Research Highlights From the San Antonio Breast Cancer Symposium, December 11, 2013
Brian Wojciechowski, M.D.
December 11, 2013

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In our premiere podcast, we're excited to bring you a summary of the day's research highlights from the San Antonio Breast Cancer Symposium 2013! We discuss treatments before surgery for HER2-positive cancers, radiation after lumpectomy in women over age 65, and more. Breastcancer.org medical adviser Brian Wojciechowski, M.D. and senior editor Jamie DePolo explain the latest news.

Running time: 26:14

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Jamie DePolo: Good evening, everybody. This is Jamie DePolo. I’m the senior editor at Breastcancer.org, and I’m down here in San Antonio at the San Antonio Breast Cancer Symposium with Dr. Brian Wojciechowski. He is Breastcancer.org’s medical adviser, and we’re going to talk about some of the research we saw today during the sessions. It was very informative, very exciting. Several things we saw we think have applications for people diagnosed with breast cancer today, things that you can talk to your doctor about, and there are also some things that are exciting but are a little bit further down the road. So we’ll talk about all those things.

The first research we’re going to talk about involves HER2-positive cancers and giving chemotherapy before surgery, which physicians and researchers call neoadjuvant chemotherapy. So, Brian, what did you think about that study? I believe it was the Neo ALTTO study, is that correct?

Dr. Brian Wojciechowski: Yes. It’s called the Neo ALTTO study, also called BIG 1-06, and this study looked at using the combination of lapatinib and Herceptin in the neoadjuvant setting in women whose breast cancer was positive for HER2. I guess I should talk about what neoadjuvant chemotherapy really is.

Jamie DePolo: Yeah. Why would somebody get that, and can you tell me too, just refresh my memory, what’s the brand name of lapatinib? What do we call it?

Dr. Brian Wojciechowski: So lapatinib is Tykerb.

Jamie DePolo: Tykerb. Okay.

Dr. Brian Wojciechowski: Yes.

Jamie DePolo: Some people might be more familiar with it that way rather than the chemical name, just to keep everybody on the same page.

Dr. Brian Wojciechowski: Yes. It’s actually a pill form of what we call targeted therapy, as is Herceptin, but Herceptin is intravenous. They both target different spots on the HER2 protein.

Jamie DePolo: Okay. So both medicines are used to fight HER2-positive cancers.

Dr. Brian Wojciechowski: Yes, and they’re not chemotherapy in the classical sense.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: So, neoadjuvant chemotherapy is also called preoperative chemotherapy, and the reason a woman might want to get neoadjuvant therapy is that if her cancer is higher risk, say greater than 2 centimeters or is present in the lymph nodes under the arm, getting chemotherapy before surgery can increase the chance that she could, for example, keep that breast and also increase the chance that the surgeon would get a negative margin; that is, get all the tumor out on the first try, and the woman may not need to go back for a re-excision.

Jamie DePolo: So a woman could have a lumpectomy instead of a mastectomy, even though the cancer is considered aggressive or has a higher risk of coming back or recurring.

Dr. Brian Wojciechowski: Exactly, and I think the important thing for the patients listening to this podcast is that the pattern usually is mammogram, biopsy, surgery, and then chemotherapy. There’s been a lot of excitement and a lot of studies in the last few years about preoperative chemotherapy, and it may not be on the radar screen on all the docs I the community, so it may be helpful if woman talk to their doctors about preoperative chemotherapy. You know, "Is this something that I should consider?"

Jamie DePolo: Okay, and it wouldn’t be necessarily that getting chemotherapy before surgery is appropriate for everyone. We would have to have some of the factors that you just talked about, in other words high-risk, aggressive cancer, perhaps HER2-positive, larger cancers. So those would be the kinds of things people would look for and then possibly consider the treatment before surgery.

Dr. Brian Wojciechowski: That’s right. You wouldn’t want to do it in very early-stage cancers, like cancers that are under 2 centimeters or cancers that are small and did not travel to the lymph nodes.

Jamie DePolo: Okay, and if I remember correctly, one of the interesting things about the study is they were looking at a measure called PCR, or pathologic complete response, and could you explain that a little bit for us?

