Numerous studies have documented factors that increase the relative risk for breast cancer (see Box 31.1).
Age is the single largest risk factor for developing breast cancer.A majority of breast cancer cases occur in women over the age of 50. Stratified studies relate risk with age (by decades), and show that the risk for developing breast cancer increases as a woman gets older. For example, a woman has a 1.4% chance of being diagnosed with breast cancer between the ages of 40 and 49, compared to 3.7% between the ages of 60 and 69. When stratified by race, white women are more likely to be diagnosed with breast cancer compared to age-matched women of Latin, Asian, or African American descent.
Women who have first-degree relatives (parent, sibling, or offspring) with breast cancer have a higher risk than the general population.
If a woman before the age of 40 is diagnosed with breast cancer, evaluating for genetic mutations that predispose individuals to cancer is reasonable.
The two most commonly discussed genetic mutations linked to breast cancer are the BRCA1 and BRCA2 gene mutations.
BRCA1 is a gene located on the 17q21 chromosome.This mutation is associated with nearly half of the early-onset breast cancers and approximately 90% of hereditary ovarian cancers. BRCA2 is a gene located on the 13q12–13 chromosome. This mutation has a lower incidence of early-onset breast cancers (35%) and much lower risk of ovarian cancer, compared to BRCA1.
In general, women who have an early age of menstrual onset (before the age of 12) and transition through menopause after age 55 are at increased risk of breast cancer. Delayed childbearing and nulliparity also increase the chance of breast cancer.
Breast tissue of young women (along with the bone mar-row and infant thyroid) is highly susceptible to the cancer-causing effects of ionizing radiation. Women who have received a sufficiently large dose of radiation (radiation therapy to treat Hodgkin disease or an enlarged thymus gland) are at risk for radiation-induced breast cancer. The relationship between dose of radiation and risk of cancer is directly linear, although the threshold is unclear. Thus far, epidemiologic studies have not detected a significant increase in cancer risk below a cumulative dose of about 20 cGy. To put this dose into perspective, a typical mam-mogram results in a breast tissue dose of about 0.3 cGy. The time needed for a radiation-induced lesion to develop is about 5 to 10 years from exposure.
It is believed that women with dense breast tissue are at increased risk for breast cancer. In addition, histologic biopsies finding atypical hyperplasia or lobular carcinoma in situ greatly increase the risk for breast cancer.
Being overweight after menopause has been linked to an increased risk for breast cancer. A possible mechanism in thisrelationship is that the increased peripheral conversion of androstenedione to estrone stimulates breast cancer development. Lack of exercise throughout life is linked to the increased risk of breast cancer through the associated risk of obesity.
Women who consume 2 to 4 alcoholic drinks per week have a 30% greater risk of dying from breast cancer than women who never drink. The exact mechanism of action is unclear, butresearchers speculate that alcohol consumption stimulates the growth and progression of breast cancer by inducing angiogenesis and increasing the expression of vascular endothelial growth factor (VEGF).