Breast Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Description of Evidence
Incidence of Outcomes Per 1,000 Women continued...
Aromatase inhibition or inactivation
Another class of agents, commercially available for the treatment of hormone-sensitive breast cancer, may also prevent breast cancer. These three drugs interfere with the adrenal enzyme aromatase, which is responsible for estrogen production in postmenopausal women. Anastrozole (Arimidex) and letrozole (Femara) inhibit aromatase activity, whereas exemestane (Aromasin) inactivates the enzyme. All three drugs have similar side effects, infrequently causing fatigue, arthralgia, and myalgia. Bone mineral density may be decreased, and fracture rate is increased, possibly because of the decreased bone density.
All three drugs decrease the incidence of new breast cancers in women with a history of breast cancer. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared anastrozole, tamoxifen, and the combination when used as an adjuvant HT after treatment of the primary breast cancer. Anastrozole-treated patients had a 7.1% rate of locoregional and distant recurrence versus 8.5% for those treated with tamoxifen and 9.1% for the combination. A more impressive result was the decreased rate of primary contralateral breast cancers (0.4% vs. 1.1% vs. 0.9%). Another trial analyzed the use of letrozole versus placebo in 5,187 women with breast cancer, following 5 years of treatment with adjuvant tamoxifen. After only 2.5 years of median follow-up, the study was terminated, because previously defined efficacy endpoints had been reached. Not only did letrozole-treated patients have a lower incidence of locoregional and distant cancer recurrence, they also had a lower rate of contralateral breast cancer (14 vs. 26). A third trial randomly assigned 4,742 women who had already received 2 years of adjuvant tamoxifen. Women either continued the tamoxifen or switched to exemestane. After 2.4 years' median follow-up, the women assigned to receive exemestane had a decreased risk of local or metastatic recurrence and a decreased risk of new primary contralateral breast cancer (9 vs. 20).
An RCT has reported the effect of aromatase inhibitors in preventing invasive breast cancer among women who have no history of breast cancer. In this study, 4,560 women aged 35 years and older who had at least one risk factor (e.g., women aged 60 years and older or those having a Gail 5-year risk >1.66% or a history of DCIS with mastectomy) were randomly assigned to receive exemestane 25 mg daily or a placebo. After 35 months median follow-up, 32 women of the 2,275 in the placebo group had been diagnosed with invasive breast cancer, compared with 11 women in the exemestane group (HR, 0.35; 95% CI, 0.18–0.70; NNT, about 100 for 35 months). There was a small increase in adverse effects in the exemestane group compared with the placebo group, primarily in hot flashes (increase, 8%) and fatigue (increase, 2%). There was no difference in the occurrence of fractures or cardiovascular events. A second trial (IBIS-2) is under way.