In this Breastcancer.org podcast, Brian Wojciechowski, M.D., Breastcancer.org’s medical adviser, talks about four studies that were presented at the 2015 San Antonio Breast Cancer Symposium, December 8-12, including studies that offer encouraging news about treatment for women diagnosed with triple-negative disease and metastatic, HER2-positive breast cancer. Listen to the podcast to hear Dr. Wojciechowski explain:
- what luminal A breast cancer is and why women diagnosed with this subtype didn’t seem to benefit from chemotherapy after surgery
- why adding carboplatin to a standard chemotherapy before surgery for triple-negative breast cancer improved pathologic complete response rates and what this means for women with triple-negative disease
- why postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer who are taking an aromatase inhibitor and have experienced bone loss might want to consider taking the targeted therapy denosumab
- results showing that Kadcyla improves overall survival in women diagnosed with metastatic, HER2-positive breast cancer that has stopped responding to Herceptin and Tykerb
Running time: 18:51
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This podcast was made possible by the generous support of Lilly Oncology.
Jamie DePolo: Hello, everyone, I'm Jamie DePolo, the senior editor of Breastcancer.org. This podcast, we're going to talk about some of the studies that were presented at the 2015 San Antonio Breast Cancer Symposium. My guest today is Breastcancer.org's medical adviser, Dr. Brian Wojciechowski, and we’re going to talk about four studies.
The first one looked at how women with a certain type of breast cancer, luminal A breast cancer, did not benefit from chemotherapy. And Dr. Brian, if you could explain to us, what is luminal A breast cancer?
Dr. Brian Wojciechowski: Well, Jamie, there are different ways of characterizing breast cancer in terms of the relative risks. So you can look at, say, tumor size and node status. You can look at subtypes such as ductal, lobular, tubular, that sort of thing. But more and more these days, we’re looking at the biology of tumors, specifically what genes do the tumors express. And one way of looking at that is looking at something that we call the intrinsic subtypes. And there are four basic subtypes. They go by the names luminal A, luminal B, HER2-enriched, and basal-like, which is triple-negative.
So luminal A is the most common subtype and the type with the best prognosis, and it corresponds to tumors that are very high in estrogen and progesterone receptors. They are HER2-negative and they have a low Ki-67, which is a measure of how quickly the cancer cells are growing.
Jamie DePolo: Okay. So, essentially, we're talking about hormone-receptor-positive, HER2-negative cancers that have low levels of this Ki-67 protein.
Dr. Brian Wojciechowski: That is correct.
Jamie DePolo: Okay. So tell us a little bit about this study. The results don't seem surprising at first because you said this type of breast cancer has the best prognosis. So it doesn't seem surprising that the women who were diagnosed with it didn't really benefit from chemotherapy after surgery. But then when you kind of dig into the study, it says that these women were all premenopausal, so they were young, and their cancers were very high-risk. So what's going on in this study?
Dr. Brian Wojciechowski: This study is actually provocative because the women in this study are high-risk for recurrence with large tumors, and most of them were lymph-node-positive, meaning there was cancer in the lymph nodes. And it's provocative because what we learned from this study was that these women, even with very large, aggressive tumors, did not get any benefit from the chemotherapy that was given as part of this study.
Now, the chemotherapy they used was not what I would call modern chemotherapy. They used regimens that we don't use anymore. It's actually a very old study with 25-year follow-up. But in my practice today, for example, if I saw a woman with a large tumor that was lymph-node-positive who is premenopausal, so a younger patient, it would be very uncommon that I would not give chemotherapy in that situation. So, this study suggesting that women in this category do not benefit from chemotherapy is very provocative indeed.
Jamie DePolo: Does it matter, I know that the data was collected, I think, in the 1970s or the 1980s, so we're talking decades of time, and the Oncotype test and the other sort of genomic tests that help determine whether women would benefit from chemotherapy weren't around. Does that matter, or do you think that this study, it would add anything to it if the researchers went back and did Oncotype testing on the tumor samples?
Dr. Brian Wojciechowski: I think it's likely that they're going to go back and try to do something very similar to Oncotype testing with the tissue that they have left over. Now, generally speaking, the luminal A tumors correlate with low Oncotype tumors. So I think we're dealing with... I don't think it matters a whole lot that we don't have Oncotype data in this particular study, but if we were seeing patients like this today we probably wouldn't even do an Oncotype because they were node-positive patients with very large tumors.
Jamie DePolo: Okay. So should... I guess, what's the take-home message for women? Because it is a little confusing.
