Olufunmilayo I. Olopade, MD
Center for Clinical Cancer Genetics
Professor, Department of Medicine
University of Chicago Medical Center
Chicago, Illinois
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| Olufunmilayo I. Olopade, MD |
The cause of breast cancer remains unknown in the majority of patients but epidemiologic studies have identified numerous risk factors, some of which are modifiable. A family history of breast cancer is one of the strongest risk factors, particularly when the diagnosis was made in multiple first-degree relatives and at young ages. In addition, a history of bilateral breast cancer in a first-degree relative further increases the risk. About 5%--10% of breast cancer cases are due to inheritance of highly penetrant mutations in breast cancer susceptibility genes, such as BRCA1 and BRCA2 genes.
Women with a history of prior invasive breast cancer or a history of non-invasive breast lesions, such as atypical hyperplasia and lobular carcinoma in situ (LCIS), carry an increased risk for invasive breast cancer. Moderate alcohol consumption and previous exposure to radiation, especially in survivors of childhood Hodgkin's disease, are also important risk factors. Early menarche and late menopause are weak risk factors. The effect of hormone replacement therapy or oral contraceptives on breast cancer risk has been controversial. However, prolonged use (> 5 years) of estrogen combined with progestins has been associated with increased breast cancer risk.
Considering the high prevalence of breast cancer, and the recent advances in chemoprevention or early detection of the disease, it is important to screen for the known risk factors so that women at high risk can be offered appropriate management options. Every woman with a family history of breast cancer requires a careful risk assessment and calculation of her lifetime risk of breast cancer.
Mutations in BRCA1 and BRCA2 predict probabilities of breast cancer by age 70 of 45%--87% and 26%--84%, respectively, making these the strongest known predictors of breast cancer. The lifetime risks of ovarian cancer for BRCA1 and BRCA2 mutation carriers are 16%--63% and 10%--27% respectively.(1--3) Genetic counseling and testing for breast cancer susceptibility genes, when appropriate, should be offered and provided as part of a comprehensive risk assessment plan.
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Women who are found to be at high-risk for hereditary breast cancer may be interested in prophylactic surgery to reduce their risks. These women, including BRCA1 and BRCA2 carriers, can reduce their risk of breast cancer > 90% following prophylactic mastectomy. The results of the first prospective study of women with BRCA1 and BRCA2 mutations showed that of 139 women with BRCA1 and BRCA2 mutations, 76 chose prophylactic bilateral mastectomy to reduce breast cancer risk; the remaining women chose a surveillance protocol consisting of a monthly breast self-examination (BSE), a semiannual breast examination by a healthcare professional, and annual mammography. Beginning in 1995, annual magnetic resonance imaging (MRI) was offered. With a follow up period of about 3 years, no breast cancers were observed in the 76 women who underwent bilateral prophylactic mastectomy, while eight cancers were detected in the surveillance group.(4) While prophylactic mastectomy is efficacious, it is only a minority of high-risk women who choose this option for risk reduction. Research into alternative methods for risk reduction are urgently needed.
The degree of risk reduction after prophylactic bilateral salpingo-oophorectomy for women with either strong family histories or germ-line BRCA mutation carriers has recently been demonstrated in two 2002 studies (Table 1).(5,6) Prophylactic oophorectomy appears to serve the dual purposes of eliminating the 'at risk' ovarian epithelium and decreasing breast cancer risk by reducing blood estradiol levels in premenopausal women. In a study that included 170 BRCA1 and BRCA2 mutation carriers >- 35 years and who were offered the opportunity to enroll in a prospective follow-up study after receiving genetic test results, the 5-year cancer-free survival estimates for healthy BRCA1 and BRCA2 mutation carriers who had prophylactic bilateral salpingo-oophorectomy was 94% compared to 69% for mutation carriers who chose surveillance. The surgical complication rate appears to be minimal--only four of the 98 (4.1%) women had any surgical complications.(5)
Table 1. Bilateral Salpingo-oophorectomy In BRCA Mutation Carriers
