Risk assessment and risk reduction strategies: overview.

Abstract #MS1-1 In this mini-symposium, we will address the major risk factors for breast cancer, current risk prediction tools, and measures to reduce risk in those women deemed at high risk. Those factors that convey a significantly increased risk of breast cancer (e.g. relative risk greater than 4.0) include: strong family history of breast cancer (i.e. early onset of disease, multiple relatives with disease, including BRCA1/2 carriers); atypical hyperplasia on benign biopsy; older age; and dense breast tissue. Multiple other features are recognized as contributing to breast cancer risk but to a lesser degree. These include having a family history of breast cancer but not with a hereditary pattern (RR approximately 2.0), benign breast disease (RR 1.5), multiple reproductive factors including early menarche, late menopause, current or recent estrogen plus progesterone use, current OC use (all with relative risks in the 1.2-1.3 range); and alcohol use (e.g. 3 drinks per day) (RR∼1.3). Numerous other features such as induced abortion and sedentary lifestyle have been reported to increase risk of breast cancer but to a very minor degree and results are not consistent. Several risk prediction models for breast cancer focus on an individual9s likelihood of carrying a hereditary predisposition to the disease (e.g. Frank, Couch, Shattuck-Eidens, Parmigiani, BRCAPRO, BOADICEA, Claus). Outside of the hereditary setting, the most widely used tool is the Gail model. Features incorporated in the Gail model include age, family history, number of breast biopsies, age at menarche, age at first live birth, and the presence of atypia on a benign biopsy. While the Gail model has been shown to be calibrated in predicting number of breast cancers likely to develop in groups of women, its discriminatory accuracy in predicting risk for individual women is limited. This limitation is not well appreciated by many clinicians. Regarding options for surgical risk reduction in high risk individuals, several studies examined the efficacy of both bilateral and contralateral mastectomy in women at increased risk for breast cancer, including BRCA1/2 carriers. Results consistently show a greater than 90% reduction in risk of subsequent breast cancer. A study by the Cancer Research Network (6 HMOs) examined the impact of contralateral PM on mortality from breast cancer and showed reduced death from breast cancer with CPM (HR 0.57 [0.45-0.72]). Studies of risk-reducing salpingo-oophorectomy (RRSO) in BRCA carriers have shown dramatic reductions in risk of subsequent ovarian/peritoneal cancer, providing approximately 90% protection. The reduction in breast cancer risk after RRSO is seen only when the oophorectomy is performed in premenopausal women. Recent data on 368 BRCA1 and 229 BRCA2 carriers from a multicenter study show a differential effect on breast cancer risk following RRSO by mutation type. The hazard ratio for risk of breast cancer in BRCA2 carriers was 0.28 (0.08-0.92) (p 0.04) but for BRCA1 carriers was 0.61 (0.30-1.22) (p 0.16). This appeared to be due to the preponderance of ER-negative breast cancers in BRCA1 carriers, where no risk reduction with RRSO was seen. (N Kauff et al, JCO, 3/10/08) Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr MS1-1.