Added text about a study of 80,309 monozygotic twins and 123,382 dizygotic twins that reported a heritability estimate for breast cancer of 31% (cited Mucci et al. as reference 11); however, a high rate of discordance even between monozygotic twins suggests that environmental factors also have a role in modifying breast cancer risk.
Added text about a retrospective cohort study of 691 patients with BRCA1/2-associated breast cancer who were followed up for a median of 8.6 years; no association between receiving adjuvant radiation therapy and increased risk of contralateral breast cancer was seen in the entire cohort, including the subset of patients younger than 40 years at primary breast cancer diagnosis (cited Drooger et al. as reference 39).
Added text to state that non-Lynch syndrome (LS) genes may also contribute to endometrial cancer risk; in an unselected endometrial cancer cohort undergoing multigene panel testing, approximately 3% of patients tested positive for a germline pathogenic variant in non-LS genes (cited Ring et al. as reference 88). Also added that patients with pathogenic variants in non-LS genes were more likely to have serous tumor histology, and carriers of BRCA1 pathogenic variants seemed to be a higher risk of serous and serous-like endometrial cancer (cited Shu et al. as reference 89).
Added text to state that in an unselected population of endometrial cancer patients, the prevalence of LS variants was 5.8%; the prevalence of pathogenic variants in other actionable genes was 3.4% (cited Ring et al. as reference 5).
Added text about studies that have suggested that BRCA pathogenic variants may be associated with genetic anticipation (cited Guindalini et al. and Agranat et al. as references 130 and 131, respectively).
Added text to state that the evidence for the effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer has evolved; early small studies suggested a protective benefit. Initial retrospective studies supported breast cancer and ovarian cancer risk reduction after RRSO in BRCA pathogenic variant–positive women. Also added that an international, multi-institutional study of 3,722 BRCA1 and BRCA2 carriers showed that oophorectomy performed before age 50 years was beneficial for preventing breast cancer in BRCA2 carriers but not in BRCA1 carriers (cited 2017 Kotsopoulos et al. as reference 87).
Added text to state that a case-control study of 432 matched pairs of postmenopausal women with a BRCA1 pathogenic variant who had a personal history of cancer were compared with unaffected BRCA1 carriers. The use of hormone-replacement therapy was not associated with an increased risk of developing breast cancer (cited 2016 Kotsopoulos et al. as reference 134).
Added text about a qualitative study of 54 Latina women at risk of hereditary breast cancer that showed that knowledge about BRCA1/2 genetic counseling was low, although the women were interested in learning more about counseling to gain risk information for family members (cited Sussner et al. as reference 28).
Added text to state that a study of mother-daughter pairs from families with a BRCA1/2 pathogenic variant in which the daughters were aged 11 to 19 years found that higher breast cancer–specific distress in daughters was associated with perceived risk and maternal distress; this age group had higher self-esteem than did their peers without a family history of breast cancer (cited Bradbury et al. as reference 153).
Added text to state that a multisite randomized trial of 150 unaffected women withBRCA1/BRCA2 pathogenic variants assessed the effect of a decision aid on breast cancer risk management decisions and psychosocial outcomes. At 6-month and 12-month follow-up, women randomly assigned to the decision aid had lower levels of cancer-related distress than did the control group. Decisional conflict scores were relatively low at baseline and declined over time in both groups (cited 2016 Metcalfe et al. as reference 196).
Added text about a retrospective survey of 137 BRCA carriers that examined the psychosocial impact of preserving the nipple-areolar complex (NAC) in women with bilateral risk-reducing mastectomy (RRM) (cited 2015 Metcalfe et al. as reference 243) and found that body image and sexual well-being differed significantly based on the type of RRM the women underwent; no differences in cancer-related distress, anxiety, depression, or risk perceptions were observed between the two groups. Also added that oncologic outcomes of nipple-sparing mastectomy in BRCA carriers have not been inferior to RRM without NAC preservation (cited Yao et al. as reference 244).
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