Breast Cancer Risk Factors

The general consensus is that both breast cancer screening and prevention strategies should be tailored based on an individual’s risk assessment. At the 30th Annual Miami Breast Cancer Conference, held March 7–10 in Miami Beach, Florida, Debu Tripathy, MD, professor of clinical medicine at the Keck School of Medicine of the University of Southern California and coleader of the Women’s Cancer Program at the USC Norris Comprehensive Cancer Center and Hospital, discussed the risk factors for developing breast cancer.

The risk factors can be parsed into genetic and biological factors, and environmental and lifestyle factors that can be modified. Several breast cancer risk factors that can be modified have been identified. The modifiable risk factors include alcohol use and postmenopausal estrogen replacement use. Factors that have been shown to decrease breast cancer risk include breast-feeding, number of live births, and exercise. Estimates of potential cancer risk reduction from altering these factors are based on modeling. For example, modeling-based studies show that decreasing alcohol use, increasing physical activity, and lowering body mass index could lower relative risk of breast cancer by 21% to 24%. This relative risk translates to a 20-year absolute breast cancer risk reduction in women, age 65 and older, by 1.6% for most women and 3.2% for those women with a family history of breast cancer.

“Many of the modifiable risk factors can be applied to all women. Exercise particularly cannot only reduce risk, but also improves cardiovascular health and overall health,” said Tripathy. “There is good evidence that patients who exercise, especially at a younger age, and patients who maintain their body weight, especially after menopause, tend to have a lower risk of breast cancer.”

Still, there has not yet been a prospective exercise study definitive of proving risk reduction, and the only randomized prospective diet as prevention study, the Women’s Health Initiative, did not show an effect on breast cancer risk. This study, which included women aged 50 to 79, explored the link between a low-fat diet and breast cancer risk, but did not find that diet alone reduced risk.

Inherited genetic factors include BRCA and other susceptibility gene mutations. Hormonal endogenous exposure factors consist of bone density, age at first child delivery, and having more periods in a lifetime. Exogenous estrogen exposure is also a risk factor. “Women who take postmenopausal estrogen replacement, especially if they take it with progestin are at higher risk. We have not seen an increase in risk in women who take estrogen alone-in fact, this may lower risk,” said Tripathy. Breast density detected by mammogram is a strong predictor of risk. “Those patients with greater than 50% density tend to have almost a threefold increased risk, compared with those who have very low breast density,” said Tripathy. However, there is not a validated way to measure density in order to make specific changes in screening or prevention measures.

Screening recommendations still suggest women should begin to have mammograms at a certain age, regardless of risk factors. However, Tripathy pointed out that those women with more risk factors may begin to be screened earlier, but that we currently do not have established criteria for age-specific screening.

“The only risk factors that have an impact on clinical decision-making are strong family history and heritable mutations,” said Tripathy. These patients are recommended to undergo MRI screenings and even consider prophylactic mastectomy, while those with BRCA1 or BRCA2 mutations should have an oophorectomy following childbearing, as this appears to lower both breast and ovarian cancer mortality.