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Breast Cancer: Overview and Risk Factors

One in 9 women in North America will be diagnosed with invasive breast cancer during her lifetime.1 Breast cancer is the most commonly diagnosed cancer in women, constituting about one third of all cancers. It is second only to lung cancer in cause of cancer death in women. The incidence of breast cancer in men is about 1% the rate in women. In both genders, the incidence increases with age. Most of the cancers are invasive at the time of diagnosis; only about 20% represent carcinoma in situ. More than 85% of the invasive tumors are infiltrating ductal carcinoma. Other histological types are infiltrating lobular, medullary, mucinous, and tubular carcinomas.

Risk Factors

Individuals in higher socioeconomic status (SES) categories generally have greater risk of developing breast cancer--as high as double the incidence in comparison with the lowest SES. The mediating factor is believed to be differing reproductive patterns in various SES groupings.2 Breast cancer incidence, aggressiveness, and mortality are higher in African American women, compared with whites.3-5

The role of oral contraceptives in breast cancer risk remains unsettled. The effect, if any, is very small.6-8 Breast cancer risk is not associated with induced abortion.9-12 Most studies have not shown increased risk from silicone breast implants, electromagnetic fields, electric blankets, hair dyes, or organochlorines.13

The following are widely accepted breast cancer risk factors:

Age. Incidence increases sharply until age 45 to 50 years. Incidence continues to increase with age after menopause, but at a slower rate.14 The rate of increase in incidence flattens in later years, and declines near age 80.15 Mean age at diagnosis is 65 years.

Family history. Risk increases with an increasing number of first-degree relatives with breast cancer history.

Genetic factors. The presence of BRCA1 or BRCA2 gene mutations increases breast cancer risk.

Reproductive events. These include early menarche, late menopause, older age at first birth, nulliparity, and lower parity.

Radiation exposure.

The following factors are also associated with breast cancer risk and may play etiologic roles:

Shorter duration of breast-feeding. Several cohort and case-control studies show protective benefits of breast-feeding. A multinational case-control study of nearly 150,000 women showed a decreased risk of 4.3% for each year of breast-feeding and 7% for each pregnancy.16

Obesity. Elevated estrogen levels, presumably due to peripheral aromatization of androstenedione to 1-estrone in adipose tissue, may increase breast cancer risk in overweight postmenopausal women.17

Higher endogenous serum estrogen concentrations. Women with higher concentrations of estrogen in their blood have a higher risk of developing breast cancer.18 In a clinical trial with 7,705 women, those whose estradiol concentrations were in the highest tertile had a relative risk of 2.07 for invasive postmenopausal breast cancer, compared with women with lower estradiol concentrations.19

Proliferative benign breast disease (with or without atypia).

Ovarian cancer.

Previous breast cancer. A first breast cancer may increase risk for subsequent unrelated breast cancer.20

Hormone replacement therapy (HRT). The Women's Health Initiative (WHI) trial showed a higher risk of breast cancer (RR=1.24) among women taking a combined estrogen-progesterone preparation for approximately 5 years, in comparison with those who used a placebo.21 Unopposed estrogens may have a lesser risk in comparison with combination HRT for eligible women, but this treatment carries other risks, such as thromboembolism. Studies link HRT to lobular cancers.22,23 The incidence of such cancers doubled from 1987 to 1999, without significant change in ductal cancer incidence.1 HRT also accelerates growth in estrogen and progesterone receptor-positive tumors.

Elevated blood glucose. The Nurses' Health Study found that postmenopausal women with diabetes had a slightly greater risk for breast cancer.24 Other studies have found greater risk for breast cancer in nondiabetic women with higher levels of fasting glucose.25,26

Factors associated with reduced risk include sunlight exposure (increasing vitamin D production) and physical activity.

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Breast Cancer: Diagnosis and Treatment >>