March 2014 Research Highlights

Jamie DePolo: Hello everyone, and welcome to the Breastcancer.org podcast. I’m Jamie DePolo and I’m the managing editor of Breastcancer.org, and today it’s a Research News roundup podcast and I’m joined by Dr. Brian Wojciechowski, Breastcancer.org’s medical adviser.

Hello, Dr. Wojciechowski, how are you today?

Dr. Brian Wojciechowski: I’m fine, Jamie, how are you?

Jamie DePolo: We have a very interesting group of Research News stories to talk about today. They are kind of all over the map, to exercise, to sex, to paying for your care, to some new guidelines from ASCO and ASTRO. So since we’ve got six stories to cover, I think we should just jump right in so we can get everyone the latest information.

The first story we have is one that sort of re-emphasizes something that we already knew, but it’s always important to hear it again, and that’s the fact that daily exercise reduces the risk of breast cancer. And now, I know that this isn’t new news and we’ve seen several stories like this before. What can we tell people, or is there anything different about this study or this is the same thing, just in a different shape, different package?

Dr. Brian Wojciechowski: Well, this is certainly the biggest study that I’ve seen on the subject. You’re talking about 37 studies combined into one here with four million women involved and 114,000 cases of breast cancer. So if there was any doubt in anyone’s mind about the value of exercise for preventing breast cancer, this study should really lay all of that to rest. It was a pretty significant benefit at 12% lower risk of breast cancer and well, if you take that and combine it with all the other non-breast cancer benefits of exercise, it presents a pretty compelling argument in favor of something we already know and of something we as doctors always try to emphasize with our patients and which cannot be under-emphasized is the importance of getting regular exercise.

Jamie DePolo: Definitely. I know for a lot of people who work outside the home, who work maybe two or three jobs even or who have small children, time is a really big constraint on exercising, and one of the things we recommend on the site is trying to break up your exercising to maybe 20- or 30-minute chunks. So maybe you have time to do a 20-minute walk in the morning, or maybe you get to take a 20-minute break at work and you walk, and then maybe you walk a little bit more after work with a friend. Because research has also shown that if you make plans to exercise with a friend you’re accountable and you’re more likely to do it. And, as a lot of ads have said, the most important thing that this research shows is that you have to just do it.

You have to get out there and you have to do something and walking is really easy, all you really need is a pair of sneakers and you can start slowly. Maybe you can’t do 30 minutes a day right at the beginning, but maybe you can do 5 or 10 and you work your way up. The important thing is to do something. So we just keep getting more and more evidence that exercise really does help reduce risk, and as you said, it also gives us so many other benefits for our general overall health. So we’re hoping that everyone out there is doing some sort of exercise every day, right?

Dr. Brian Wojciechowski: Yeah, and it doesn’t have to be all at the same time, you know, if you’re getting a 15- or 20-minute walk with the dog in the morning and then maybe go out on your lunch break and when you get home take a walk in the evening, that counts just as good as doing it all in 1 hour, for example.

Jamie DePolo: Sure. Okay. Our next study is a little more technical. This is research on some new guidelines for tumor margins and this came out from ASCO, which is the American Society of Clinical Oncology as well as ASTRO, which is the American Society of Radiation Oncology. And together, those two groups put together a group of experts and they said that tumor margins -- and this is when a lumpectomy is performed and the surgeon always tries to get a rim of healthy of tissue around the cancer that’s removed, and there have been some varying discussions on how wide that rim of healthy tissue needed to be. But these new guidelines say that they only need to be wide enough so there’s no ink on the tumor. And for all of us who aren’t surgeons, Brian, if you could explain what that means.

Dr. Brian Wojciechowski: Yeah. So whenever you remove the cancer from the body, you want to make sure, first of all you got all the cancer cells. So, you know, a positive margin can be anything where the cancer cells go right to the edge of the sample and you think that there’s probably cells left over in the body, or even… and this is where the controversy exists.

Let’s say you do get all the cancer cells out, but there’s only a millimeter or two of healthy tissue in between the tumor and the end of your sample, that’s what I would call a close margin, and there is some controversy over what constitutes a close margin. You know, some physicians have said, if you’re 1 millimeter there, if your margin is only a millimeter, that’s too close for comfort.

