Risk factors for breast cancer

Risk factors for breast cancer may be divided into preventable and non-preventable. Their study belongs in the field of epidemiology. Breast cancer, like other forms of cancer, can result from multiple environmental and hereditary risk factors. The term environmental, as used by cancer researchers, means any risk factor that is not genetically inherited. For breast cancer, the list of environmental risk factors includes the individual person's development, exposure to microbes, "medical interventions, dietary exposures to nutrients, energy and toxicants, ionizing radiation, and chemicals from industrial and agricultural processes and from consumer products...reproductive choices, energy balance, adult weight gain, body fatness, voluntary and involuntary physical activity, medical care, exposure to tobacco smoke and alcohol, and occupational exposures, including shift work" as well as "metabolic and physiologic processes that modify the body's internal environment." Some of these environmental factors are part of the physical environment, while others (such as diet and number of pregnancies) are primarily part of the social, cultural, or economic environment. Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is most often unknowable. Epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. Approximately 5% of new breast cancers are attributable to hereditary syndromes, and well-established risk factors accounts for approximately 30% of cases. A 2024 review found that there is a convincing association between increased breast cancer risk with high BMI and weight gain in postmenopausal women and a decreased risk from high fiber intake and high sex hormone-binding globulin levels.

Age

The risk of getting breast cancer increases with age. A woman is more than 100 times more likely to develop breast cancer in her 60s than in her 20s. The risk over a woman's lifetime is, according to one 2021 review, approximately "1.5% risk at age 40, 3% at age 50, and more than 4% at age 70." In the United States, about one in eight women (~13%) and one in 800 men (~0.13%) will be diagnosed with breast cancer at some point during their lives. These numbers can vary depending on the location one grows up in, as numerous environmental factors can increase or decrease risk. Though the probability of breast cancer increases with age, breast cancer tends to be more aggressive in younger people.

Sex Male individuals have a much lower risk of developing breast cancer than females. In developed countries, about 99% of breast cancer cases are diagnosed in female patients; in a few African countries, which represent the highest incidence of male breast cancer, males account for 5–15% of cases. The rate of male breast cancer appears to be rising somewhat. Male breast cancer patients tend to be older than female ones. They are more likely to be diagnosed with hormone-receptor positive tumors, with about six out of seven cases being estrogen-receptor positive. The overall prognosis is worse for male than for female patients.

Heredity

The United Kingdom, being a member of the International Cancer Genome Consortium, is leading efforts to map breast cancer's complete genome.

BRCA1 and BRCA2 In 5% of breast cancer cases, there is a strong inherited familial risk. Two autosomal dominant genes, BRCA1 and BRCA2, account for most of the cases of familial breast cancer. Women who carry a harmful BRCA mutation have a 60% to 80% risk of developing breast cancer in their lifetimes. Other associated malignancies include ovarian cancer and pancreatic cancer. If a mother or a sister was diagnosed breast cancer, the risk of a hereditary BRCA1 or BRCA2 gene mutation is about two-fold higher than those women without a familial history. Commercial testing for BRCA1 and BRCA2 gene mutations has been available in most developed countries since at least 2004. In addition to the BRCA genes associated with breast cancer, the presence of NBR2, near breast cancer gene 1, has been discovered, and research into its contribution to breast cancer pathogenesis is ongoing.

Other genes Hereditary non-BRCA1 and non-BRCA2 breast tumors (and even some sporadic carcinomas) are believed to result from the expression of weakly penetrant but highly prevalent mutations in various genes. For instance, polymorphism has been identified in genes associated to the metabolism of estrogens and/or carcinogens (Cytochrome P450, family 1, member A1, CYP1B1, CYP17A1, CYP19, Catechol-O-methyltransferase, N-acetyltransferase 2, Glutathione S-transferase Mu 1, GSTP1, GSTT, . . . ), to estrogen, androgen and vitamin D action (ESR1, AR, VDR), to co-activation of gene transcription (AIB1), to DNA damage response pathways (CHEK2, HRAS1, XRCC1, XRCC3, XRCC5). Sequence variants of these genes that are relatively common in the population may be associated with a small to moderate increased relative risk for breast cancer. Combinations of such variants could lead to multiplicative effects. Sporadic cancers likely result from the complex interplay between the expression of low penetrance genes (risk variants) and environmental factors. However, the suspected impact of most of these variants on breast cancer risk should, in most cases, be confirmed in large populations studies. Indeed, low penetrance genes cannot be easily tracked through families, as is true for dominant high-risk genes. Part of the hereditary non-BRCA1 and non-BRCA2 breast tumors may be associated to rare syndromes, of which breast cancer is only one component. Such syndromes result notably from mutations in TP53 (Li–Fraumeni syndrome), ATM (ataxia–telangiectasia), STK11/LKB1(Peutz–Jeghers syndrome), PTEN (Cowden syndrome). RAB11FIP1, TP53, PTEN and rs4973768 are also associated with increased risk of breast cancer. rs6504950 is associated with lower risk of breast cancer. Mutations in RAD51C confer an increased risk for breast and ovarian cancer.

Prior cancers People who have previously been diagnosed with breast, ovarian, uterine, or bowel cancer have a higher risk of developing breast cancer in the future. Mothers of children with soft-tissue sarcoma may have an increased risk of breast cancer.

Dietary factors The Western dietary pattern is associated with an increased risk of breast cancer.

Alcohol

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