cancer Antigen 125. And that was developed in the 1980s with a kind of follow up, more useful marker developed in the late '90s. But the precise function of the marker is I think, at this point, is still unknown. We just know that it's higher in ovarian cancer patients. And as I pointed out before, it's probably not appropriate to use this as a screening tool for women at normal risk for ovarian cancer. And it remains to be determined whether - how useful it is in women with very high risk of ovarian cancer. But definitely, as I pointed out before, general population screening is associated with more harm than benefit. Because there's no difference in the death rates of ovarian cancer among women who are routinely screened, and among those who don't.

Tim: All right. And Dr. Choi, they are out there watching you and your work. And they're asking you tonight, "Can you describe the immunotherapy trial, preliminary results, and eligibility? Can it be used in recurrent settings? And are ESO-negative tumors eligible, too? Is preliminary data promising? There's a lot there in that question. But I think, in at least general terms, if you could address that theme.

Dr. Choi: Yeah. And again this is Dr. Kunle Odunsi. He was the spearhead and the lead and the Principal Investigator on this clinical trial. So I'll talk about it first, and then I'll shoot it over to Dr. Odunsi. So, in 2012, we developed this DC Vaccine Clinical Trial. And essentially using it in addition with rapamycin. The DC vaccine are - we take cells from a patient, and then we add a tumor antigen called NY-ESO.

So to address one of your questions earlier, for this particular clinical trial, we don't accept patients that are NY-ESO-1 negative. So then once we take these cells with the NY-ESO tumor antigen, we mix it together. It's like cooking right? And then what we do at that point is, we - again, this is outside of the body - we grow it up. And then we put something called - we mix it with - the patients get rapamycin. And this is thought to extend the immune response or the T-cell response within the patient. And then we give that back into the patient. So the clinical trial is almost complete. And I'll let Dr. Odunsi talk about the rest.

Dr. Odunsi: Yes. So the initial results from the clinical trial are actually quite promising. It's shown us that this vaccination approach is safe. That in fact, we can induce strong immune responses in the majority of the patients that have been treated. But the question is, what happens to NY-ESO-1 negative patients? And what happens to patients who relapse down the line where we need additional salvage therapies? Because the target on the cancer cells for the vaccine is found in only about 35-40 percent of ovarian cancer patients.

So we have developed other strategies to help patients whose tumors do not express the NY-ESO-1. An example of such an approach is to use some antibodies that we now know are able to take off the brakes from the immune system. So when you and I get an infection, the immune system goes after the bacteria or the virus. But at some point, the immune attack against the bacteria or virus has to stop. So that's like putting a brake on the immune system. What cancer cells have done is to hijack some of those exact same mechanisms by putting a brake on the immune system in order to escape from immune attack.

One of the strategies for patients whose tumors do not express NY-ESO-1 is simply to take off that brake, by manipulating the immune system using some antibodies, take off the brake, unleash the immune system. And now they can effectively attack and destroy ovarian cancer cells.

So those trials are ongoing at Roswell Park. And there are additional trials that perhaps we'll talk about during the course of this conversation.

Tim: All right, thank you. Hashtag #ovariancancertalk. That is what to look for out there on Twitter. And we have another question that has come in just that way. "Removal of the ovaries was just mentioned for a high-risk individual. Do you recommend such removal pre-menopause only or post-menopause?" Dr. Moysich, I think we're going to go with you on that.

Dr. Moysich: Well, I think that's a very personal decision. And it really depends on the woman. So it certainly depends on child bearing choices. If women have a wish to have more children, that should certainly influence the decision. And it really also depends on the severity of the risk factors - whether or not the woman has BRCA1 or BRCA2 mutations, the extent of the family history. And I don't think there's an easy answer for that. But obviously, it would be desirable to delay the surgery until a woman has all the children that she wants.

Tim: Okay. Thank you very much. And right back to the live questions that are coming in. For Dr. Odunsi this time, "Has anyone connected a mother's use of DES in ovarian cancer and her daughter? My mom took DES." And they're wondering about that.

Dr. Odunsi: DES is associated with certain cancers of the female reproductive tract. And fortunately, ovarian cancer risk - ovarian cancer is not one of them. But DES exposure during uterine life appears to be associated with certain cancers of the female reproductive tract. And I will say that, it really does not appear to increase the risk of developing the type of ovarian cancer that we're talking about.

