You are here: Home: BCU 2 | 2006: Harold J Burstein, MD, PhD

Tracks 1-7
Track 1 Introduction
Track 2 Clinical implications of adjuvant trastuzumab trial results
Track 3 Management of low-risk HER2-positive disease
Track 4 Adjuvant trastuzumab monotherapy
Track 5 Delayed adjuvant trastuzumab
Track 6 Duration of therapy with adjuvant trastuzumab
Track 7 Selection of adjuvant hormonal therapy for patients with ER-positive, HER2-positive disease

Select Excerpts from the Breast Cancer Update Meet The Professors Session, held at the 28th Annual San Antonio Breast Cancer Symposium, December 8-11, 2005

Track 2-3

DR LOVE: Would you summarize the results of the adjuvant trastuzumab trials?

DR BURSTEIN: Within a span of eight months, the results from a number of randomized clinical trials, all with a fundamental design of chemotherapy with or without trastuzumab, were reported.

This experience cumulatively totals more than 10,000 patients: 3,200 in the BCIRG trial, roughly 3,000 from the pooled NSABP and Intergroup analysis, approximately 3,500 from two arms of the HERA trial, and a couple of hundred from the FinHer study (Slamon 2005; Romond 2005; HERA Study Team 2005; Joensuu 2005).

I’m sure that at some point, someone will do a meta-analysis, but I don’t believe it’s necessary because the hazard ratio for risk reduction when trastuzumab is added in the adjuvant treatment of HER2-positive disease has been remarkably consistent — approximately 50 percent. When you consider the scale of this research enterprise and the sample size, that’s really quite astonishing.

It’s also impressive that the absolute benefit has been incredibly consistent.

In all of these trials, the patients who received chemotherapy alone had approximately a 30 percent risk of recurrence, whereas the patients who received chemotherapy with trastuzumab had a 15 percent risk.

DR LOVE: Can you comment on the data from the BCIRG 006 adjuvant trial that compared AC followed by docetaxel versus AC followed by docetaxel plus trastuzumab versus docetaxel, carboplatin and trastuzumab?

DR BURSTEIN: The seminal question for that trial was how the triplet — docetaxel, carboplatin and trastuzumab (TCH) — would compare with AC followed by docetaxel/trastuzumab and whether we could avoid using an anthracycline.

Although the numbers were not statistically significant, it struck me that there is still an advantage for the anthracycline-based chemotherapy. The tradeoff that Dr Slamon reported is that there seems to be a slightly greater risk of cardiac toxicity for the women who received the anthracycline-based regimen, but only about a one percent difference in terms of clinical cardiotoxicity events.

I think the TCH regimen is provocative, and we should continue to watch the data as they mature. However, for the moment I will continue to use AC followed by taxane with trastuzumab as my principal adjuvant regimen for HER2-positive disease.

DR LOVE: What are your thoughts about the TOPO II data that Dr Slamon introduced?

DR BURSTEIN: TOPO II is a gene locus that’s on the same chromosome as the HER2 gene locus, and when there is amplification of HER2, sometimes those amplicons, that stretch of DNA that gets amplified, include the TOPO II gene. Dr Slamon showed that the patients whose tumors are particularly enriched for TOPO II seem to selectively benefit from the anthracycline-based chemotherapy.

I think that is a provocative finding, and it fits with a good deal of preclinical and clinical literature. However, for the moment, it is not a commercially available test nor, frankly, one that is commercially necessary, because I think most patients should still get the anthracycline-based, trastuzumab-based regimen.

DR LOVE: How do you manage a HER2-positive tumor smaller than one centimeter in the adjuvant setting?

DR BURSTEIN: The honest answer is that we don’t know whether these women need trastuzumab. We do need to be respectful of the fact that these women have a better prognosis because their tumors are so small. Certainly for women whose tumors are ER-positive and less than one centimeter, I’ve not offered trastuzumab.

For patients with ER-negative disease, I suppose one could consider trastuzumab, though the quantifiable gains from adding this agent are not known. It would be interesting to conduct a study evaluating trastuzumab with or without chemotherapy in patients with very small tumors. Maybe we can begin to eliminate chemotherapy for the lower-risk patient population if we can alter the natural history of their disease.

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