Important Advances in the Treatment of Breast Cancer

Clifford Hudis, MD

Today we discuss the latest results from the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium, held September 13–15 in San Francisco, with Dr. Clifford Hudis, a breast cancer oncologist who is chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York and a professor of medicine at Weill Cornell Medical College.

Dr. Hudis is also the ASCO president-elect for the upcoming year and is involved in both clinical and translational research to develop better chemotherapies, hormone therapies, and targeted agents.

-Interviewed by Anna Azvolinsky, PhD

CancerNetwork: Dr. Hudis, what in your opinion is one of the most exciting recent advances for treating breast cancer?

Dr. Hudis: I don't think it is possible to say that there is only one exciting, recent advance. The treatment of breast cancer, of course, is multidisciplinary and there are important advances in most of the areas of practice. Some of the key recent advances that I think are really important are one, the general trend toward less surgery for breast cancer. We see, for example the use of sentinel node instead of actual dissection that has now evolved with the recent ACOSOG study [Trial Z0011] to indicate that we can skip axillary dissection even in the setting of a positive lymph node in appropriate patients. Maybe in the future we will get away from really looking at lymph nodes at all. So that is one example.

I think the second one is the explosion in the use and development of anti-HER2 agents with really practical clinical importance. For the medical oncologists treating advanced HER2-positive breast cancer there are now a number of drugs with a high degree of reproducible, reliable activity in this disease, and developing new drugs in that crowded field and figuring out the optimal sequence and utilization of those drugs remains a critical challenge, but it's exciting to have so many agents that really can contribute to improved outcomes.

The third and final point I would make is overall, what we are now seeing is the beginning of a new era where our increasing understanding of the molecular biology of breast cancer is finally translating into meaningful clinical advances in treatment. And a concrete example, a recent one, is the development of the mTOR inhibitor, everolimus (Afinitor), in breast cancer. It isn't only that it is active which is obviously good enough, but it is that it reflects years of painstaking work identifying the fact that the PI3Kinase pathway is so frequently activated in estrogen receptor (ER)-positive breast cancer. So the use of this drug was very specific and targeted to a population of patients where it was most likely going to be effective. And I am optimistic that we are going to see more and more of that.

CancerNetwork: So just focusing on everolimus, the BOLERO-2 updated 18-month results were presented at this Breast Cancer Symposium and everolimus is also being developed for other breast cancer populations. How do you see this drug specifically in the treatment paradigm for both hormone-positive and other types of breast cancers?

Dr. Hudis: Well, the two areas where I obviously think the development is going forward is the hormone-receptor positive as well as the HER2-positive. In the former situation where we have more actionable, clinical data at the moment. The BOLERO-2 data, of course, has held up nicely. It is very clear that in a relatively hormone-refractory patient population, the addition of the mTOR inhibitor prolongs progression-free survival and offers, therefore, an ability to delay the use of chemotherapy for these patients. And that represents a potential advance in terms of quality of life, if nothing else.

Now, having said that, it is important to point out that everolimus is not hormone therapy. It has substantial toxicities in comparison to hormone therapy that will require a little more attention on the part of the medical oncologist. Whether it is the pneumonitis or stomatitis or the change in taste that many patients perceive, this is not a "set it and forget it" type of drug the way many hormone therapies are. And so, you ask how I see it, I see it as an option to sequential hormone therapy for ER-positive breast cancer but it is not, again, one to be casual about.

CancerNetwork: Going back to what you mentioned about the frequency of surgery that we are seeing now and in the future, is there an estimation of how many patients are spared from surgery and what that number can go up to in the future?

Dr. Hudis: I think because there is evolution right now these numbers are going to be changing. But let's just say right now that the simple majority of patients in the United States have node-negative disease and for them the development of the sentinel node as a first pass was critically important since most of those patients now can be treated without a full axillary dissection and its consequences. In terms of the ACOSOG study, that obviously applies to a smaller cohort of patients who have a low number of positive lymph nodes. But again, I think each little bit helps, and I think that the broader question for our community is going to be whether any nodal status staging is really required in the distant future.

CancerNetwork: In terms of all of the massive tumor sequencing efforts that are ongoing, to identify new driver mutations and potential biomarkers, do you think that this nonbiased and partly biased approach will result in new innovations for breast cancer patients in the short or mid-term?

Dr. Hudis: Well, I am sure it is going to result in innovations, but to be fair, the very approach really steps us out of the arena of breast cancer–specific medicine, when you really get right down to it, because it is the same approach that is being undertaken in a variety of different tumors. And it is identifying, when it works, so-called actionable mutations, meaning mutations or abnormalities for which there are targetable drug. But the important step isn't that there is a target and a drug, the important step is that drugging that target actually makes a difference. And frankly, this so-called precision medicine is going to require a new kind of paradigm for drug approval and development because it is possible that we are going to see very many numbers of niches of breast cancer and other solid tumors where the numbers of patients are so modest that conventional phase III trials will be strained. So I am very optimistic about this finding, a new approach to disease, but I am a little more cautious about how we are really going to generalize this to the public.

CancerNetwork: One of the hurdles you were saying, part of that is the identification of different types of triple-negative cancer, which remains difficult to treat because it is really a cluster of different types of breast cancers, both biologically and molecularly. Do you think we are close to teasing out actual subtypes of triple-negative breast cancer?

Dr. Hudis: Well, triple-negative breast cancer is tough to treat because on average, it has a poor prognosis, and the only known effective therapy is cytotoxic chemotherapy whereas for the HER2 and the ER's, of course, we have less toxic and targeted treatments. That said, we are beginning to pull apart triple-negative breast cancer into a few recognizable subtypes, and what my group just presented earlier this year, a first report of an androgen-receptor agent, called bicalutamide, for the small subset of triple negatives that actually overexpress the androgen receptor (AR). And there has been another group from Vanderbilt that has identified a similar group of AR-positive tumors using a tissue and microarray approach. And so I think that we are beginning to make some progress, and in the case of AR, for example, we are able to offer now, a relatively nontoxic old drug, albeit one that is not approved for use in women but nonetheless is nontoxic (or relatively nontoxic in lieu of chemo). And I think it is an open question as to how many identifiable subtypes of triple-negative breast cancer we will find for whom we can offer less toxic therapy.

CancerNetwork: Finally, are there any presentations or results at the ASCO Breast Cancer Symposium that you would like to highlight that stand out in terms of results?

Dr. Hudis: Well, in fairness, you know the ASCO Breast is a slightly different kind of meeting. This is a high-level, interactive multidisciplinary meeting where many of the luminaries in the field are brought together with really interested, and I think, intellectually curious clinicians for discussions. And so, this is not a meeting where there will be late-breaking, cutting edge, never-before-presented research. And so I wouldn't look to ASCO Breast for that. It's function is really, I think, better described as allowing clinicians who tend to be educated with regard to the best evidence and to, therefore, practice the best quality breast cancer treatment.

CancerNetwork: OK, great. Thank you so much for joining us, Dr. Hudis, we really appreciate it!

Dr. Hudis: My pleasure, thank you for having me.