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 who was diagnosed prior to menopause. About 8% of all breast cancers are hereditary, and up to 50% of these are seen in patients with a BRCA 1 and BRCA 2 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 as well as in patients who are premenopausal 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.1
Breast cancer is a hormone-dependent cancer. Consequently, women with an 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, there are 3 notable events that 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 have only approximately 50% of the risk of women who start their menstrual cycle at age 12. Likewise, early menopause at least 10 years prior to the median reported age of 52 years will 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 by at least 35%.2 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 mutation in a tumor suppressor gene p53. Other genetic mutations related to the occurrence of breast cancer in women include; PTEN mutation, BRCA1 and BRCA 2 genes amongst others. Note that the BRCA 1 gene has been linked to the increased occurrence of breast and prostate cancer in men and women. All patients diagnosed with a BRCA1 or BRCA 2 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 rates of breast cancer 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 there may be nutritional influences on hormone levels which in turn 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 post-menopausal hormone supplementation and oral contraceptives each year. Most research examining the relationship between oral contraceptives and breast cancer suggests that there is mildly increased risk of developing breast cancer with the use of oral contraceptives. On the other hand, there is a well-documented decreased risk of endometrial and ovarian cancers with the use of oral contraceptives or post-menopausal 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. The risk of breast cancer was nearly doubled with a 7-year use of hormone replacement therapy. Data from a parallel WHI trial showed that women who only had estrogen replacement therapy alone did not have a significant increase in the risk of breast cancer.1
Prior radiation exposure is a significant risk for the development of breast cancer. Women who received radiation therapy before age 30 for the treatment of 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.