Dr. Brian Wojciechowski: So, when you do chemotherapy before surgery, if the pathologist finds no remaining cancer in the breast or the lumpectomy after the surgery, that is a pathologic complete response. In other words, the chemotherapy made the cancer melt away completely.

Jamie DePolo: So it’s totally gone?

Dr. Brian Wojciechowski: It’s totally gone. Even before surgery, the cancer was totally gone.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: And when the surgeon goes in and takes it out, they don’t find any tumor.

Jamie DePolo: Let me ask you this, what do they actually go in and take out if there’s no tumor there? Do they just, from the previous imaging, they try to know where the spot was and they go in and look at that?

Dr. Brian Wojciechowski: Usually they leave a little marker in there.

Jamie DePolo: Okay. Okay.

Dr. Brian Wojciechowski: And the surgeon will take out the area around the marker.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: And why is this important? Well, there’s been a lot of studies in the past showing that when this happens, when you get a pathologic complete response, women do better in the long run. They tend to live longer, and it’s really the ideal outcome. So one of the important things about this study, the Neo ALTTO study, was that it shows that pathologic complete response correlates well with overall survival in the women whose tumors were HER2-positive but ER/PR negative; that is, estrogen/progesterone-receptor-negative. They didn’t really find a difference in the women whose tumors were ER/PR-positive, and that’s probably because those tumors are a little more indolent, grow a bit slower, and may take more years of follow-up to find the difference. This study only went out to 4 years.

Jamie DePolo: Okay. So only 4 years of thought, so it’s still relatively young. They’ll probably be following these women for a longer time?

Dr. Brian Wojciechowski: Yeah. They’re going to follow for many more years, and 4 years is really too young to draw solid conclusions. So this study is really not practice-changing at the moment, but I think for our listeners it’s important for them to realize that they don’t just have to get chemotherapy after surgery, that getting it before surgery may be a good option.

Jamie DePolo: Okay. So the bottom line might be if you know that you’ve been diagnosed with a cancer that is aggressive, large, it may be a good idea to at least bring up the subject with your doctor and ask, “Is this a good fit for me?” whether its chemotherapy or a targeted therapy before surgery to shrink the tumor down as much as possible or perhaps make it go away completely.

Dr. Brian Wojciechowski: Yes, and make it so there’s a better chance of keeping the breast.

Jamie DePolo: Okay. Okay. That sounds good, and then there was another study that we wanted to talk about. This one was about radiation after lumpectomy, and I believe this was the PRIME II study, a study that was done around the world, not in the U.S. (there weren’t any sites in the U.S.), but it was looking at older women, 65 and older, who were diagnosed with very early-stage, very sort of low risk cancer, so we're kind of spinning the whole thing around from the Neo ALTTO study. And the researchers were curious as to whether these women could actually skip radiation after lumpectomy. And we know that radiation plus lumpectomy is just as effective as mastectomy in treating early-stage breast cancer, but for some of these older women, can they skip it? What were these results and what was your reaction?

Dr. Brian Wojciechowski: I think this is a reassuring study, and what it tells us is that not having radiation for certain older women is a legitimate option. Now, there are a few caveats here. Number one, these women have very low-risk breast cancers, so radiation or no radiation, there’s a very low chance that the cancer would come back. For example, the women in this study who did not get radiation to the breast had about a 4% recurrence rate in the same breast, which is pretty low.

Jamie DePolo: That’s four women out of 100 to put it in terms…

Dr. Brian Wojciechowski: Yeah.

Jamie DePolo: Okay.

Dr. Brian Wojciechowski: Yeah. So even if they didn’t get radiation, only four women out 100 had the cancer come back in the same breast. So, this does not apply to women whose cancers are say, HER2-positive, which increases the risk; whose cancers are large size; whose cancers have spread to the lymph nodes; or women who are ER/PR-negative or triple negative. This really does not apply to those high-risk patients.

Jamie DePolo: Right, and the women did have to be 65 or older, correct?

