What is the role of tamoxifen and raloxifene for the reduction of breast cancer risk?

Updated: Oct 24, 2019
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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Answer

Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, are approved for reduction of breast cancer risk in high-risk women. Two NSABP trials (P1 and P2) showed that tamoxifen reduced the risk of DCIS and invasive breast cancer by 30-50%. In the NSABP P2 prevention trial, raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer but was 30% less effective than tamoxifen in reducing the risk of DCIS.

ASCO has updated its practice guidelines regarding pharmacologic intervention (eg, tamoxifen, raloxifene, and aromatase inhibitors) for breast cancer risk reduction. [164] Some of the highlights of the expert panel’s literature review are as follows.

Tamoxifen use for 5 years reduces risk of breast cancer for at least 10 years in premenopausal women, particularly ER-positive invasive tumors. Women 50 years or younger have few adverse effects with tamoxifen, and vascular/vasomotor adverse effects do not persist after treatment.

As noted earlier, in an analysis that used pooled observational cohort data from 3 studies and included 1583 BRCA1 and 881 BRCA2 mutation carriers, adjuvant tamoxifen reduced the risk for contralateral breast cancer recurrences in women who carry these mutations. [132, 133]

Tamoxifen and raloxifene are equally effective in reducing the risk of ER-positive breast cancer in postmenopausal women. Raloxifene is associated with lower rates of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen is. The evidence does not allow determination of whether either agent decreases mortality from breast cancer.

Exemestane, an aromatase inhibitor, has also been found to be effective at reducing the incidence of invasive breast cancers in postmenopausal women at moderately increased breast cancer risk. In the NCIC- led MAP.3 trial, exemestane decreased the incidence of invasive breast cancer by 65% and that of invasive plus in situ breast cancer by 53% as compared with placebo. [165] Arthritis and hot flashes were more common in women treated with the aromatase inhibitor.


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