Revised Figure 3, Lynch syndrome pedigree, to state that the pedigree shows some of the classic features of a family with Lynch syndrome, including affected family members with colon cancer or endometrial cancer, a young age at onset in some individuals, and incomplete penetrance; because the cancer risk is not 100%, individuals who have Lynch syndrome may not develop cancer, such as the mother of the female with colon cancer diagnosed at age 37 years in this pedigree.
Revised text about the Prediction of Mismatch repair gene Mutations (PREMM) model called PREMM5, an update of PREMM(1,2,6), which includes each of the five genes associated with Lynch syndrome, including PMS2 and EPCAM (cited Kastrinos et al. as reference 143).
Revised Table 4, Estimated Cumulative Breast and Ovarian Cancer Risks in Carriers of BRCA1 and BRCA2 Pathogenic Variants (cited Kuchenbaecker et al. as reference 126).
Revised Table 5, Contralateral Breast Cancer 10-Year Cumulative Risk Estimates for Carriers of BRCA1/BRCA2 Pathogenic Variants (cited Basu et al. as reference 154).
Added text about a study of 10- and 20-year risk estimates for contralateral breast cancer (CBC) in 506 BRCA1 carriers and 505 BRCA2carriers with a diagnosis of breast cancer.
Added text about an international, multicenter, prospective cohort study of 1,305 BRCA1 and 908 BRCA2 female carriers with a diagnosis of breast cancer that reported a cumulative risk of CBC 20 years after the initial breast cancer diagnosis of 40% for BRCA1 carriers and 26% for BRCA2 carriers.
Added text to state that HER2 positivity and young age alone in the absence of family history or a second primary cancer does not increase the likelihood of a pathogenic variant in BRCA1, BRCA2, or TP53 (cited Eccles et al. as reference 259).
Added text to state that a meta-analysis modeled the risk of breast cancer in carriers of ATM pathogenic variants to be 6.02% by age 50 years and 32.83% by age 80 years (cited Marabelli et al. as reference 59); given these risks, increased screening and other recommendations based on family history and age may be considered.
Added text about a 2015 Dutch case-control study that further evaluated 2,308 high-risk patients, including 706 women with known BRCA pathogenic variants, who were screened with mammogram and compared with those who had the addition of magnetic resonance imaging (cited Saadatmand et al. as reference 49).
Revised text to state that the timing of genetic testing and knowledge of BRCA pathogenic variant status may influence surgical decision making, prevent subsequent surgeries, and influence follow-up care.
Revised Table 13, Oral Contraceptive (OC) Use and Breast Cancer Risk in Carriers of BRCA1/BRCA2 Pathogenic Variants (cited Kotsopoulos et al. as reference 123).
Added text about a statistical Markov model using Monte Carlo simulation in which risk-reducing salpingectomy with delayed oophorectomy was a cost-effective strategy considering quality-adjusted life expectancy for women with pathogenic variants in BRCA1/BRCA2 (cited Kwon et al. as reference 223) and another study modeling ovarian cancer risk and effects of risk-reducing salpingo-oophorectomy (RRSO) and salpingectomy which found that the difference in estimated ovarian cancer risk is small when salpingectomy is performed on women of childbearing age and oophorectomy is performed 5 to 10 years later (cited Harmsen et al. as reference 224).
Added text about racial differences in provider discussion and patient uptake of genetic testing for variants in BRCA1/BRCA2 (cited McCarthy et al. as reference 33) and in uptake of RRSO, risk-reducing mastectomy, and risk management screening (cited Cragun et al. as reference 34).
Revised text to state that BRCA testing, when offered to women newly diagnosed with breast cancer, has been shown to influence surgical decision making in that carriers are more likely to opt for bilateral mastectomy compared with noncarriers (cited Rosenberg et al. as reference 225).
Added text about a study conducted from 2006 to 2014 in 11 U.S. academic and community centers of 897 women, aged 40 years and younger at breast cancer diagnosis, that found the rates of BRCA genetic testing have increased over time and that among women who tested positive for a pathogenic BRCA variant who stated that testing affected their surgery decisions, 86% underwent bilateral mastectomy compared with 51% of noncarriers.
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