So many of the women getting lumpectomies have to go back in for a re-excision and, Jamie, you can imagine that this is a very stressful event in the course of a women’s breast cancer treatment to go, to get mentally prepared for surgery and go through all that and then to be told you have to go back and get a second operation, really….

Jamie DePolo: Because we’re not sure we got it all. That’s pretty scary.

Dr. Brian Wojciechowski: That’s right. It’s pretty scary and pretty stressful for a patient, and also it delays the time to when a woman can get her systemic treatment, like chemotherapy or hormones, or even radiation.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: So this is not an ideal situation where we’re going back and doing another operation.

Jamie DePolo: Okay. And now these new margins, or these new guidelines, excuse me, if I’m understanding them correctly, it says that a millimeter of margin is okay as long as there is no ink. And from what I understand, when the surgeon removes a tumor, a cancer, it’s then rolled in some special ink so they can see which cells are cancerous and which cells are healthy?

Dr. Brian Wojciechowski: Yes. Well, it’s not quite like that.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: What it is, is they take the tumor and roll them in ink, and then the tumor goes to the lab and gets sectioned. So it gets cut into very small pieces, and when you look at the cells under the microscope after a very, very thin slice of the tumor has been made, you can then see the ink that was put on the sample at surgery. So if you look under there and you see that there’s ink on the tumor cells themselves, you know that at the edge of the that sample the tumor cells were sitting there. So there would be a very good chance that you left some tumor cells in the breast that you took it out of.

Jamie DePolo: I see, I see. Okay. So these new guidelines then are saying as long as there is no ink on a tumor cell, no matter how small that margin, it’s okay.

Dr. Brian Wojciechowski: Yes, and also no matter what the biology of the tumor, whether it was triple-negative or HER2-positive, or ER-positive, that it doesn’t matter. So as long as you’re looking under the microscope and you’re seeing that there is ink and then next to the ink there’s healthy cells and then, next to the healthy cells there’s tumor cells, that’s okay, even if it’s under a millimeter, and that the woman does not have to go back in for another surgery.

Jamie DePolo: Oh, that’s good. So it sounds like this will sort of clear up, or standardize, I should say is a better term, standardize what people are looking at as far as margins and may save a number of women from having surgery.

Dr. Brian Wojciechowski: I think that is the bottom line, Jamie, and if these guidelines are widely accepted and incorporated into practice, then definitely many, many women who otherwise would have gotten another operation will end up not getting that second operation. I know that my institution is looking at these very closely right now and will probably be changing our practice pretty soon.

Jamie DePolo: Okay. Because these two institutions, ASCO and ASTRO, are both very well known and very esteemed, professional organizations, so when they put out guidelines, almost everybody pays attention.

Dr. Brian Wojciechowski: Exactly.

Jamie DePolo: Okay. Okay. Great. So that’s some good news. Our next study is not so good news. Research was done on the economics of paying for treatment, and it was found that about a quarter of the women who are diagnosed with breast cancer go into debt to pay for their treatment. And some of them said they had to give up their home, some of them said they were doing without things, like they weren’t paying their utility bills because they needed to pay their medical bills. All of which is very disturbing and upsetting, because people should have access to care.

Dr. Brian Wojciechowski: That’s exactly right. And we know, I’ve seen it in my own practice, and financial problems can interfere with care, and you can delay the time that it takes to get the right treatment, and even affect her ability to continue on her treatments. So it’s a big problem.

Jamie DePolo: Yes, and we know, we’ve see other studies, too, where it says if you delay your treatment longer than a certain number of days it can affect survival, recovery, recurrence, all sorts of things. So while the study just sort of lays that information out there it doesn’t really offer any way to change that. And what we suggest on our site, we have a section called Day-to-Day Matters and under Day-to-Day Matters there’s an area called Paying for Your Care. And there are all sorts of links and information about what to do if you are having problems paying for your care.

Most of the big pharmaceutical companies have assistance lines that you can call if you’re getting a specific treatment that you can’t afford. You can contact the company that makes it and they will almost always have an assistance line or an assistance program that you can get into that will either help you pay for the medicine or give you a significant discount.

There are also links and information to other groups that help people pay for their medical care. So the bottom line is, check out those links, ask your doctor for information, and ask your local community services organizations for information, because you do need to get that care and it should not be a financial burden. So please, please check out that information on our website.

Dr. Brian Wojciechowski: Yeah, and don’t be ashamed to seek help.

Jamie DePolo: Definitely, it’s not a shameful thing.

