and -Associated Hereditary Breast and Ovarian Cancer

CLINICAL CHARACTERISTICS

and associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a pathogenic variant. The risk of developing an associated cancer varies depending on whether HBOC is caused by a or pathogenic variant

DIAGNOSIS/TESTING: The diagnosis of - and -associated HBOC is established in a proband by identification of a heterozygous germline pathogenic variant in or on molecular genetic testing.

MANAGEMENT

Treatment of breast cancer per oncologist with consideration of bilateral mastectomy as a primary surgical treatment of breast cancer because of elevated rate of ipsilateral and contralateral breast cancer; PARP inhibitors may be considered in and -related tumors. Melanoma treatment per dermatologist and oncologist. Prophylactic bilateral mastectomy, prophylactic oophorectomy, and chemoprevention (e.g., tamoxifen) have been used for breast cancer prevention, but have not been assessed by randomized trials in high-risk women. Prophylactic salpingectomy followed by delayed oophorectomy or salpingo-oophorectomy for ovarian cancer prevention. Breast cancer screening in women relies on a combination of monthly breast self-examination, annual or semiannual clinical breast examination, annual mammography, and breast MRI. Annual transvaginal ultrasound and serum CA-125 concentration beginning at age 35 years may be considered for ovarian cancer screening. However, this screening has not been effective in detecting early-stage ovarian cancer, either in high-risk or average-risk women. For men, breast cancer screening includes breast self-examination education and training and annual clinical breast examination beginning at age 35. Annual serum prostate-specific antigen and digital rectal exam screening should begin at age 40 in men heterozygous for a pathogenic variant and should be considered in men heterozygous for a pathogenic variant. Screening for melanoma should be individualized based on the family history. Screening of asymptomatic individuals for pancreatic cancer is not generally recommended. Once a cancer-predisposing or germline pathogenic variant has been identified in a family, testing of at-risk relatives can identify those family members who also have the familial pathogenic variant and thus need increased surveillance and specific treatments when a cancer is identified.

GENETIC COUNSELING

and associated HBOC is inherited in an autosomal dominant manner. The vast majority of individuals with a or pathogenic variant inherited it from a parent. However, because the penetrance of breast, ovarian, and other cancers associated with pathogenic variants in and is less than 100%, not all individuals with a or pathogenic variant have a parent affected with cancer. The offspring of an individual with a or germline pathogenic variant have a 50% chance of inheriting the pathogenic variant. Once a cancer-predisposing or germline variant has been identified in a family, prenatal and preimplantation genetic testing are possible.