Epidemiology, genetics, and risk evaluation of postmenopausal women at risk of breast cancer

1. Epidemiology, genetics, and risk evaluation of postmenopausal womenat risk of breast cancer Menopause: The Journal of The North American Menopause Society Vol. 15, No. 4, pp. 782/789 Jul-Aug, 2008

3. Classic Breast Cancer Risk Factors All women are at risk of breast cancer, and the single most important risk factor is age.

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6. Sclerosing adenosis increases the risk of breast cancer by approximately 70%.

7. 5% to 10% of proliferative lesions show cellular atypia, which increases the risk of breast cancer fivefold. Nearly 40% of women with a family history of breast cancer and atypical hyperplasia subsequently develop breast cancer.

8. LCIS (lobular carcinoma in situ) has generally been considered a risk indicator, conferring an increased rate of development of invasive carcinoma of approximately 1% to 2% per year, with a lifetime risk of 30% to 40%.

9. FAMILY HISTORY OF BREAST CANCERAND BRCA1 AND BRCA2 MUTATIONS • Genetic factors contribute to approximately 5% of all breast cancers, but to 25% of cases diagnosed before 30 years of age. • Having more relatives with breast cancer before age 50 increases the cumulative lifetime risk of developing the disease to almost 50% • The risk of breast cancer associated with either a BRCA1 or BRCA2 mutation is more than 200 times greater in individuals younger than age 40 but drops to 15-fold in the seventh decade of life. • High-grade DCIS is more common in BRCA1 mutation carriers than in patients without a mutation

10. MAMMOGRAPHIC DENSITY ANDCIRCULATING ENDOGENOUS HORMONE LEVELS • Levels of both circulating sex steroids and mammographic density are significantly and independently associated with breast cancer risk. • High mammographic density on a first examination is associated with a high rate of breast cancer that remains high even if breast density decreases in subsequent mammographic examinations. • Increased risk with elevated total estradiol, free estradiol, non-SHBG-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, DHEA, DHEA-S, and testosterone.

12. IMPACT OF DIET, EXERCISE,AND ENVIRONMENTAL FACTORS • Excess weight and weight gain in adult life are related to higher risk of postmenopausal breast cancer. • Weight loss after menopause is associated with substantially reduced risk. • Physical activity and the prevention of weight gain can improve survival after a breast cancer diagnosis. • The only well-established individual diet-related risk factor for breast cancer other than obesity is alcohol consumption. • Populations with high fat intakes generally have higher rates of breast cancer, but studies of individual women have not confirmed an association of high-fat diets with breast cancer risk. • Folic acid: dual effect? • Phytoestrogen: inconsistent.

13. QUANTITATIVE RISK ASSESSMENTAND THE GAIL MODEL • The average age at diagnosis of breast cancer among women in North America is 60 years, and the risk of developing breast cancer among these women is 1.67% in the 5 years between ages 60 and 65. • Women whose 5-year risk of developing invasive breast cancer is greater than 1.67% are considered to be at increased risk. • FDA used this risk level to define high-risk subjects who might consider the use of selective estrogen receptor modulators (tamoxifene or raloxifene) for reduction of breast cancer risk.