From Bedside to Bench: A New Direction in Breast Cancer Research

Kathy D. Miller, MD; Carlos L. Arteaga, MD


January 12, 2016

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Kathy D. Miller, MD: Hi. I'm Kathy Miller, professor of medicine at the Indiana University School of Medicine in Indianapolis. Welcome to Medscape Oncology Insights, coming to you from the 2015 San Antonio Breast Cancer Symposium. Before I introduce my very special guest, I would like to talk a little bit about the history of this meeting.

The San Antonio Breast Cancer Symposium started in 1977 as a one-day regional conference. All of the fellows in the division of oncology at the University of Texas - San Antonio were recruited to present cases at the conference during lunch, and they primarily discussed hormone therapy. From those very humble beginnings, it has grown to a 5-day international conference. In 2007, the American Association for Cancer Research (AACR) began a collaboration with the San Antonio group, bringing to the table its very strong reputation for translational research.

To give us some insights on the key translational and clinical findings from studies at this year's meeting, I am pleased to welcome AACR past president Dr Carlos Arteaga. Dr Arteaga is chair of breast cancer research and is professor of medicine and cancer biology at Vanderbilt University in Nashville, Tennessee. Welcome, Carlos.

Carlos L. Arteaga, MD: How are you doing?

Dr Miller: I am doing great. Tell me: Do you remember your first San Antonio meeting? I know you aren't quite old enough to have been there in 1977.

Dr Arteaga: No, it was 1987. And I would guess that there were about 250 people, at some Marriott hotel on the Riverwalk.

Dr Miller: How have you seen the meeting grow just since AACR joined this unique partnership?

Dr Arteaga: The meeting has stayed at about the same level of attendance [an estimated 7704 attended the 2015 meeting, from 95 countries], but with the AACR we have added two awards: the AACR Distinguished Lectureship Award and the AACR Outstanding Investigator Award for an investigator under 50. We have added educational symposia and basic science symposia, and we have increased the number of travel awards for young investigators, who will be the ones carrying the torch of breast cancer research in the years to come. Remember that all of us at some point will have to exit the field, and we need new blood to come in.

The AACR handles all of the press activities of the meeting. We have also expanded the number of reviewers of the abstracts. Those things the AACR has brought to the meeting, and my general sense is that people are very happy with this partnership.

Dr Miller: It has been an incredibly successful partnership. I have to say that I have noticed a focus on translational science and better incorporation and integration of basic science in the meeting since that AACR partnership began.

Dr Arteaga: Yes, but in all honesty—because I trained with Bill McGuire and Ken Osbourne—there was always a translational flavor to this meeting. I would like to believe that the AACR has expanded and increased it, but it was translational already.

Liquid Biopsies Identify Markers of Drug Resistance

Dr Miller: Let's talk about this year's meeting. What are some of the highlights from the oral sessions and the early poster sessions?

Dr Arteaga: There are many, but let me start with those that are translational, perhaps because I am representing the AACR here with you. I can point to two reports where liquid biopsies—that is, the measurement of cancer mutations in plasma—have been able to identify cancer phenotypes or identify tumors that respond (or not) to a particular treatment.[1,2] There was a wonderful presentation yesterday by Sarat Chandarlapaty, MD,[1] from Memorial Sloan Kettering Cancer Center, in which he reported the finding of estrogen receptor (ER) mutations in a significant fraction of patients with ER-positive metastatic breast cancer that had been treated with aromatase inhibitors.

These mutations are not detected in the primary tumor or at the time of diagnosis. They occur as a function of the treatment "pressure" on that metastatic disease. The tumor that tries to evolve acquires mutations that do not depend on estrogen; therefore, they do not respond to aromatase inhibitors. And we know from the laboratory that these mutations can endow the receptor with ligand-independent transcriptional activity. They are a marker of drug resistance, anti-estrogen resistance. The nice thing is that we need not do an invasive biopsy to detect them. With this information, these patients are currently able to enroll in clinical trials with better anti-ER drugs that may act on these mutant forms of the receptor.

