One study evaluated risk modifiers among 333 female carriers of a BRCA1 high-risk mutation. In women with known mutations of the BRCA1 gene, early age at first live birth and parity of three or more have been associated with a lowered risk of breast cancer. A relative risk (RR) of 0.85 was estimated for each additional birth, up to five or more; however, increasing parity appeared to be associated with an increased risk of ovarian cancer.[83,84] In a case-control study from New Zealand, investigators noted no difference in the impact of parity upon the risk of breast cancer between women with a family history of breast cancer and those without a family history.
Studies of the effect of pregnancy on breast cancer risk have revealed complex results and the relationship with parity has been inconsistent and may vary between BRCA1 and BRCA2 mutation carriers.[86,87,88] Parity has more consistently been associated with a reduced risk of breast cancer in BRCA1 mutation carriers.[86,87,88,89,90] Of note, neither therapeutic nor spontaneous abortions appear to be associated with an increased breast cancer risk.[88,91]
Level of evidence: 4aii
In the general population, breastfeeding has been associated with a slight reduction in breast cancer risk in a few studies, including a large collaborative reanalysis of multiple epidemiologic studies, and at least one study suggests that it may be protective in BRCA1 mutation carriers. In a multicenter breast cancer case-control study of 685 BRCA1 and 280 BRCA2 mutation carriers with breast cancer and 965 mutation carriers without breast cancer drawn from multiple-case families, among BRCA1 mutation carriers, breastfeeding for one year or more was associated with approximately a 45% reduced risk of breast cancer. No such reduced risk was observed among BRCA2 mutation carriers. A second study failed to confirm this association.
There is no consistent evidence that the use of oral contraceptives increases the risk of breast cancer in the general population. (Refer to the PDQ summary on Breast Cancer Prevention for more information.) In a meta-analysis of data from 54 studies, family history of breast cancer was not associated with any variation in risk associated with oral contraceptive use. Studies have demonstrated mixed results in BRCA1 and BRCA2 mutation carriers. Several small studies have reported a slight increased risk.[95,96] In addition, four larger, case-control studies have also been reported.[97,98,99,100] Three studies used matched cases and controls who were all BRCA mutation carriers.[97,100] Two studies found that there was an increased risk for BRCA1 mutation carriers associated with ever use and duration of use, especially when prior to a first full-term birth.[97,100] Duration of use and use before pregnancy were also associated with an increased risk in BRCA2 mutation carriers. In another study, these same risk factors were associated with an increased risk only in BRCA2 mutation carriers. Two studies found that use of birth control pills prior to 1975 was associated with an increased risk of breast cancer among BRCA1 mutation carriers,[97,100] although this was not seen in another study. One smaller study matched BRCA mutation carriers with breast cancer to population-based controls who were not BRCA tested. This study found a protective effect of birth control pills among BRCA1 mutation carriers.Table 9 summarizes the results of these studies.