Tim: All right. Thank you. And Mollie Hutton, next one is for you. And I think this is really a fascinating question in the day that we live in now. "Can I get denied from new insurance plans if I have BRCA testing and it was found to be positive?"

Ms. Hutton: So this is a very common question that we hear from a lot of our patients or would-be patients that kind of keeps them away from pursuing genetics. And I think the most important thing for everyone to realize, is that there is legislation in place to kind of protect against that and allay those fears for people. Basically, what the legislation exists - it's called GINA. It's Genetic Information Non-Discrimination Act. It protects against discriminatory situations in health insurance as well as employment, and indicates that a genetic test result cannot be used to determine your insurability. So you cannot be denied health insurance. You cannot lose your health insurance. You can't have premiums increase because of a genetic test result.

And so years ago, we had a lot of patients who chose not to pursue testing, or avoided even coming in to have a discussion about it, because of concerns about discrimination. And that's something that we really feel is not much of a concern anymore. It should not be the reason for somebody not to pursue testing at this point.

Tim: All right. We're halfway through our first conversation here. And tonight we're focusing on ovarian cancer. We are live from Roswell Park Comprehensive Cancer Center in Buffalo, New York. It's a multidisciplinary panel here that we've assembled, with four experts from various aspects attacking this disease head on. And we're talking all about ovarian cancer tonight.

If you have a question, you can submit it using #ovariancancertalk out there on Twitter. You can go to the Facebook website for Roswell Park, which is simply facebook.com/roswellpark. Or you can also use the chat feature at the roswellpark.org/ovariancancertalk website that you likely went to, to find this conversation tonight.

Dr. Odunsi, back to you for this one. "What kind of surveillance should I have after I finish my chemotherapy?"

Dr. Odunsi: The major risk following completion of chemotherapy is always the risk of relapse, which we talked about a little bit earlier on. So it's important to continue to follow up with the provider - the treating physician - in order to know whether the cancer is coming back or whether the individual remains in remission.

So in general, we utilize two modalities. Actually, three modalities. One is clinical exam. So it's important to go back for regular clinical exam, including a GYN exam, along with the use of the blood test CA-125, which we've talked about before. This is the one scenario where CA-125 works very well. It doesn't work so well for early detection, as we talked about earlier. But it worked very well for tracking the progress of disease, especially if the CA-125 was elevated at the time of diagnosis. So CA-125 blood test is the second thing that needs to be done. And finally, if necessary, imaging studies, especially CT scans.

Tim: All right. Dr. Choi, I told you that there was a lot of interest in trials. And we have another question concerning them tonight. "What trials are available here at Roswell Park and other places, if you care to mention? How do patients find out that kind of information?"

Dr. Choi: You can go to clinicaltrials.gov. And that has all active clinical trials here in the United States. But specifically here at Roswell Park - of course, Dr. Odunsi is one of the main people conducting these ovarian cancer clinical trials.

I mentioned earlier the DC Vaccine Trial. And my specialty is in cell therapy and manufacturing - cell therapy products following FDA regulations. One of the other clinical trials that we have is working with a biotech company. And essentially, unlike the DC Vaccine Trial, we are making your army of cells that recognizes the cancer. So you take a virus that expresses a T-cell - an engineered T-cell - that recognizes the cancer. So once you mix your cells with this virus that produces that cancer-recognizing T-cell receptor, then you put it back into the patient - and then those cells become armed and ready to fight off the cancer.

So I know this is a recurring theme. Once again, Dr. Odunsi is the PI of that clinical trial as well. And fortunately, I'm a co-investigator on that trial as well. So with that trial, we've already treated three patients here at Roswell Park. And other patients have been treated at other centers as well.

So that's one of the exciting new therapies that are being developed here at Roswell Park. And I think Dr. Odunsi can talk about the other non-cell therapy or even cell therapy clinical trials that you're a part of - have developed.

Dr. Odunsi: Yeah. So the program at Roswell Park has a broad portfolio of clinical trials, depending on where you are in the course of disease. Some patients will be undergoing treatment for the first time. Some patients will be in remission. Some will have relapse for the first time, go into remission again, and then relapse again. So depending on where a patient is in the history of their disease, there are trials almost at every point trying to develop the best strategies that will improve the outcome of the patient in terms of survival, as well as promoting their quality of life.