Dr Miller: It's an excellent example of translational research where the technology that allows us to find DNA in places where we did not expect to find it, do the sequencing, and find a mutation could not only help us understand resistance, but also point to therapies that might get around that resistance.

a big conceptual change

Dr Arteaga: Absolutely, absolutely. That is one big change we've seen. In the old days we tended to focus a lot on findings in yeast, in mice, in cell lines and then go to the bedside. One of the big changes we've seen is that now, because of the power of molecular biology, we can start from the bedside, from the clinical observation, and then go back and work those alterations at the bench—understand what they mean—and on that basis generate drugs or interventions that can then be tested at the bedside. To me, that has been a big conceptual change in the past 20 years.

Dr Miller: It's also an interesting link to history, because so much of Bill McGuire's work was done on estrogen and hormone signaling. It is almost a flashback to those days, with such a powerful study identifying these ER mutations.[1]

Should Cancer Immunologists Book Flights to SABCS 2016?

Dr Miller: There was also a big shift in talking about immune therapy, immune checkpoint inhibitors, and the role of the immune system in breast cancer. Is that something that you think we are going to see expand at this meeting? It really means bringing in a whole new group of scientists, in bringing immunologists to the fold.

Dr Arteaga: I agree that we are moving strongly into this area of immune therapy. We are learning from other tumor types, such as melanoma, renal cell carcinoma, and lung cancer, where these therapies appear to have a higher impact. I think the challenge we have in breast cancer research is to identify those tumors that are particularly sensitive to these immune checkpoint inhibitors. Yesterday we had at least four presentations[3,4,5,6,7] that looked at immune signatures, tumor-infiltrating lymphocytes, stromal signatures that may point to phenotypes, to tumor types, to subgroups that may benefit from these therapies.

There is a need, as you implied, to bring to the meeting not only immunotherapies, but cancer immunologists.

I don't think I have seen anything transformative in breast cancer with immune therapies, but I know there are many drugs out there. In the next few years we are going to learn how to use them as single therapies and in combination. For the rational development of these drugs and for the combination of these therapies with targeted therapies, I think there is a need, as you implied, to bring to the meeting not only immunotherapies, but cancer immunologists, because a lot of us in the translational field do not have that immunologic know-how that may point to new mechanisms of action and to combinations we should use. You have mentioned something that I would say is a big need in the breast cancer field.

Dr Miller: But with the strength of AACR, I think we will be able to do that pretty easily.

Dr Arteaga: I would hope so.

Patient Advocates Prove Essential Research Partners

Dr. Miller: One of the things that has always been unique and special about the San Antonio meeting, at least since the time I have been attending, has been the involvement of patients and patient advocates in the meeting as full partners. How do you see that as important in shaping our work?

Dr Arteaga: I think it's very important. I still remember the first time that I was in the study section reviewing grants for a granting agency, and next to me was a breast cancer advocate who, in fact, was a woman with metastatic breast cancer. Initially I just didn't get it. But the next day when I came to breakfast, I saw that she was talking to a lot of PhD scientists at the breakfast table, and they were all fascinated as she was telling them about her cancer history. Then I realized that this is important, to have [patients] at the table, because they help us identify the relevance of what we do. They bring a human perspective that we may be missing when we are just focusing on studies at the bench. I think it's a big thing. It's one of the big changes that we've seen in the past 20 years. When the San Antonio meeting started, that constituency was not a part of the meeting. Now it is a very strong and a very important one.

Dr Miller: They certainly are full participants and frequently have very eloquent, very pointed questions about some of the work that we do.

Dr Arteaga: We learn from them, and we should.

Dr. Miller: It's been fascinating talking with you, Carlos. Thank you so much for updating us about the meeting and this unique partnership between AACR and the San Antonio Breast Cancer Symposium.

Dr Arteaga: Thank you.

Dr Miller: I want to thank our listeners for joining us. This is Dr Kathy Miller, from the 2015 San Antonio Breast Cancer Symposium.