Risk factors for the development of breast cancer include; age over 50, increased exposure to estrogen over their lifetime, including early menarche, late menopause, family history of breast cancer, especially in a first-degree relative diagnosed before menopause. About 8% of all breast cancers are hereditary, and up to 50% of these are seen in patients with a BRCA1 and BRCA2 mutation. Hereditary breast cancers are more likely to present as bilateral cancers, present in women with multiple generations of breast cancer occurrences in their genealogy and premenopausal patients at the time of diagnosis. Note that when obtaining a patient's past family history, women from the paternal side of the family are also included when assessing the past medical history.
Breast cancer is hormone-dependent cancer. Consequently, women with the endogenous supply of estrogen via their ovaries or women who never receive estrogen therapy are at significantly lower risk of developing breast cancer. Breast cancer predominantly affects women relative to men, with a male to female ratio of 1:150. In all women, 3 notable events have a massive impact on the risk of developing breast cancer; age at onset of menses, age at full first term pregnancy, and age at menopause. Note that women who start their menses at age 16 only have approximately 50% of the risk of women who start their menstrual cycle at age 12. Likewise, early menopause at least 10 years before the median reported age of 52 years would significantly reduce the risk for breast cancer. It is important to recognize that whether menopause is naturally or surgically induced, the risk of developing breast cancer remains equally reduced. All women who give birth to their first child by age 18 will also have a 20-40% reduction in their risk of developing breast cancer.
The Li-Fraumeni syndrome is related to a tumor suppressor gene p53. Other genetic mutations related to breast cancer in women include; PTEN mutation, BRCA1, and BRCA2 genes. The BRCA1 gene has been linked to the increased occurrence of breast and prostate cancer in men and women. All patients diagnosed with a BRCA1 or BRCA2 mutation need to be counseled extensively about their risk of breast cancer and other malignancies, especially women of Ashkenazi Jewish descent.
In addition to the genetic risks associated with breast cancer, there has been a substantial difference in the reported breast cancer rates, which cannot be explained by genetic risk alone. Migrant women from various parts of the world who immigrate to the United States tend to have similar estrogen levels to women in the United States after a few years. However, their counterparts who remained in their country of origin have significantly lower estrogen levels. This suggests that nutritional influences on hormone levels may affect the risk of developing breast cancers. Note that the role of diet in determining the risk of breast cancer remains very controversial. Thus, further research is needed on this topic.
It is imperative that clinical providers in the US fully understand the relationship between exogenous hormone administration and the risk of developing breast cancer, given that millions of American women use postmenopausal hormone supplementation and oral contraceptives each year. Most research examining the relationship between oral contraceptives and breast cancer suggests a mildly increased risk of developing breast cancer using oral contraceptives. On the other hand, there is a well-documented decreased risk of endometrial and ovarian cancers using oral contraceptives or postmenopausal hormone replacement therapy.
The Women's Health Initiative study showed that the use of both estrogen plus progesterone resulted in a clear increased risk of developing breast cancer while reducing the risk of colorectal cancer and bone fractures.
Prior radiation exposure is a significant risk for the development of breast cancer. Women who received radiation therapy before age 30 to treat certain malignancies or radiation exposure from radiologic procedures have a significantly increased risk of developing breast cancer. Radiation exposure after the age of 30 does not demonstrate an increased risk of developing breast cancer.