Dr. Brian Wojciechowski: Right, and most people are very eager to help out financially, family members, that sort of thing. So yeah, really important issue.

Jamie DePolo: Definitely. Now, the next study we’re going to look at focused on older women who had survived breast cancer, I believe they had been diagnosed about 10 or 15 years beforehand, and it was looking at some sexual issues. And we know, at least from the topics on our Discussion Boards, as well as some of the posts on our Facebook page, that sexuality issues can be a big problem for some women during diagnosis, through treatment, and even after treatment. They’ve said there is less interest in sex, sex may become painful, and this study was kind of looking at all those things, and it found that while older survivors were having less sex compared to women who hadn’t been diagnosed, the problems they reported were about the same.

So in a sense, I guess I kind of want to look at the silver lining here, it’s a little bit encouraging to know that women who had been diagnosed with breast cancer don’t have different sexual problems than other older women. I guess that’s one encouraging thing. Although, the study itself is saying that older women who had been diagnosed were having less sex, that’s a little bit disappointing and could be upsetting, and, again, this study just kind of just looked at the facts, it laid it out there and didn’t really say, okay, what do we need to do to solve this problem?

Dr. Brian Wojciechowski: Well, I think with this particular issue it’s awareness that is the first step, because this is something that many women are not comfortable bringing up and many doctors are not comfortable talking about with their patients. So I think we could do a lot to help by just being aware of it and not hesitating as physicians and patients to bring these issues up.

Jamie DePolo: And, certainly, there are doctors who specialize in these issues, so if, as a women, you don’t feel comfortable talking to your oncologist or maybe your regular doctor, ask for a referral. Again, you’re not going to get help unless somebody knows there’s a problem. So you don’t have to go into a lot of specifics, but you can just say, “I’d like a referral to a doctor that specializes in some of these issues,” and I’m sure most physicians would be happy to give that referral.

Dr. Brian Wojciechowski: Yeah. Life goes on, Jamie.

Jamie DePolo: All right. Let’s see, now, our next study, again, this study, I believe, the results have the potential to be practice-changing. It was looking at whether or not radiation was beneficial after mastectomy, and this in women who it was found to have one to three positive lymph nodes. I guess before we go into it, Brian, if you could just explain it to us again, what does it mean to have a positive lymph node.

Dr. Brian Wojciechowski: So, with mammograms today and screening, most of the breast cancers we diagnose are early stage and are not yet in the lymph nodes, but the first place that a breast cancer usually spreads when it spreads outside the breast is the lymph nodes under the armpit. So that’s what we refer to when we talk about a positive lymph node, that’s when the cancer has spread to the lymph nodes under the armpit.

Jamie DePolo: Okay, and I know there’s been some controversy. Some results of earlier studies showed that radiation after mastectomy was beneficial if there were one to three positive nodes and some showed no benefits. And in the past, I guess, it’s sort of commonly thought that if a woman had a mastectomy it was pretty much unlikely that she would need radiation because the entire breast was being removed.

Dr. Brian Wojciechowski: Yeah, but let’s make a distinction between radiation to the breast alone and radiation to the axilla.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: So, yes, typically, when a woman is deciding between mastectomy, which is removal of the whole breast, versus lumpectomy, just getting the tumor removed, she might be factoring in that not needing radiation if she gets the whole breast removed. And that’s true, when you have the breast removed you generally don’t need radiation to the breast, or, I should say, to the area that was left behind. But when a doctor does a mastectomy, she’s looking at the lymph nodes and seeing if there is any cancer there. And if there’s more than four nodes involved in the armpit, then it’s definitely a no-brainer, you have to get radiation to that whole area.

Where the controversy exists is, what if there’s only one to three nodes that are positive for cancer, and that’s where the practice has not really been uniform. Some women at that point will get radiation, some will get a full dissection, where they take all the lymph nodes out. So that’s an area of controversy, and, you know, if a woman is getting lymph nodes removed surgically and radiation to that area, there’s certainly going to be a higher risk of lymphedema, a higher risk of cancers later in life, decades later, which we know is a risk with anyone getting radiation.

Jamie DePolo: Okay. This study was trying to clear up that controversy, and it seems like it did in that it was a meta-analysis, so it was looking at a lot of the earlier studies, and it found that if there are one to three positive nodes then radiation is beneficial.

