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In the United States, breast cancer is the most commonly diagnosed cancer among women and is second only to lung cancer as the leading cause of cancer-related deaths in women (1). In 2013, approximately 234,000 women will be diagnosed with breast cancer in the United States and 40,000 women will die of the disease. An estimated 2200 men will be diagnosed with breast cancer this year. In the United States, the lifetime probability of developing breast cancer is one in eight (2). Since 1975, breast cancer mortality rates have declined. This decline in mortality is largely attributable to increased use of screening mammography, as well as advances in adjuvant therapy.
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Approximately half of women diagnosed with breast cancer have identifiable risk factors besides age and gender. There are specific hormonal and reproductive factors that may increase risk for breast cancer. In addition, a number of lifestyle, diet, and environmental factors confer an increased risk of breast cancer. A personal or family history of breast cancer, as well as a history of benign breast disease, also increases a woman's risk of developing breast cancer.
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ENDOGENOUS ESTROGEN EXPOSURE/REPRODUCTIVE FACTORS
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It is known that hormonal and reproductive factors influence breast cancer risk. Prolonged exposure to estrogen is associated with an increased risk of breast cancer (3). Estrogen exposure is increased by early menarche, late menopause, and nulliparity, or greater than 30 years of age at birth of the first child. Breastfeeding confers a protective effect on breast cancer risk.
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In postmenopausal women, the main source of estrogen is dehydroepiandrosterone (DHEA), which is produced in the adrenal gland and subsequently metabolized to estradiol and estrone. In postmenopausal women, higher serum levels of estrogen correlate with increased breast cancer risk. Higher bone mineral density and increased mammographic breast density, perhaps surrogates for increased long-term exposure to endogenous estrogen, have also been associated with increased breast cancer risk.
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EXOGENOUS ESTROGEN EXPOSURE
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The role of exogenous estrogen on breast cancer risk is complicated and has been extensively studied. It is generally accepted that past oral contraceptive (OC) use does not result in any significant increase in breast cancer risk in women over 40 years of age. The data on OC use in women with a family history of breast cancer are conflicting. One study suggested that there was an increased risk of breast cancer among women who took OC prior to 1975 (higher dose formulations) and who also had a first degree relative with breast cancer.
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Another study, the Women's Health Initiative (WHI) evaluation of estrogen replacement therapy (ERT) in postmenopausal women, supports a modestly increased associated risk of breast cancer in women taking combined estrogen and progestin therapy (4). Risk appears to rise with increasing duration of ...