So some of the other trials that are non-cell-therapy-based include trials that we're doing in conjunction with the National Cooperative Group called the Gynecologic-Oncology Group - GOG. And there are also other trials that are developed at Roswell Park. Some of these trials are large, randomized trials. We have three trials whereby we are testing large numbers of patients across the country. Again, in order to identify the best way going forward.

Let me just give one example. There's a trial of a compound called a PARP inhibitor. This is a special drug that seems to be most effective in patients with BRCA1 or BRCA2 mutations. So that is a trial that is ongoing right here at Roswell Park. Again, the list of trials are available at clinicaltrials.gov.

Tim: All right. We're going to go back to trials in just a moment. We're going to switch gears briefly and go to Mollie. Mollie, someone writes to us that they had early stage ovarian cancer, "And I'm now in remission. I have a strong family history of many different cancers. What kind of testing should my teenage daughter have and younger sister have? What is the chance I will get another cancer?"

Ms. Hutton: So this is a very good question. And I think, again, knowing about family history is really important. And that's really the basis for trying to understand who else in the family is at risk and what are they at risk for. As it relates to this individual and this question, I think the most important thing for people to realize is that when approaching a family history and looking at doing genetic testing, the best way to ever do that is to first test somebody in the family who's already had a cancer diagnosis.

So to address this individual's question, really, that individual who's had the cancer diagnosis herself is the best candidate to pursue genetic testing. And through such, be able to provide additional information to her siblings and her children, and to understanding what their cancer risk may be, and what type of screening they may need. And the reason that we make that recommendation - and we also certainly understand, it's not always possible to test an affected family member.

But the benefit of that is that, in situations where we test unaffected individuals - if we don't find anything through that test, we don't know what that means. Does it mean their affected family member had a genetic factor associated with her cancer which they didn't inherit? Does it mean we're testing for the wrong thing? We're very limited in our ability to interpret that test report.

Whereas if we can first test somebody who's had a diagnosis, if we identify a genetic factor associated with their diagnosis, we now know exactly what to look for in their family members. And we know that in the family members who have the factor, they are at increased risk. And those who don't have it - it almost erases their family history for them to some degree. And would indicate that they are not at increased risk for the cancers associated with that condition.

Tim: A lot of interest from the viewers out there tonight in the family history, the trials, I think, and this whole genetic aspect of how ovarian cancer is being dealt with.

Dr. Moysich, question for you from our live web audience this evening, "Are there any specific diets that you would recommend for ovarian cancer patients and survivors? Are there any current dietary studies being done in this population?"

Dr. Moysich: Yeah, I wish I could tell you that a diet low in fat and high in fruits and vegetables would be protective for ovarian cancer or would be beneficial for survival for ovarian cancer. But kind of anticipating this question - because I get it a lot - I re-reviewed the literature and just read today a very recent review article. And in the conclusion it said there are no specific fat and dietary factors that have been linked to increased risk of or decreased risk of ovarian cancer. So there are a number of studies that have looked at diet and ovarian cancer risk. And they're kind of all over the place.

Having said that, in terms of identifying risk factors for ovarian cancer, we increasingly recognize that not all of ovarian cancer is created equal. We recognize that what might be a risk factor for one type ovarian cancer is not a risk factor for another type of ovarian cancer. And we might miss the subtle associations by sub-types if we lump them all together. So essentially, all of the studies that have looked at diet and ovarian cancer have lumped the sub-types together. And there's a lot of work to be done to really look at dietary risk factor among these important histological sub-groups.

Tim: All right. Again, live from our web audience out there tonight, as we continue our conversation about ovarian cancer from Roswell Park Comprehensive Cancer Center in Buffalo. Dr. Odunsi, "Faced with recurrence, would you recommend chemosensitivity assay to determine which treatment to try before selecting the gold standard which varies by oncologists?"

Dr. Odunsi: That's a good question. There are a number of drugs that are effective in recurrent ovarian cancer. And generally, patients and their physicians face sometimes a hard time - a challenging time - selecting what is the most appropriate next chemotherapy agent. The chemosensitivity assays may provide some additional information regarding which drug to choose. However, there's no conclusive evidence that the use of the chemotherapy assay is associated with better outcomes for patients. If the information is available, it may guide. But essentially what I'm saying is it's not cast in stone. It's not a test that has to be done prior to selecting the next best therapy. But if it's available, it's taken into account in selecting the therapy.

