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Breast Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Description of Evidence

Incidence of Outcomes Per 1,000 Women

TamoxifenRaloxifeneRR, 95% CI
CI = confidence interval; RR = relative risk; VTE = venous thromboembolism.
Invasive breast cancer4.34.411.02, 0.82–1.28
Noninvasive breast cancer1.512.111.4, 0.98–2.00
Uterine cancer2.01.250.62, 0.35–1.08
VTE3.82.60.7, 0.68–0.99
Cataracts12.39.720.79, 0.68–0.92
Incidence of Symptoms (0–4 scale)
Favor Tamoxifen
Dyspareunia0.680.78P < .001
Musculoskeletal problems1.101.15P = .002
Weight gain0.760.82P< .001
Favor Raloxifene
Vasomotor symptoms0.960.85P < .001
Bladder control symptoms0.880.73P < .001
Leg cramps1.100.91P < .001
Gynecologic problems0.290.19P < .001

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.[104] 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.[105] 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.[106] 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).

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