Based on the MAP.3 findings, should we be using exemestane to prevent breast cancer in high-risk patients?

Dr. Harold Burstein: The risk of developing breast cancer was 2.5% in the placebo arm, vs 1% to 1.5% risk with exemestane. Also, the cancers that were avoided were probably ones with good prognosis. You have to ask, therefore, “How important is this therapy?” While exemestane was reasonably well tolerated in the study, there are real side effects. Osteoporosis was not increased, but with only 3 years of follow-up the late effects may not be obvious. Many cancer drugs have side effects that all but the most motivated patients will balk at, so will women who don’t even have cancer take them?

We have proven the concept of prevention of breast cancer. The question is, “Have we shown it in a way that is compelling to real people in the real world?” I am not sure we have, but for patients who are interested, we clearly have well-documented options.

Dr. Daniel F. Hayes: I agree. Exemestane does not look any more protective than the other aromatase inhibitors, and recent data suggest there may be a slight excess of cardiovascular events with these agents, vs tamoxifen, over 10 years or so. In terms of using these drugs in the prevention setting, where the benefit is very small and no reduction in mortality has been seen so far, we must be thoughtful about their widespread adoption.

Based on the MAP.3 data, can I use an aromatase inhibitor instead of tamoxifen in the postmenopausal ductal carcinoma in situ (DCIS) patient after surgery, especially if she has cardiovascular risk factors and I am worried about thromboembolism?

Dr. Carey K. Anders: In the absence of data, I would not recommend an aromatase inhibitor. Your rationale makes sense, but I would not leap from a preventive strategy to treatment of preinvasive disease.

Dr. Burstein: In every setting, from prevention to in situ cancer to early-stage cancer to metastatic disease, tamoxifen and the aromatase inhibitors have had almost identical activity. The one gap is DCIS. If I thought my patient needed one of these drugs and could not take tamoxifen, I would not quibble about using an aromatase inhibitor, but because of the data void, I would generally prefer tamoxifen.

Dr. Hayes: I would argue that tamoxifen is probably safer in the average patient. I am concerned about the long-term risk of osteoporosis and heart disease. The patient with DCIS has less than a 5% chance of distant recurrence or death. I would not use an aromatase inhibitor unless she cannot take tamoxifen and is at very high risk of breast cancer.

What study from this year’s ASCO Annual Meeting do you consider most practice-changing?

Dr. Anders: I would say the Whelan study of regional nodal irradiation was the most practice-changing.¹ Our radiation oncologists have actually been doing regional nodal irradiation, based on postmastectomy findings, but these data reinforce that practice. For patients with one to three positive nodes or tumors > 3 cm, you should consider regional nodal irradiation.

Dr. Burstein: We have undersold the value of regional radiotherapy for a long time, although data from postmastectomy patients have shown its value. I find the Whelan data very compelling.

Dr. Hayes: I agree. Clinicians should discuss this paper with their radiation oncologists.

Studies are now showing improved outcomes with combined HER2 blockade. How do you give trastuzumab and lapatinib together in clinical practice?

Dr. Burstein: Three trials have shown that combining trastuzumab and lapatinib improves pathologic complete response (CR) rates, and a fourth study is ongoing. Personally, I think the question has been answered. But does any of this matter in terms of improving long-term outcome? For this, we await the results of ALLTO, which is evaluating the combination in the adjuvant setting with adequate numbers of patients followed long-term.

If ALLTO shows a win for the combination, lapatinib will be incorporated into standard adjuvant treatment and therefore will be part of neoadjuvant regimens as well. Secondly, it will validate, at least in HER2-positive patients, that achieving pathologic CRs will lead to long-term improvements in outcomes. At this point, outside of a clinical trial, however, trastuzumab-based treatment remains the standard, and I am not giving combination anti-HER2 therapy. ■

Reference

1. Whelan TJ, Olivotto I, Ackerman I, et al: NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer. 2011 ASCO Annual Meeting. Abstract LBA1003. Presented June 6, 2011.