Management of an inherited predisposition to breast cancer
Genetic Predisposition to Disease
The woman described in the vignette is clearly at increased risk for breast cancer. Risk-prediction models based on family history indicate that her lifetime risk is 30 to 40%. BRCAPRO, the most commonly used model for predicting the presence of a mutation, indicates a 37% probability of detecting a BRCA mutation.5 BRCA testing should be offered to the patient's sister. Even if no mutation is found in the family, this young woman is still at increased risk for breast cancer, and mammography should begin by the age of 40 years or 5 to 10 years before the youngest age at which breast cancer was diagnosed in a family member, whichever is earlier. In women with a BRCA mutation, screening should begin by the age of 25 to 30 years. Although no studies have shown a mortality benefit, the American Cancer Society recommends MRI screening in addition to mammography for women with a BRCA mutation or for women who, like this patient, have a lifetime breast-cancer risk of at least 20 to 25% on the basis of family history.8 Ultrasonography and breast examination may increase detection rates slightly but at a cost of more false positive results and additional evaluations. Preventive mastectomy and salpingooophorectomy for BRCA mutation carriers are options that should be discussed with women who are at increased risk. Oophorectomy is performed after childbearing, since the greatest increase in the risk of ovarian cancer occurs later than that of breast cancer in BRCA mutation carriers.65 Risks and benefits of chemoprevention (e.g., with tamoxifen or raloxifene) should also be discussed. In many circumstances, patients may be referred to genetic counselors and physicians with expertise in clinical cancer genetics and with access to targeted prevention trials. Finally, the patient should be made aware of the inherited nature of breast-cancer risks and should be encouraged to refer family members forconsideration of genetic testing and of strategies for prevention and early detection.70 Copyright © 2007 Massachusetts Medical Society.
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