Dr. Brian Wojciechowski: Well, again, this study does not represent our current standard of care. Bear in mind that the women in this study didn't even get hormonal therapy.
Jamie DePolo: That's right, which is very strange given that the cancers were hormone-receptor-positive.
Dr. Brian Wojciechowski: Right, and I think they started this study a very long time ago. It was in Europe, so the standards of care were very different at that time. They also did not get HER2-directed therapy, like Herceptin, if they were HER2-positive, and they did not get a modern chemotherapy regimen, which we think are more effective than the chemotherapy we used to use in the past. So, based on this study, young women who are premenopausal who have large tumors or lymph-node-positive tumors should not go to their doctors and say, “Hey, I don't need chemotherapy.” They should not do that based on the results of this trial. But what I think it does tell us... it adds to the growing body of knowledge that, really, biology trumps a lot of other factors like node-positivity and tumor size. The genes that are expressed in the tumor, the receptors, the HER2 status is more important in terms of prognosis than any other factor.
Jamie DePolo: Okay. Well, that's great to know then, and hopefully more studies, and, I mean, when a woman comes to you with breast cancer, are you doing this sort of biologic testing?
Dr. Brian Wojciechowski: Yeah. It's standard practice to look at the hormone-receptor-status, the HER2-status, and the Ki-67, among other markers, so those are the factors that help me decide whether or not women will get chemotherapy. I also look at the node status, the size of the tumor, and I use the Oncotype in certain instances. And while most of the medical world is not thinking in terms of intrinsic subtypes like luminal A, luminal B, basal-like, that sort of thing, we are starting to incorporate those classifications into the way we think about breast cancer.
Jamie DePolo: Okay. Okay. Great. Thank you.
Now, the second study is actually, I think, good news for anyone who's been diagnosed with triple-negative disease, because there was a study that showed that adding carboplatin to chemotherapy actually improved overall survival.
Dr. Brian Wojciechowski: Yes. It's really nice to see some positive development in the triple-negative scene because it seems like there's been, frankly, a lack of progress for women with triple-negative breast cancer, and it's nice to see that we're starting to figure out how to better treat these patients.
Jamie DePolo: And, if you could a little bit, tell us, I think it was the GeparSixto... I have a hard time saying that name... study, and it was looking at adding carboplatin or just regular chemotherapy, right? And was it after surgery, or was it before surgery? Now I don't remember.
Dr. Brian Wojciechowski: So the GeparSixto trial is a German trial in which they gave different chemotherapy regimens before surgery. We also call that neoadjuvant treatment. Now, I would caution patients about this study as well because they used chemotherapy regimens that are not common in the United States, at least for our American patients. They used weekly chemotherapy in which they used an anthracycline, a taxane, and bevacizumab, which is also called Avastin, targeted therapy. And to that regimen they added the carboplatin. And what happened was the patients who got carboplatin had a significantly increased rate of pathologic complete response when they went to surgery.
Jamie DePolo: Okay, and you know I'm going to ask you what pathologic complete response is.
Dr. Brian Wojciechowski: Sure. Pathologic complete response is when someone has chemotherapy before surgery and they go to surgery, the breast is removed, and there's no evidence of cancer in the breast. So it's when all the cancer cells died in response to the chemotherapy. In the past few years at San Antonio, we've seen a lot of evidence that pathologic complete response predicts better outcomes in the future, better survival. And this study showed that at 3 years, disease specific survival, meaning breast cancer survival, was significantly higher in the women who achieved pathologic complete response.
Jamie DePolo: And the women who got carboplatin had a better pathologic complete response. Correct?
Dr. Brian Wojciechowski: Yes. They had a better rate of pathologic complete response, and they had a better rate of disease-free survival at 3 years.
Jamie DePolo: So how common is carboplatin? I know you cautioned people that the chemo regimens they gave in these studies weren't common in the U.S., but if a woman's been diagnosed with triple-negative and the standard regimens don't seem to be helping or... I guess, it's kind of hard because this was given before surgery. So you don't know if it's really working until you have surgery, and then if you have surgery and you don't get a PCR, or a pathologic complete response, is that bad? Does that mean your prognosis isn't as good? I mean, can you still have, you know, sort of a response to the carboplatin and have good outcomes?
Dr. Brian Wojciechowski: You don't have to have a pathologic complete response. I think women who've been treated and not had a pathologic complete response don't have to worry because, you know, she's still going to get surgery and can still definitely be cured even without a pathologic complete response.
Now, to answer the next part of your question, if the chemotherapy’s not working at all, then we would definitely consider changing completely to a different regimen that may include carboplatin.
