As part of its coverage of SABCS, the cancernetwork.com spoke with C. Kent Osborne, MD, who is the director of both the Lester and Sue Smith Breast Center and the Dan L. Duncan Cancer Center at Baylor College of Medicine in Houston. He is also professor of medicine in cellular and structural biology at Baylor. Dr. Osborne sat on the executive committee for SABCS this year, and discusses not only his own research, but also the year in breast cancer and what were the most exciting advances we've seen in 2011.
—Interviewed by Anna Azvolinsky, PhD
CancerNetwork: Dr. Osborne, what, in your opinion, is one of the most exciting results that we will hear about at the meeting?
Dr. Osborne: First of all, the results of a large randomized trial known as the CLEOPATRA trial in patients with metastatic breast cancer. This trial, along with several others reported earlier this year, looks at a combination of drugs that block HER2. HER2 is a cause of the cancer in about 20% to 25% of breast cancer patients. We have made excellent progress in blocking that pathway, but still, some patients are resistant. What we're discovering based on studies presented earlier this year and those presented at the San Antonio meeting; we're going to find that a combination of drugs to more completely block the pathway is superior to the old standby, which is Herceptin [trastuzumab]—which has, itself, made a big impact in survival for breast cancer in patients with this kind of breast cancer. We're seeing a more effective regimen with the combination of other drugs that also block the pathway, and we will see the results of the CLEOPATRA study that hopefully will continue to show this result.
CancerNetwork: Can you give us a sense of how many patients become resistant to Herceptin?
Dr. Osborne: Let's look at the adjuvant setting—that is, getting chemotherapy or other hormonal therapy or Herceptin after surgery—in patients where there is no evidence of disease. These are aggressive tumors; they metastasize early and patients recur soon. Chemotherapy itself is quite effective in these tumors, and the use of chemotherapy reduced the risk of recurrence by about half in these patients.
Let's say a woman presented with a HER2-positive breast cancer and had several positive lymph nodes. That person's chance of recurrence in 10 years might be 60% to 70%, but chemotherapy lowered that by half, down to 30% or 35%. Well, the addition of trastuzumab to the chemotherapy lowered it by another half, so with trastuzumab plus chemotherapy, we have converted what is normally thought of as a more aggressive kind of breast cancer into a “relatively good” kind of breast cancer. Still, however, about half of the patients who are treated with trastuzumab develop resistance and will have a recurrence despite its use, so we're now trying to discover why that is. And we have some pretty good ideas—one of which is that HER2-targeted therapy with Herceptin only partially blocks the HER2 pathway and that more complete blockade with multiple drugs seems to be a better way of doing it.
CancerNetwork: Do you think combination therapy, across the cancers, will result in better outcomes? Do you feel that combination therapy of Herceptin added with another drug with be the standard of care for all HER2-positive patients in the future?
Dr. Osborne: Yes. But the question is: which combination? There are several that people are looking at. The CLEOPATRA study is using Herceptin combined with a drug called pertuzumab. There are other combinations reported that are very exciting, such as Herceptin combined with lapatinib, and there is a very large adjuvant trial going on now, and accrual to the trial has just been completed. It's known as the ALTTO trial and it's comparing lapatinib by itself, trastuzumab by itself, and the combination of lapatinib plus trastuzumab. When that result comes out, if I had to guess I would say that the combination of lapatinib and Herceptin plus chemotherapy will prove to be a lot better. I'm going to guess that it's also going to be better when it's used in the adjuvant setting, but that remains to be seen.
I think that when that study comes out, if it's positive, yes, lapatinib and Herceptin will become the standard, but then there's the issue of whether some of these other combinations might be just as good or better, or less toxic, and that's what people are trying to work on now.