Dr. Brian Wojciechowski: Yes. Yes. Exactly, and I just want to say one thing about a 65-year-old woman today in the year 2013. Now, in my practice, I’m in a community in a suburb of Philadelphia, I think the average age of my patients is over 65, and a 65-year-old lady today is not an old lady. Okay? Many of my patients are still working, are still very active, and you have to understand that a woman who's 65 and in good health has a really good chance of being alive at age 85. And this study really does not go all the way out to 10, 20 years, and the problem with that is that some woman will recur at that later date.

So, I think if I were a radiation oncologist talking to my patients about this, I would say, “Look, it’s an option to go without radiation. You have to realize if you do that, there is a higher chance of the cancer coming back in that same breast.” And I think that this doesn’t really change practice too much at this point because I think doctors were already having this conversation with their patients based on some older studies. But it is nice to have this extra reassurance that, if, as a physician, you see a woman who's over 65, maybe she’s not in great health, maybe she has a lot of other medical problems, you're worried about giving her radiation, that if she does have one of these small, low-risk tumors, that foregoing the radiation is a legitimate option.

Jamie DePolo: Okay, and I did want to bring up too, I can’t remember if we mentioned this, but all the women in this study, also, the cancers were hormone-receptor-positive, so they were getting hormonal therapy whether or not they got radiation therapy. And I remember hearing one of the researchers saying that he really felt that was more effective at reducing recurrence than the radiation. Now, that was just his opinion, but he was the one that did the study.

Dr. Brian Wojciechowski: Now you make a really good point, and hormone therapy targets the whole body, whereas radiation only targets the breast. And if I’m going to spare a woman the radiation, I want to make sure that she’s fully committed to the hormone therapy. So, if she’s not tolerating it well, if she develops problems on the hormone therapy, then we’re sort of taking that back-up option off the table if she can’t finish it. And then we’re going to be worried that, well, she didn’t get radiation, she didn’t get hormone therapy, and the risk of the cancer coming back will be higher. So if you’re going to skip the radiation, the bottom line is you need to have a woman who’s committed to the hormone therapy.

Jamie DePolo: Okay, and one other thing I thought was interesting, the women in the study, the four women who did have a recurrence (I don’t know if it was four, but that was the percentage), because they didn’t have radiation, it was interesting to me that they then had the option of having another lumpectomy. They didn’t have to have a mastectomy right away. They could have another lumpectomy and then have the radiation. So I thought that was interesting, too, because that was another sort of less invasive option that was available to them if they wanted to do that.

Dr. Brian Wojciechowski: Yeah, because if you have radiation in the breast and the cancer recurs in that same breast, it’s very hard to go back and do radiation and spare the breast. So, usually women who've had radiation have to get a mastectomy later on if the cancer comes back in that breast. If the woman skips the radiation, then the cancer coming back in that same breast, she has the option of having the radiation in the future should she have a recurrence.

Jamie DePolo: Okay. All right. Now, one very hot topic at the San Antonio Breast Cancer Symposium today was mammograms. And the first speaker of the day was Gilbert Welch, who some people may know, he had sort of a point/counter-point with our president and founder Dr. Marisa Weiss in the Wall Street Journal, where they talked about the benefits and the risks of mammograms. And he spoke this morning, and then another researcher spoke a little bit later in the morning, about the supposed disparities in the numbers of mammograms. And, you know, we’ve heard a lot about this in the last few years with the Task Force recommendations coming out and then all the publicity about that, and then most organizations not following them, the proposed changes weren’t adopted. I know at Breastcancer.org, we believe women, starting at 40, should get regular mammograms. What’s kind of the take away from all this? I mean, I understand that false positives, which if you can explain what those are, why those are upsetting, but it seems to me that having a cancer and not knowing about it would be more upsetting.

Dr. Brian Wojciechowski: Yeah. You know, mammograms are not perfect, and no test is. The ideal test would have no down sides, no side effects, no false positives, no false negatives that would lead to no unnecessary treatments and cause women no excess anxiety. Now, we’re never going to achieve that, so we’re kind of stuck with what we have. I think the problem with mammograms that people are starting to highlight now is that there are a certain number of false positives.

