You are here: Home: BCU 2 | 2006: Peter M Ravdin, MD, PhD

Tracks 1-7
Track 1 Introduction
Track 2 Use of biomarkers to select adjuvant hormonal therapy
Track 3 Sequencing adjuvant tamoxifen and anastrozole: Five-year analysis of ABCSG-8
Track 4 Benefit of delayed therapy with letrozole observed in MA17
Track 5 Up-front hormonal therapy in pre- and perimenopausal patients
Track 6 Duration of hormonal therapy
Track 7 Potential benefit of identifying patients with de novo tamoxifen resistance

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

DR LOVE: Can you review data presented here on biomarkers to identify subgroups of patients who would benefit from a specific endocrine therapy?

DR RAVDIN: The ATAC trial found that the extra advantage of an aromatase inhibitor — in this case, anastrozole — was seen strongly only in the patients with ER-positive, PR-negative disease (Dowsett 2005). This finding was based on 6,000 patients, and it had a very large p-value.

However, the BIG FEMTA study, which compared letrozole to tamoxifen as up-front therapy, did not find a significant difference in the efficacy of these agents relative to the status of the progesterone receptor (BIG 1-98 Collaborative Group 2005). The BIG investigators also evaluated the HER2 status of roughly 4,000 patients because data suggest that aromatase inhibitors may be more effective in tumors that are HER2-positive and ER-positive. They conducted a well-controlled study and found no significant difference on the basis of HER2, either.

The relationship between hormone receptor status and the impact of endocrine therapy was also examined in the NCIC-CTG MA17 trial. This trial randomly assigned patients who had taken five years of adjuvant tamoxifen to five years of letrozole versus a placebo. Patients with ER- and PR-positive disease particularly benefited from letrozole (Goss 2005).

However, patients with ER-positive but PR-negative disease received no additional benefit from letrozole compared to tamoxifen. Interestingly enough, that observation is exactly opposite to the ATAC observation.

At this point, we have no way in clinical practice to specifically select patients, and in this state of uncertainty, an aromatase inhibitor is probably the better adjuvant endocrine therapy for postmenopausal patients with ER-positive breast cancer.

DR LOVE: An updated analysis was presented on the MA17 trial, which examined patients who had originally received a placebo and then switched to letrozole after the unblinding. Could you comment on that data?

DR RAVDIN: Paul Goss presented follow-up data on patients who participated in the Canadian trial comparing letrozole versus a placebo after completing five years of adjuvant tamoxifen. When they broke the code at two and a half years, some of the placebo patients decided to switch to letrozole and a few chose no further therapy. The patients who went on to take letrozole had much lower recurrence rates, even though some of them had been off any endocrine therapy for four years.

This analysis suggests that even years after stopping tamoxifen, patients can gain benefit from an aromatase inhibitor. In my practice, that means some of my patients, particularly the patients at high risk who have already been off tamoxifen for a year, should consider taking an aromatase inhibitor, specifically letrozole, because it’s the only one that has been tested in this context.

DR LOVE: A rerandomization of all the patients who completed letrozole on MA17 is underway to compare another five years of letrozole to no further therapy. What do you think this will show?

DR RAVDIN: Aromatase inhibition probably should be continued indefinitely, and my opinion is based on two factors. One is that if a patient stops an aromatase inhibitor, her hormone levels will, of course, recover. Second, it may be more difficult to develop resistance to estrogen deprivation than it is to develop resistance to tamoxifen. Tamoxifen is an agonist/antagonist, and preclinical work has shown that it can be reinterpreted as an estrogen by cancer cells, but I can’t conceive of a pathway that would reinterpret no estrogen as an estrogen.

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