Implications of multigene testing for hereditary breast cancer in primary care

Table 1 Guidelines for hereditary breast cancer genetic assessment in a woman without a cancer diagnosis

Organization	Indications for genetic assessment referral
National Comprehensive Cancer Network[8]	Family history of any of the following: A known mutation in a cancer susceptibility gene within the family ≥ 2 breast cancer primaries in a single individual ≥ 2 individuals with breast cancer primaries on the same side of family ≥ 1 individual with invasive ovarian cancer primary First- or second-degree relative with breast cancer at age ≤ 45 yr Three or more of the following (especially if early onset): Pancreatic cancer, prostate cancer (Gleason score ≥ 7), sarcoma, adrenocortical carcinoma, brain tumors, endometrial cancer, thyroid cancer, kidney cancer, dermatologic manifestations and/or macrocephaly, hamartomatous polyps of gastrointestinal tract, diffuse gastric cancer (can include multiple primary cancers in same individual) Male breast cancer
United States Preventive Services Task Force[9]	Family history of any of the following: Breast cancer diagnosis before age 50 yr Bilateral breast cancer Breast and ovarian cancer Breast cancer in ≥ 1 male family member Multiple cases of breast cancer in the family ≥ 1 family member with 2 primary types of BRCA-related cancer Ashkenazi Jewish ethnicity OR use of a familial risk stratification tool, such as the Ontario Family History Assessment Tool, Manchester scoring system, Referral Screening Tool, Pedigree Assessment Tool, and Family History Screen 7, to determine need for genetic counseling
American Society of Clinical Oncology[7,10]	When all 3 criteria are met: The individual being tested has a personal or family history suggestive of genetic cancer susceptibility The genetic test can be adequately interpreted The test results have accepted clinical utility
National Society of Genetic Counselors[5,11] and American College of Medical Genetics and Genomics[11]	If patient or any of their first-degree relatives meet one of the following criteria: Breast cancer diagnosis at age ≤ 50 yr Triple-negative breast cancer diagnosis at age ≤ 60 yr ≥ 2 primary breast cancers in the same person Ashkenazi Jewish ancestry and breast cancer at any age ≥ 3 cases of breast, ovarian, pancreatic, and/or aggressive prostate cancer in close relatives, including the patient Breast cancer and one additional Li-Fraumeni Syndrome tumor in the same person or in two relatives, one diagnosed at age ≤ 45 yr Breast cancer and ≥ 1 Peutz-Jeghers polyp in the same person Lobular breast cancer and diffuse gastric cancer in the same person Lobular breast cancer in one relative and diffuse gastric cancer in another, one diagnosed at age < 50 yr Breast cancer and 2 additional Cowden syndrome criteria in the same person
American College of Obstetricians and Gynecologists[12]	Women with greater than an approximately 20%-25% chance of having an inherited predisposition to breast and ovarian cancer are recommended for genetic counseling referral, including: Women with a close relative with known BRCA1 or BRCA2 mutations In women with greater than an approximate 5%-10% chance of having an inherited predisposition to breast and ovarian cancer, genetic counseling referral may be helpful, including those with a close relative that has: Breast cancer at age ≤ 40 yr Ovarian cancer, primary peritoneal cancer, or fallopian tube cancer of high grade, serous histology at any age Bilateral breast cancer (particularly if the first case of breast cancer was diagnosed at age ≤ 50 yr) Breast cancer at age ≤ 50 yr and a close relative with breast cancer at age ≤ 50 yr Ashkenazi Jewish ancestry with breast cancer at age ≤ 50 yr Breast cancer at any age and 2 or more close relatives with breast cancer at any age (particularly if at least one case of breast cancer was diagnosed at age ≤ 50 yr)