Breast Cancer Update .com - Web Guide 2

Tracks 1-7

Track 1	Introduction
Track 2	Meta-analysis demonstrating a survival advantage in switching from tamoxifen to anastrozole
Track 3	Increased incidence of gynecological events with tamoxifen in ATAC
Track 4	Use of mathematical modeling to determine optimal up-front hormonal therapy

Track 5	Initiating therapy after five years of anastrozole
Track 6	Incidence of fractures and bone loss associated with aromatase inhibitors
Track 7	Time course for developing endometrial cancer with tamoxifen

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

Track 2-3

DR LOVE: A number of adjuvant endocrine therapy trials were presented at the San Antonio Breast Cancer Symposium (2005). Can you summarize what those trials demonstrated?

DR HOWELL: The data from these trials created another epoch-making moment for aromatase inhibitors. To begin with, the data from Jakesz are important because they show that the effect of switching is not quite as big as we once thought. While the hazard ratio is approximately a 40 percent reduction in the switching studies, when they took into account the first two years, the reduction in the hazard ratio was about 24 percent ( Jakesz 2005b).

Another significant finding was the survival advantage seen in the meta-analysis of the ARNO 95, ABCSG-8 and the ITA trials. It was an important analysis because it showed, for the first time in an unselected population, the survival advantage of switching to anastrozole. Based on that, I feel we should use anastrozole in that clinical setting ( Jonat 2005).

Paul Goss and Jim Ingle’s papers also presented some beautiful data — although some of that is selected — demonstrating the efficacy of letrozole for patients with hormone receptor-positive breast cancer (Goss 2005b, Ingle 2005).

Combined, I believe these data highlight the importance of the aromatase inhibitors therapeutically, and we’ve also seen that apart from the bone events and aching joints, aromatase inhibitors are better than tamoxifen as far as toxicity is concerned.

DR LOVE: Can you comment on the gynecologic events data from the ATAC trial?

DR HOWELL: The ATAC trial, because of its long follow-up, is providing us with some good gynecological data (Duffy 2005). Basically, it shows that gynecological events occur much more often with tamoxifen.

What really impresses me is the data showing that women are undergoing many more investigations — hysteroscopies, dilatation and curettages, biopsies — and more hysterectomies on tamoxifen. The hysterectomy rate on the tamoxifen arm is 5.1 percent versus 1.3 percent among the patients taking anastrozole.

Track 6-7

DR LOVE: Can you discuss the issue of bone loss with aromatase inhibitors?

DR HOWELL: All three aromatase inhibitors are showing about two to three percent bone loss per year, and we need to do something about that.

What’s interesting to us is that in the ATAC data, while the fracture rate was increased with anastrozole, it leveled off, and when the patient stopped treatment, the curves came right back together. If that’s true, that’s fantastic, but we need more data to confirm that.

I asked our bone specialists whether bone density can improve that quickly, and they pointed out that when steroids are stopped, bone reforms very rapidly, and they were not surprised by our findings.

DR LOVE: Would you comment on Delozier’s data evaluating side effects and the duration of adjuvant tamoxifen?

DR HOWELL: Delozier et al showed there was no difference in the rate of endometrial cancer among patients who had taken two to three years of tamoxifen versus 13 years, which is very surprising (Delozier 2005). They’re a good research group, so I suspect their finding is right. This suggests that the maximum induction might be in the first two to three years of therapy.

We found in the ATAC data that there is a bigger difference between tamoxifen and anastrozole in the first two and a half years than in the second two and a half years of treatment, which supports Delozier’s finding, but obviously we need more data to see exactly what’s happening.

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