Dr. Brian Wojciechowski: That’s right. This study did not identify a group of women with positive lymph nodes that didn’t benefit from radiation. So the suggestion here is that, even after mastectomy, any women with any positive lymph nodes should have radiation to the axilla. Now, here’s the bugaboo about this study. The latest group of women that were enrolled in this trial started in 1986. So, you know, the women studied in this trial received their diagnosis and surgery anywhere from 1964 to ’86, and then were followed over time. So, you know, that’s an eternity in terms of breast cancer treatment.

For example, since 1986, chemotherapy has improved, hormone therapy has improved, surgical techniques have improved, and yes, radiation techniques have improved, as well. So, you know, with better hormones and better chemo and better surgical techniques, we are going to eliminate a lot of the late recurrences anyway. So it’s hard to see exactly how this applies to our practice today.

So while it does have the potential to change practice, or at least to suggest a modern study should be done, I’m not sure if this really fully clears up the controversy about women with one to three positive nodes after mastectomy getting radiation or not. I can tell you one thing though, it will spur a lot of debate.

Jamie DePolo: Okay. So in your hospital and practice, you’re not necessarily going to change what you do, but you’ll be looking at this study and kind of waiting to see if another study is done?

Dr. Brian Wojciechowski: Well, I think I’m going to take this into account, but I don’t think it’s going to make me automatically say that every woman with one to three positive nodes after mastectomy should get radiation. I think we’re giving some of those patients radiation, some of them are getting lymph node dissection, and we leave it at that. You know, it definitely gives me pause and I will definitely consider the results of this study, but I don’t think it’s practice-changing at the moment.

Jamie DePolo: Okay. That’s good to know. That’s good to know, and certainly anyone who is diagnosed and the pathology report comes back and shows that, that’s something to discuss with your oncologist, with your surgeon, and take into account your personal preferences as well.

Dr. Brian Wojciechowski: Yeah, and especially the radiation oncologist.

Jamie DePolo: Okay. Yeah. And then, our last study to talk about today, there’s an experimental medicine called palbociclib and research came out -- now, this was a phase II study, which makes it an early study, it’s not necessarily going to be on the market soon, or tomorrow, I should say, it’s going to be several years -- but it found that the combination of palbociclib and Femara, which is a hormonal therapy, was improving progression-free survival of advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer. And, Brian, if you could talk a little bit about, before we get into the specifics of the research, what exactly is progression-free survival, and I know there’s been some controversy over whether improving that is enough for a medicine to come to market.

Dr. Brian Wojciechowski: So, the gold standard for efficacy of a cancer drug is overall survival. And if a drug has an overall survival benefit, that means that the women who took the drug actually lived longer than the women who did not take the drug.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: And it’s self-evident why that should be the ideal.

Jamie DePolo: Sure.

Dr. Brian Wojciechowski: Now, some drugs are shown to improve progression-free survival and not overall survival. So that means that for the women who took the drug, they went longer without their cancer growing or needing a new treatment than women who did not take the drug, but in the end, there was not difference in when those women died. So they didn’t live any longer, they just lived longer without their cancer progressing.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: And you know you could ask, if the women lived longer without the cancer progressing, why did they not live longer overall and the reason is complicated. It may be that the drug just doesn’t make you live longer, so that’s one possibility. The other possibility is that these women are women with metastatic breast cancer and they will have seen many different treatments during the course of the disease, not just the study drug. And many studies include something called crossover, where even if a women does not get on the arm in the study where you get the drug initially, she could be eligible to get the drug later, when she progresses.

So it’s possible that that woman catches up with the women who get the drug in the front line and end up living the same amount of time overall. So, you know, just because a drug does not improve overall survival doesn’t mean it’s not effective, because it can still improve progression-free survival. You know, I think that would matter to a woman with stage IV breast cancer, to be alive longer where her disease is not progressing and she doesn’t have to switch her medication, even if at the end she’s living the same amount of time.

Jamie DePolo: Sure. And this was phase II study, which means that it’s looking at how effective the drug is, is that right?