Tim: This next question, we'll probably stay with you, and then I think maybe merge over to some comments that we might have from Dr. Choi. "Having stage 3C, and recurring in a year, what time frame should one try to initiate a trial?"

Dr. Odunsi: Again, that's a good question. I think a clinical trial could be considered at every time frame - from the point of diagnosis, all the way to the time of remission, and to the time of first relapse. So at any of those stages, we generally present appropriate clinical trials that has the potential to help our patients.

Tim: All right. And Mollie, let's talk a little bit more about the genetics involved with ovarian cancer. One of our viewers writing this evening, "I have a strong family history of breast cancer, ovarian cancer, and prostate cancer. Cancer's in the family, but cannot afford genetic testing. I already had my ovaries removed. Should I have my breasts removed as well?"

Ms. Hutton: I think this is again, a common situation of the patients that we see and work with. And the first thing I want to comment to is the cost of genetic testing and coverage for such. I think it's very important to realize, when we're talking about genetic testing, there's not one test that fits all. There is a lot of different hereditary conditions that exist out there. Many of which overlap with diagnoses of ovarian cancer. We also know that there's very good coverage for genetic testing nowadays through insurance companies. And this includes Medicare and Medicaid having criteria for people to be covered for genetic testing.

And so essentially, whenever we meet with patients, we discuss the financial aspect of it, and explain that no testing is pursued until we are able to better understand and clarify what the financial situation is, and whether testing would be covered. And in some situations it's not covered. But certainly, a majority of times we are able to secure coverage for people to pursue testing.

In the absence of pursuing testing, or even in people who have pursued genetic testing and we don't find an answer to explain the diagnoses in the family, we always come back to and say, "Well, we need to base our recommendations and cancer risks on what has happened in the family." Which is why having a very good awareness and understanding of your family history is so important. We are able to say when we see certain diagnoses in a family, we will expect that family members are at slightly higher risk.

The problem with that is not knowing the degree of risk. And so making recommendations about risk-reducing surgeries becomes a little more tricky in that regard. Because we don't know how extreme the level of risk is for everyone. We really tend to more base screening recommendations based on a family history in the absence of a genetic diagnosis being able to be made.

Tim: CA-125 is coming up again among the viewers out there. And that's the next question. And Dr. Moysich, that might be one for you. "I had a normal CA-125 when they removed my ovary, and then found out it was cancerous. Should I have different testing since the CA-125 wasn't elevated?"

Dr. Moysich: Well, as I pointed out before, it is known that the CA-125 test is - the levels are only elevated in about 85 percent of women with ovarian cancer. It is just not a good diagnostic test. And probably also not a good test for monitoring treatment success for risk of recurrence. There is another test - HE4, which is combined with CA-125 - is also somewhat useful with monitoring disease progress, but for these women for whom CA-125 is not a good test, unless Dr. Odunsi tells me otherwise, there are very few alternatives.

Tim: The word "relapse" keeps coming up. The word "recurrence" keeps coming up. And some of you out there are noticing that theme. "You keep mentioning recurrence. Do patients always relapse? And at what percentage? Or is it stage dependent? Because I was Stage 1A at the time of diagnosis."

Dr. Odunsi: The risk of relapse is clearly stage-dependent. It's also dependent on the type of ovarian cancer. We now know that there are - ovarian cancer is not just one disease. Based on more recent studies, looking at the genetic signature of ovarian cancers, you can have a Stage 1 that behaves more aggressively than a Stage 3 from another patient. But in general - some of the general principles are as follows:

Stage 1 disease tends to do better. In fact the chances of cure for Stage 1 disease is more than 90 percent. Unfortunately, most patients do not present at Stage 1 disease. Most patients, in fact, present at Stage 3, where the chances of relapse is very high - as high as 70 percent - stages 3 and 4. So the stage of diagnosis is important. And then the type of cancer is also important. The type when you look under the microscope, or based on the genetic composition of the cancer cells themselves.

Tim: All right. Dr. Choi, side effects are something of interest out there for sure. And one of our viewers is asking right now, "Are there clinical trials about side effects of treatment? For example, chronic pain or blood clots - to associate that connection?"