Jamie DePolo: And if you could explain what those are.

Dr. Brian Wojciechowski: A false positive is when a test comes back positive, suggesting that the patient could have cancer, but in the end, when a biopsy is performed, there is no cancer. And people are concerned about mammograms causing a lot of false positives. So, something like 10% of women who get mammograms will have to go back for further imaging. Some of those women will have to have biopsies, and many of them will not have cancer, and this is going to result in a lot of anxiety and excess procedures.

Now, let me clarify some misinformation about mammograms that’s circulating right now. In the past few years, a chorus of voices in the media, in newspapers, on TV, authors, journalists, even prominent physicians and cancer survivors, have begun to say things like, "Mammograms don’t do any good at all or even that they do harm." This is very surprising to me because it directly conflicts with the data.

The best kind of scientific study that you can do is a prospective randomized trial. That’s where you start with two groups, and one group gets mammograms and one group doesn’t. And all the best studies have shown consistently that women who get mammograms, their lives will be saved if they get the mammograms as opposed to if they just wait until they can feel the tumor themselves or it becomes symptomatic. Now, I think women deserve to know that you have to screen a lot of women in order to save one life. So, for example, from age 40 to 50, about 1,900 women have to be screened, and one of their lives will be saved. Now you get more bang for your buck as you get older. That number goes down to about 1,000 between age 50 and 60, where you screen 1,000 women and you save one life. And above age 60, you only have to screen about 300 women to save one life.

So, not all of the women who are diagnosed with breast cancer will have their life saved by screening. The question is, why is that? Well, even if we catch it at a later stage, we’re still curing most women with breast cancer. So it’s more a function of our treatments are that good than it’s a function of the failure of mammograms. Okay?

Jamie DePolo: Okay. That makes sense, because we do have so many more treatments available right now. And people at the session this morning also made an interesting point, that, well, it makes sense because screening mammograms, while, as you said they’re not perfect, they have improved. So we now have digital mammograms, we now have digital tomosynthesis, which is basically a 3D image of the breast rather than a 2-dimensional image, which is what a mammogram is, and you can find a lot more things. So it’s true, we are seeing more cases of ductal carcinoma in situ (DCIS) diagnosed, but we have better techniques. I mean, it’s kind of like with any of the cancers, as the detection tests get better, we find more of it. So does that mean there’s actually more cancer or does it just mean we’re better at finding it? I don’t know.

Dr. Brian Wojciechowski: Yeah. Well, these new technologies are going to allow us to find the cancers that we’re not finding with standard mammograms now. There’s going to be less callbacks, too, so a lower rate of false positives. We have to take that into account. But here’s the bombshell, Jamie. To the woman listening to this podcast, I would ask the question, "Does finding the cancer earlier mean anything to you, even if there’s only a small chance that it would save your life? Or even if it means you might live just as long had you simply found the cancer on your own, but got to keep your breast, for example, or avoid chemotherapy?" So, a life saved is not the end of the story. Early detection leads to less invasive treatments, less chemotherapy, more women keeping their breasts. So if the answer to any of those questions is yes, then anyone on the other side of this debate needs to rethink their entire position.

Jamie DePolo: Very good. I agree, and as I said earlier, Breastcancer.org wholeheartedly supports regular screening mammograms for every woman age 40 and over. If you know you’re at high risk or you have a family history, then you need to talk to your doctor about a more tailored, perhaps more frequent, screening plan. So, we wholeheartedly support it, and that’s our story on mammograms.

Now, there were a couple other studies that were very intriguing, very exciting, but don’t necessarily have any immediate applications. But we thought we would mention it to let folks know what’s coming down the pike, what's looking out in the future as far as treating breast cancer, looking at the different types of breast cancers. And obviously we’re not going to see any of these things for maybe 5 to 10 years, but we just wanted to let you know that these are things that are being talked about and that the scientists are very excited about. So, what did you pick out for us, Brian?

Dr. Brian Wojciechowski: So, I think one of the most exciting things that I saw today were a few studies highlighting tumor infiltrating lymphocytes.