Dr. Brian Wojciechowski: Yeah. Well, there’s basically three phases. Phase I is where you’re giving the drug to women who really have no other option, and you’re giving them different doses just to see what the safe dose is, so really not an effectiveness study.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: Phase III is the opposite end of the spectrum where it’s a large number of women and they’re randomized to an arm where they get the drug and they’re randomized to an arm where they don’t get the drug, and you’re comparing the outcome. So phase II is sort of somewhere in the middle. You know, sometimes phase II studies can have two arms, where one arm gets the drug and one arm does not. Sometimes they have just one arm, but they’re usually bigger than phase I studies and they’re smaller than phase III studies, and the safety and effectiveness of the drug is usually already established by the time you get to phase II. But typically, the regulatory organizations like the FDA are going to want to see phase III data before they approve a drug. There have been exceptions and this drug could be an exception, but we’re all going to kind of be waiting on the edge of our seats until they make their decision.

Jamie DePolo: Okay. From what I understand there are phase III trials underway for palbociclib, combining it with Femara and then also, I think, Faslodex, which is another type of hormonal therapy.

Dr. Brian Wojciechowski: That’s correct.

Jamie DePolo: Okay. And so if anybody out there listening is diagnosed with advanced-stage, estrogen-receptor-positive, HER2-negative disease and you’re kind of running through the standard treatments -- maybe the disease has stopped responding to those and you’re interested in potentially trying this -- you would have to be in a clinical trial to be given palbociclib right now. And the best way to figure out that is you can talk to your doctor and see if there are clinical trials in your area that might be a good fit, or you could go to the Breastcancer.org website and under the Treatment tab, we have a section on clinical trials and you could go to the government website and figure out where they are.

Usually, phase III trials are very large, hundreds of thousands of women, and they’re done in several sites. Sometimes even internationally because the regulators really want to be sure that whatever this new medication is, that it’s better than what we have now. Because I know in talking to some researchers who work on drug development, if there’s a medicine out there that maybe is just as good as what’s out there now, it may not necessarily get to market because it’s not better and there’s no real incentive to get it out there.

Dr. Brian Wojciechowski: That’s exactly right and it’s usually a lot more expensive than the….

Jamie DePolo: Because things that have been out for a while like tamoxifen, they’re generic, so they’re less expensive for the patients to buy, so it’s the new stuff that’s still on patent that’s much more expensive. And certainly when palbociclib, if it does get approved by the FDA, then it would probably be more expensive than some of the curtain standard treatments. But still, it’s very exciting, always good to be finding new treatments for advanced-stage disease because a lot of research effort goes into early-stage disease and I know sometimes people diagnosed with advanced-stage feel like there’s not a lot of treatments for them out there. So this is pretty exciting news and again, if this medicine might help you, you would have to be in a clinical trial and you need to talk to your doctor and figure out if there’s a good fit for you.

Dr. Brian Wojciechowski: Yeah, and this drug has a potential to create a very big impact. I mean, three different companies right now are working on a version of this drug with, this drug is made by Pfizer. With Pfizer’s drug sort of being in the lead right now, the benefit was preliminarily, it looks pretty striking and it has the potential to have a huge impact because the indication is frontline metastatic disease. So any woman with stage IV disease beginning her treatment, which is about 50,000 women a year in the United States, would be eligible to take this drug in combination with Femara when it gets approved. And it is targeted therapy, so it’s not chemo, and it is a pill, so it’s not an IV drug, and the side effects are pretty manageable. So we’re going to keep a very close eye on this drug and its trek through the approval process, because it’s very exciting and potentially would have a very big impact.

Jamie DePolo: Sure. Now, have you heard anything about palbociclib being fast-tracked for a faster approval? I have not, but I just wondered if you had?

Dr. Brian Wojciechowski: No, but of course, there’s a lot of speculation.

Jamie DePolo: Okay. Well, we’ll definitely keep everyone updated on that if we hear anything else. Is there anything else you want to add on these studies, Brian?

Dr. Brian Wojciechowski: I think that’s all I have, Jamie.

Jamie DePolo: Great. Well, thank you everybody for listening. This has been the Breastcancer.org podcast, our Research News roundup for the month of April. Our medical expert, Dr. Brian Wojciechowski, gave us his excellent comments on what’s going on. We hope you all tune in and again, thank you for listening.

Dr. Brian Wojciechowski: Thank you.

Editor’s Note: On Feb. 3, 2015, the U.S. Food and Drug Administration granted accelerated approval for using the targeted therapy Ibrance (chemical name: palbociclib) in combination with Femara (chemical name: letrozole) to treat advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer that hadn’t been treated with hormonal therapy before in postmenopausal women.