Other hormonal changes also influence breast cancer risk. Childbirth is followed by a transient increase in risk and then a long-term reduction in risk, which is greater for younger women.[14,16,17] In one study, women who experienced a first full-term pregnancy before age 20 years were half as likely to develop breast cancer as nulliparous women or women who underwent a first full-term pregnancy at age 35 years or older. Age at menarche also affects breast cancer risk. Women who experienced menarche at age 11 years or younger have about a 20% greater chance of developing breast cancer than women who experienced menarche at age 14 years or older. Women who experience late menopause also have increased risk. Reproductive risk factors may interact with more predisposing genotypes. In the Nurses' Health Study, the associations between age at first birth, menarche, and menopause and the development of breast cancer were observed only among women without a family history of breast cancer in a mother or sister. Breast-feeding is associated with a decreased risk of breast cancer.[21,22]
A number of studies suggest that endogenous estrogen and androgen levels are higher in women who develop breast cancer than in women who do not.[10,23,24] Methods shown to decrease endogenous estrogen include maintenance of ideal body weight (refer to the Obesity section of this summary for more information), adoption of a low-fat diet in postmenopausal women, and moderate exercise in adolescent girls. Whether such interventions will decrease breast cancer risk is worthy of study.
The inherited genetic profile of an individual influences susceptibility to mutagens and growth factors, which initiate or promote the carcinogenic process. Known genetic syndromes related to specific aberrant alleles account for approximately 5% of breast cancers. Identifying high-risk genes provides insight into breast cancer etiology and allows the development of preventive interventions for affected populations. (Refer to the PDQ summary on Genetics of Breast and Ovarian Cancer for more information.)
Women who inherit a deleterious mutation in BRCA1[27,28] or BRCA2 have an increased lifetime risk of breast cancer (which occurs at a younger age), ovarian cancer, and possibly colon cancer. Deleterious BRCA2 mutations are less common than BRCA1 mutations; BRCA2 mutations are also associated with male breast cancer, prostate cancer, pancreatic cancer, and lymphomas.
Women who carry an abnormal ataxia telangiectasia (ATM) gene may be at increased risk of breast cancer.
Factors Associated With Increased Risk of Breast Cancer
Exogenous hormone therapy (HT) after menopause is associated with increased breast cancer risk.
The Heart and Estrogen/Progestin Replacement Study  included an open-label follow-up of a randomized controlled trial (RCT) of estrogen and progestin therapy in 2,763 women (mean age 67 years) who had coronary heart disease. After a mean follow-up of 6.8 years, the relative risk [RR] for breast cancer was 1.27 (95% confidence interval [CI], 0.84-1.94). Though not statistically significant, the RR estimate is consistent with the much larger Women's Health Initiative (WHI) study.