Jamie DePolo: Okay, now you have to explain to us what those are.

Dr. Brian Wojciechowski: Yeah. In plain English, basically those are white blood cells that infiltrate into the tumor. Your white blood cells are basically your immune system, so these are the cells that circulate through your body and fight things like infection or foreign invaders. When you see these cells in a tumor, according to the studies that we saw today, that’s a good thing. That’s a good prognosis.

Jamie DePolo: That is good. Okay.

Dr. Brian Wojciechowski: Yeah. Women who have these tumor infiltrating cells respond better to treatments and have a higher rate of cure. So, the reason this is so exciting is that the new drugs that are coming out today that really have us excited are drugs that target these immune system pathways. You may have heard about drugs that target PD-1 or PD-L1 or CTLA-4.

Jamie DePolo: Are those genes or pathways or what…

Dr. Brian Wojciechowski: So these are receptors on cells in you body, and when you target these receptors, that enhances your immune system, it enhances your immune system’s response to the cancer. It helps your own white cells fight the cancer. And in some other diseases like melanoma and lung cancer right now, we are seeing dramatic responses in the metastatic, the stage 4 setting, where tumors are shrinking to degrees that we never saw in the past.

Jamie DePolo: Oh, wow.

Dr. Brian Wojciechowski: So, basically, the drugs that we’re really excited about now, based on the studies that I saw today, those drugs may show some promise in breast cancer but that’s certainly a couple years down the line.

Jamie DePolo: Okay, and it was interesting to me, too, because nobody before, at least I’ve not heard, has not really talked about breast cancer being involved with the immune system. So I thought that was very interesting, and, as you just said, opens up kind of this whole new way to treat it, if you can get the immune system working on treating the breast cancer as well as any of the other treatments that we’re currently using.

Dr. Brian Wojciechowski: Yeah. Cancer cells have a lot of different mechanisms whereby they are allowed to grow and proliferate and spread in the body, and one of those weapons that the cancer cell uses is called immune escape. So they figure out ways to avoid your own immune system fighting the cancer. Truthfully, we all probably have cancer cells in our body from time to time that develop and divide and then get picked off by our immune system.

Jamie DePolo: Oh, so the immune system just takes care of it.

Dr. Brian Wojciechowski: Yeah, and you never see it.

Jamie DePolo: You never know.

Dr. Brian Wojciechowski: But sometimes those cancer cells develop the ability to avoid the immune system, and that’s where you run into a real problem. So we’re learning now to target those pathways and enhance the body’s own immune response.

Jamie DePolo: Okay. Okay, that sounds very fascinating. Was there another study you wanted to talk about in the future or was that the only one? I can’t remember now.

Dr. Brian Wojciechowski: So, someone else talked about tumor stem cells, which are also a long way off, but these are the very immature, very early-stage cells in the tumor that basically can reproduce themselves and reproduce the whole cancer. And we think they may have something to do with tumor recurrence after the initial treatment, that these cells may lay dormant in bone or other parts of the body and eventually can be triggered to reproduce and cause a cancer recurrence. There are some companies now that are going to develop therapies to target these stem cells. You know, that’s very exciting as well, although it’s not quite ready for primetime. It’s something I’m going to be looking at closely in the next few years.

Jamie DePolo: Okay. Yeah, and we should reiterate that these two studies we’re talking about, it’s not something you can ask your doctor about now, there’s nothing available, but researchers are talking about it, they’re working on it, and we hope within the next 5 or 10 years, maybe, there would be something available.

Dr. Brian Wojciechowski: Oh, sure. There’s a lot that’s coming right around the corner.

Jamie DePolo: That’s great. Well, we want to thank everybody for listening, and we hope you enjoyed it. This is our inaugural podcast; we’re down here in San Antonio at the San Antonio Breast Cancer Symposium. I’m Jamie DePolo, the Breastcancer.org senior editor. I’m with Brian Wojciechowski, who is our medical advisor, our excellent medical advisor, who broke down all these studies for us, and we will be back again tomorrow with more research news about breast cancer. So thanks everybody for listening.

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