Aromatase Inhibitors and Prevention of Breast Cancer

The above rationale and positive results with SERMs underpin the case for trials of aromatase inhibitors in the preventative setting. However, the potent endocrine effects ofthird generation inhibitors make long-term monitoring of bone and lipid profiles mandatory. Ongoing adjuvant trials with aromatase inhibitors provide information on the incidence ofnew contralateral BCs and side-effect profiles. The large ATAC trial shows a significant reduction in contralateral cancer in the aromatase inhibitor (anastrozole) group compared with tamoxifen (35 vs 20, p =

0.007. compared with an expected 85 cases with no treatment,) (79). Aromatase inhibitors also have not been successful in premenopausal women (80-82) because of the high levels of aromatase activity in the premenopausal ovary and compensatory feedback loops (13). However, the new aromatase inhibitors may be sufficiently powerful to produce effective blockade, but they are not yet used routinely in premenopausal women

Pilot chemoprevention studies which target high risk women, using third generation aromatase inhibitors are being planned or underway. One study has identified a small cohort of women with either DCIS or benign breast disease who were treated for 3 months with letrozole, the primary objective being to measure surrogate biomarkers of BC risk, and bone and lipid metabolism (83). The WISE trial aims to recruit women at risk on account of high circulating Es and randomize to either letrozole (1 year) or placebo. The National Institute of Canada is conducting double blind, multicentrer trials to evaluate the effect of letrozole, exemestane, or placebo on postmenopausal women with high breast density (84).

There are plans for two large Phase III trials. One will compare anastrozole with placebo in 6,000 postmenopausal women (IBIS II), the other will randomize 5,100 women to receive either exemestane or placebo or exemestane plus a COX-II inhibitor (NCIC CTL MAP3).

From PMS To PPD

From PMS To PPD

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