Dr. Choi: You know, I'm not aware of it. I'm sure there are, but I'm not aware of it. That being said, within the clinical trial that you're performing yourself, side effects are of course part of something that you have to monitor and look and expect during the clinical trial. And in general, a majority of the time, once you're off the drug, the side effects decrease most of the time. So I would say that for - it's built into the clinical trial - the monitoring and the possible expectation of side effects.

But other than that, if anybody else - if my other colleagues have any--

Tim: --Well, actually someone just followed up with a question that--

Dr. Choi: --Okay.

Tim: --is somewhat related to that. We're going to stick with you--

Dr. Choi: --All right. Sure.

Tim: On this one. This just came in. "Do people have to pay for clinical trials? If I live in Canada, am I eligible for a trial here in the United States?"

Dr. Choi: Typically, for us, when we hold clinical trials, we do - it's either part of it is covered by insurance. And we generally have funding for a certain number of patients for the clinical trial. And that saying - so if we have 20 spots, those are the funded patients.

And I think this is really important. When you're talking about clinical trials - again, with the DC Vaccine Clinical Trials, we actually had over 7,000 respondents to be a part of that clinical trial for 20 spots. And that being said, there's a lot going on in the world in terms of something called medical tourism, where if you don't have a spot here, perhaps there's something else in another country where they don't exactly have the rigors that they do here in the U.S.

And I'd really like to emphasize for the clinical trials in the U.S., it really is rigorous. As Dr. Odunsi mentioned, we have to do pre-clinical testing. It has to - even here at Roswell, you have to go through a scientific review committee, an Institutional Review Board - an IRB. Then it has to go through the phases of the clinical trial. So I would say that doing clinical trials here in the U.S. - just be wary of that when looking to be a part of a clinical trial.

Tim: Really is interesting how many questions are coming into the conversation talking about family history. And Dr. Odunsi, I'm going to point this one at you. "What is the Familial Ovarian Cancer Registry?"

Dr. Odunsi: The Familial Ovarian Cancer Registry was established at Roswell Park Comprehensive Cancer Center in 1981 by one of my predecessors, Dr. Steven Piver. Dr. Piver had the foresight to establish a registry whereby individuals who have one or more first-degree affected relatives, where ovarian cancer is occurring more frequently than can be explained by chance.

And when this registry was established, it captured information from families from across the United States. It has now become the largest familial ovarian cancer registry in the world with almost 3,000 families, where you have actually two or more first-degree affected relatives. It has become a very rich source of trying to understand the genetic basis of ovarian cancer.

One of the interesting points that I would like to make is that, although we know that BRCA1 mutation is the most frequent mutation that you find in people who are at risk of ovarian cancer, we don't find it in 100 percent. So you can have a family where you have two, three, four members of the family have ovarian cancer, and yet they test for the gene - and they test negative. So the question is, are there other genes that affect - that determine the risk of developing ovarian cancer?

So this is an ongoing research effort at Roswell Park - taking advantage of this unique familial ovarian cancer registry. I will encourage anyone out there who has such a family, where there are two or more first-degree relatives that have been affected by ovarian cancer - I will encourage them to contact us so that they can potentially contribute to new discoveries about how genetics predispose to ovarian cancer development.

Tim: Dr. Kirsten Moysich, I think the next couple of questions I'm going to target you for. One came in earlier, before we went on tonight. And that is, "How are risk factors for ovarian cancer related to risk factors for breast cancer?" And then a question that just came in live off the web, "Does a woman have a higher incidence of ovarian cancer if she has had breast cancer?"

Dr. Moysich: So I'll take the second one first. Yes, a positive family history of breast cancer is a risk factor for ovarian cancer. And ovarian cancer and breast cancer do share risk factors for both the BRCA1 and BRCA2 mutations related to both breast and ovarian cancer risk. But in addition to these genetic risk factors, both cancers also share reproductive risk factors. So having children early, and having lots of children, and breastfeeding children, are protective factors for both breast and ovarian cancer.

Tim: Mollie, let's move to you and go back to the genetic side of things. "I had ovarian cancer and uterine cancer. Otherwise, there is no family history of cancer. My sister has LCIS of the breast, is she at risk for ovarian cancer, too?"