And to answer the third part of your question, carboplatin is not a common chemotherapy in breast cancer these days except when patients are HER2-positive. If you look at the NCCN guidelines, which is kind of the bible for medical oncologists, they list every chemotherapy regimen that's commonly used, and for the non-HER2-positive population, there isn't even one regimen listed there. So it is not common to be using carboplatin in the United States. And this study doesn't really tell you, “Go ahead and start treating the triple-negative patients with carboplatin,” but I would say if a patient is listening to this podcast and is interested in potentially having carboplatin, you might speak to your doctor about seeing if there are any clinical trials available in your area.
Jamie DePolo: Okay. That's a good suggestion.
Our third study now is looking at a drug called denosumab, which is a targeted therapy, and it's commonly used to treat bone loss in women who are getting aromatase inhibitors. But now, this study found that it also improved disease-free survival for postmenopausal women who were taking an aromatase inhibitor.
Dr. Brian Wojciechowski: That is correct. And it's kind of a complicated topic here, and we'll try to unpack this as best we can. First of all, denosumab, which is also called Prolia or Xgeva, is a bone-targeted therapy. That means that it goes right to a specific protein called the RANK ligand, and what that does is it decreases the rate of what we call skeletal events, so fractures and things like that. We know that women on aromatase inhibitors benefit from this drug because aromatase inhibitors cause bone loss. And it's been very well established that if women are taking denosumab while they're on aromatase inhibitors if they've already had bone loss, that their risk of subsequent fracture will be decreased. Now, what this study is adding to that is that it seems that taking this medicine actually improves the breast cancer as well.
Jamie DePolo: And do we have an idea why that is?
Dr. Brian Wojciechowski: There's some theoretical speculation like possibly that breast cancer cells hide out in the bone microenvironment and lay dormant for a certain period of time before they would grow back and cause a recurrence, and that this drug may be affecting that microenvironment in order to... how should I say this... to suppress those cancer cells for a time. Now, this study showed improved progression-free survival, meaning there was a longer time where the women were free of breast cancer recurrence. But the author admits that the statistics were a little bit borderline, meaning there's a possibility it could all be due to chance and not the actual drug effect. So I don't expect this study to change practice behavior yet. I think we need a few more years' follow-up on it. But what I will say to women with early-stage, hormone-receptor-positive breast cancer who are postmenopausal is that they should talk to their doctor about having their bone density measured. And if the bone density is low, they should really strongly consider going on a medication like this or even a medication like a bisphosphonate, which is another class of targeted bone therapy, because it will prevent fractures and it may also help with the breast cancer itself.
Jamie DePolo: Okay. So the bottom line is we need a few more years of follow-up on this one to see whether the effect, this better disease-free survival, is due to chance or whether it actually was because of the denosumab.
Dr. Brian Wojciechowski: Yes.
Jamie DePolo: Okay. But still, if, as you said, if a woman is postmenopausal and been diagnosed with early-stage, hormone-receptor positive disease, taking an aromatase inhibitor, and is having bone loss, this is a good thing to consider because it's definitely going to improve bone density.
Dr. Brian Wojciechowski: Definitely.
Jamie DePolo: Okay. And then our last study, real quickly, is looking at metastatic disease, specifically HER2-positive, metastatic disease, that has stopped responding to Herceptin and Tykerb and also an anthracycline chemotherapy. And the medicine Kadcyla was found to actually help improve disease-free survival... or, you know, it was prolonging survival, and that's got to be a good thing. Right?
Dr. Brian Wojciechowski: Yeah. That's a pretty big deal. It's rare to actually see an overall survival benefit in the setting of metastatic disease where women have had multiple rounds of chemotherapy, so this is a pretty big deal.
Jamie DePolo: And Kadcyla is approved by the FDA, so if a woman has been diagnosed with metastatic, HER2-positive disease and it's stopped responding to Herceptin and it stopped responding to Tykerb, this would be something that she could talk to her doctor about because this is readily available and commonly used. Correct?
Dr. Brian Wojciechowski: Yeah. Well, the current FDA approval is for women with metastatic, HER2-positive disease who have progressed on Herceptin and a taxane-based chemotherapy. So it's not currently approved in the setting in which this trial was studied, but that doesn't necessarily mean we don't use it, So I would encourage women to talk to their doctors about getting this drug if they have already been treated with Herceptin and lapatinib.
Jamie DePolo: All right. Well, thank you very much, Dr. Brian. This has been very informative. Again, we were talking about four studies that were presented at the 2015 San Antonio Breast Cancer Symposium, and I thank you very much for your input.