Clinical Management of BRCA Mutation Carriers
A substudy of the NSABP-P-1 trial evaluated the effectiveness of tamoxifen in preventing breast cancer in BRCA1/BRCA2 mutation carriers older than 35 years. BRCA2-positive women benefited from tamoxifen to the same extent as BRCA1/BRCA2 mutation-negative participants; however, tamoxifen use among healthy women with BRCA1 mutations did not appear to reduce breast cancer incidence. These data must be viewed with caution in view of the small number of mutation carriers in the sample (8 BRCA1 carriers and 11 BRCA2 carriers).
Level of evidence: 1
In contrast to the very limited data on primary prevention in BRCA1 and BRCA2 mutation carriers with tamoxifen, several studies have found a protective effect of tamoxifen on the risk of contralateral breast cancer.[76,77,78] In one study involving approximately 600 BRCA1/BRCA2 mutation carriers, tamoxifen use was associated with a 51% reduction in contralateral breast cancer. An update to this report examined 285 BRCA1/BRCA2 mutation carriers with bilateral breast cancer and 751 BRCA1/BRCA2 mutation carriers with unilateral breast cancer (40% of these patients were included in their initial study). Tamoxifen was associated with a 50% reduction in contralateral breast cancer risk in BRCA1 mutation carriers and a 58% reduction in BRCA2 mutation carriers. Tamoxifen did not appear to confer benefit in women who had undergone an oophorectomy, although the numbers in this subgroup were quite small. Another study involving 160 BRCA1/BRCA2 mutation carriers demonstrated that tamoxifen use following treatment of breast cancer with lumpectomy and radiation was associated with a 69% reduction in the risk of contralateral breast cancer. These studies are limited by their retrospective, case-control designs and the absence of information regarding estrogen-receptor status in the primary tumor.
The STAR trial (NSABP-P-2) included more than 19,000 women and compared 5 years of raloxifene with tamoxifen in reducing the risk of invasive breast cancer.  There was no difference in incidence of invasive breast cancer at a mean follow-up of 3.9 years; however, there were fewer noninvasive cancers in the tamoxifen group. The incidence of thromboembolic events and hysterectomy was significantly lower in the raloxifene group. Detailed quality of life data demonstrate slight differences between the two arms. Data regarding efficacy in BRCA1 or BRCA2 mutation carriers are not available.
The effect of tamoxifen on ovarian cancer risk was studied in 714 BRCA1 mutation carriers. All subjects had a prior history of breast cancer; use of tamoxifen was not associated with an increased risk of subsequent ovarian cancer (OR = 0.78, 95% CI, 0.46-1.33).
Level of evidence: 1
Pregnancy and Lactation
In the general population, breast cancer risk increases with early menarche and late menopause, and is reduced at early first full-term pregnancy. (Refer to the PDQ summary on Breast Cancer Prevention for more information.) In the Nurses' Health Study, these were risk factors among women who did not have a mother or sister with breast cancer. Among women with a family history of breast cancer, pregnancy at any age appeared to be associated with an increase in risk of breast cancer, persisting to age 70 years.