Anastrozole May Decrease Risk of Breast Cancer in High-Risk Postmenopausal Women

EBM Focus - Volume 9, Issue 14

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Reference: Lancet 2014 Mar 22;383(9922):1041 (level 2 [mid-level] evidence)

Breast cancer is the most common type of cancer affecting women, with more than 230,000 new cases estimated in the United States in 2013 (CA Cancer J Clin 2013 Jan;63(1):11). The United States Preventive Services Task Force (USPSTF) recommends that women at increased risk of breast cancer and low risk for adverse medication effects be offered tamoxifen 20 mg daily for 5 years or raloxifene 60 mg daily for 3-4 years to reduce their risk of breast cancer (USPSTF Grade B, Ann Intern Med 2013 Sep 24 early online full-text). This recommendation is partially based on a recent systematic review of 7 randomized trials showing that tamoxifen or raloxifene may reduce the incidence of invasive breast cancer by 7-9 cases per 1,000 women over 5 years compared with placebo (Ann Intern Med 2013 Apr 16;158(8):604). In addition, the MAP.3 trial recently showed that the aromatase inhibitor exemestane may reduce the incidence of invasive breast cancer among high-risk postmenopausal women (N Engl J Med 2011 Jun 23;364(25):2381 full-text). Now, a randomized trial compares anastrozole to placebo in 3,864 postmenopausal women aged 40-70 years at high risk of breast cancer.

Women were randomized to anastrozole 1 mg orally once daily vs. placebo. All women had at least 1 risk factor for breast cancer, including a first-degree relative with breast cancer, at least 2 second-degree relatives with breast cancer, at least 2 first- or second-degree relatives with ovarian cancer, prior atypical ductal or lobular hyperplasia in benign lesion, lobular carcinoma in situ, or prior estrogen receptor-positive ductal carcinoma in situ within previous 6 months and completion of adequate local treatment. At baseline, 47% of women were receiving hormone replacement therapy. All women had mammograms at least once every 2 years during median 5 years of follow-up. The 5-year adherence rate was 70% overall, and slightly lower with anastrozole vs. placebo (68% vs. 72%, p = 0.0047).

The incidence of breast cancer (either invasive cancer or noninvasive ductal carcinoma in situ) was 2% with anastrozole vs. 4% with placebo (p < 0.0001, NNT 50). Similarly, anastrozole was associated with a lower rate of invasive estrogen receptor-positive cancer (1% vs. 2%, p = 0.001, NNT 100), and ductal carcinoma in situ in (0.3% vs. 1%, p = 0.009, NNT 143), but there were no differences in invasive estrogen receptor-negative cancer (1% in each group) or mortality (1% in each group). The rate of non-breast cancer was 2% with anastrozole vs. 4% with placebo (p = 0.005, NNT 50). Hot flushes or night sweats occurred in 57% with anastrozole vs. 49% with placebo (p< 0.0001, NNH 12). Treatment discontinuation due to adverse events occurred in 20% with anastrozole vs. 15% with placebo (no p value reported).

This trial demonstrates that anastrozole is associated with modest reductions in the incidence of breast cancer among high-risk postmenopausal women. These results add another option in addition to selective estrogen receptor modulators tamoxifen and raloxifene and the aromatase inhibitor exemestane for prevention of breast cancer. However, none of these trials have yet shown a benefit for preventative therapy in breast-cancer related mortality or all-cause mortality. In light of this, the decision to offer such therapies for reducing the incidence of breast cancer in high-risk postmenopausal women must be carefully balanced by the potential for increased adverse events.

For more information see the Chemoprevention of breast cancer topic in DynaMed.