Ms. Hutton: I think to address her sister's diagnosis - first of all, LCIS has not been shown to be associated with any hereditary cancer syndromes at this point. So her sister's diagnosis itself is not a risk factor. However, the individual herself who's had a cancer diagnosis - certainly, anytime we see ovarian cancer as we've discussed earlier tonight, that is an indication for genetic evaluation being appropriate.

We also know any time we see an individual who's had more than one primary diagnosis, that's also a risk factor for potential hereditary risk to be present. And any time we identify somebody as having a hereditary cancer syndrome, we know that that may affect more than just them. And so certainly their family members may be at risk. And so this is again a type of situation where, that individual is a candidate for genetic testing or genetic evaluation. And I think this is a good point to again point out - there's not just one genetic test. It's not one-size-fits-all. And so it's really important that people who are pursuing genetic evaluation make sure they're doing it through very appropriately trained individuals. Because it is a very complex situation. Genetics is expanding rapidly.

And so as Dr. Odunsi talked about, is there other genes, other than BRCA1 and 2 associating with ovarian cancer risk? We know the answer's yes. We know that there's been a number of genes identified recently that are very suggestive of having association with ovarian cancer risk in a hereditary situation. However, these are genes that are still under study and researched, and are not ready to be taken to a clinical situation to be testing families for. But that doesn't mean that that's not going to come in the future. And so, again, pursuing genetics through a qualified individual will make sure that families are getting the appropriate testing at the appropriate time - to be able to use that information to really help their families.

Tim: I think there's a future in reporting for some of the people out there that are asking questions tonight, because they found many ways to ask I think the same question. And I think that tells me though that there's an awful lot of interest. So I'm going to ask this one. "My mother passed away from ovarian cancer at age 48. I am now 58. Should I have my ovaries removed?"

Ms. Hutton: I think this again lends a question - anybody who has a family history. We talk a lot about first-degree relatives. First-degree relatives are a mother, sister, or a daughter with an ovarian diagnosis. Those individuals are candidates for genetic testing. And so I think that's probably the best starting point to try to identify what's the level of risk - is a surgical approach appropriate for me - would be to start with a genetic evaluation. And then based on those test results, that's when we hand the individual back over to their physicians and say, "Okay, what do we take with that result? Where do we go from here in terms of making some of those decisions?"

Tim: Dr. Odunsi, this question I think is really interesting to anyone who knows anything about cancer. And we talk about the spread of the disease. "How quickly can ovarian cancer spread or metastasize?"

Dr. Odunsi: That's a very good question. But the answer is, "I really don't know." So we have seen patients who have a completely normal exam and develop ovarian cancer within a relatively short period of time. So somebody who goes for their annual GYN exam, for example - and everything is normal. In fact in some cases, the patient has had maybe an ultrasound, and everything appears normal. And within a relatively short period of time, the patient comes back with advanced ovarian cancer. So that is not unusual.

But the lead time for ovarian cancer from benign to malignant is totally unknown at the present time. And I think, as we develop more - as we become more sophisticated in developing early detection tests - we've said the CA-125 is not as useful as an early detection test - this will allow us to be able to define exactly what the lead time is for developing ovarian cancer. Right now we really don't know the lead time or how quickly it spreads to other organs.

Tim: How's that for a quick hour, everyone? There were a lot more questions. A lot more questions came in to us before this evening. And a lot more questions continue to come in. Here's the good news. We're not releasing them. They're going to hang around. They're going to help answer some of these questions. And all you need to do is watch the Roswell Park Twitter feed. You can also check out Facebook - facebook.com/roswellpark. And then watch for the posting of answers to the numerous questions that are coming in - the dozens of questions that continue to come in at roswellpark.org/ovariancancertalk.

I'd like to thank the panelists for being here tonight - truly a multidisciplinary approach - very interesting to get it from all the different aspects that there are available here at Roswell Park. Dr. Kunle Odunsi, thank you so much for your time. I appreciate it.

Dr. Odunsi: Thank you. You're welcome.

Tim: And by your side, is Mollie Hutton. Mollie, thank you so much. And Dr. Kirsten Moysich. And Dr. Christopher Choi. Thank you very much.

Dr. Choi: No problem.

Tim: Once again, please remember, all of the questions will be answered. You'll find that at roswellpark.org. Thank you very much for joining us. And we hope to do this again very soon.