Assumptions Risk level Risk level
Moderate High
Number of women screened100,000100,000
Prevalence of clinically significant BRCA mutations (%)
BRCA1 0.82(0.53 – 1.28)6.42(1.13 – 29.09)
BRCA2 1.13(0.88 – 1.44)1.1(0.61 –1.98)
Penetrance of mutation to age 40/50 (%)
Breast cancer (to age 40 years)
BRCA1 5.03(1.85,12.97)6.88(1.92–21.78)
BRCA2 1.23(0.40–3.75)9.1(4.11–18.94)
Ovarian cancer (to age 50 years)#
BRCA1 14.16(9.17–21.23)no data
BRCA2 1.79(0.88, 3.58)no data
Penetrance of mutation to age 75 (%)
Breast cancer
BRCA1 38.83(27.26–51.80)44.14(11.47–82.82)
BRCA2 24.89(13.11–42.14)24.17(17.20–32.84)
Ovarian cancer#
BRCA1 31.49(21.91–42.96)21.67(4.84–60.07)
BRCA2 11.72(8.16 –16.56)44.57(28.06–62.37)
Risk reduction of SERMs to prevent all types of breast cancer, trials with mutation status unknown (RR=0.62; 0.46–0.83)0.38(0.17 – 0.54)0.38(0.17 – 0.54)
Risk of thromboembolic events from SERMs (% per year)0.096(0.036–0.156)0.096(0.036–0.156)
Risk of endometrial cancer from SERMs (% per year)0.036(0.00177 – 0.0709)0.036(0.00177 – 0.0709)
Proportion of candidates choosing SERMs (%) (not known)uniform(5,50)uniform(5,50)
Risk reduction of mastectomy to prevent breast cancer if BRCA mutation (RR=0; 0–0.36)0.91(0.64–1.00)0.91(0.64–1.00)
Risk of complications from mastectomy and reconstruction (% overall) (based on one study; range not known)2121
Proportion of candidates choosing mastectomy (%) (not known)uniform(5,20)uniform(5,20)
Risk reduction of oophorectomy to prevent breast cancer if BRCA mutation (RR=0.32; 0.08–1.20)0.68(0.01–0.92)0.68(0.01–0.92)
Risk of complications from oophorectomy (% overall) (based on one study; range not known)55
Proportion of candidates choosing oophorectomy (%) (not known)uniform(25,75)uniform(25,75)
Risk reduction of oophorectomy to prevent ovarian cancer in BRCA mutation ((RR-0.15; 0.02–2.31)0.85 (0.01–0.99)0.85 (0.01–0.99)
Risk of complications from oophorectomy (% overall) (based on one study; range not known)55
Proportion of candidates choosing oophorectomy (%) (not known)uniform(25,75)uniform(25,75)
Risk level Risk level
Outcomes-benefits to age 40 Moderate High
Number of breast cancer cases expected among candidates if not undergoing treatment58(26–126)467(158,1707)
Number of breast cancer cases prevented among candidates taking SERMs (using overall risk reduction of 0.38)5.4(0.93–18.3)43(6.3–219)
NNS to prevent 1 case of breast cancer using SERMs18677(5466–108044)2344(456–15930)
NNT with SERMs to prevent 1 case of breast cancer92(37–273)44(11–164)
Number of breast cancer cases prevented among candidates undergoing mastectomy6.3(1.9–17.3)50(12–217)
NNS to prevent 1 case of breast cancer using mastectomy15988(5771–51294)1987(460–8076)
NNT with mastectomy to prevent 1 case of breast cancer37.1(16.7–85.4)17.8(4.8–54)
Number of breast cancer cases prevented among candidates if undergoing oophorectomy16.7(0.27–51.6)134(2.1 – 633)
NNS to prevent 1 case of breast cancer using oophorectomy5924(1940–371335)747(158–46855)
NNT with oophorectomy to prevent 1 case of breast cancer54(21.2 – 3463)27(6.3–1693)
Number of ovarian cancer cases expected among candidates if not undergoing treatment138(94–198)No data
Number of ovarian cancer cases prevented among candidates undergoing oophorectomy51(0.62–107)No data
NNS to prevent 1 case of ovarian cancer using oophorectomy1968(934–161826)No data
NNT with oophorectomy to prevent 1 case of ovarian cancer 17.7(11.1–1476)No data
Risk level Risk level
Outcomes-benefits to age 75 Moderate High
Number of breast cancer cases expected among candidates if not undergoing treatment604(433–820)3465(1361 –5955)
Number of breast cancer cases prevented among candidates taking SERMs (using overall risk reduction of 0.38)58(11–143)306(51–971)
NNS to prevent 1 case of breast cancer using SERMs1739(697–8814)327(103 – 1945)
NNT with SERMs to prevent 1 case of breast cancer8.6(5.3–20.6)6.0(2.9–19.6)
Number of breast cancer cases prevented among candidates undergoing mastectomy67(26–128)360(105–894)
NNS to prevent 1 case of breast cancer using mastectomy1497(783–3801)278(112–952)
NNT with mastectomy to prevent 1 case of breast cancer3.5(2.5–5.6)2.4(1.3–6.3)
Number of breast cancer cases prevented among candidates if undergoing oophorectomy181(2.9–395)972(16–2710)
NNS to prevent 1 case of breast cancer using oophorectomy554(253–34512)103(37–6395)
NNT with oophorectomy to prevent 1 case of breast cancer4.9(3.0–327)3.6(1.6–223)
Number of ovarian cancer cases expected among candidates if not undergoing treatment393(302–499)1888(782–4357))
Number of ovarian cancer cases prevented among candidates undergoing oophorectomy146(1.8–286)668(7.9 – 2110)
NNS to prevent 1 case of ovarian cancer using oophorectomy687(350–56591)150(47 – 12658)
NNT with oophorectomy to prevent 1 case of ovarian cancer6.1(4.3–512)5.3(2.0 – 447)
Risk level Risk level
Outcomes-adverse effects Moderate High
Number of women taking SERMs544(119–1044)1893(292–9885)
Number of cases of thrombotic events due to SERMs0.52(0.088–1.24)2.59(0.22–10.1)
NNT with SERMs to cause one thrombotic event1042(641–2719)1042(641–2719)
Number of cases of endometrial cancer due to SERMs0.20(0.0068–0.54)0.98(0.019–4.14)
NNT with SERMs to cause one case of endometrial cancer2686(1228–15726)2686(1228–15726)
Number of women undergoing mastectomy247(102–424)897(201–4176)
Number of women with complications from52.0(21.4–89.0)188(42–877)
NNT with mastectomy to cause one complication55
Number of women undergoing oophorectomy990(490–1601)3651(901–16246)
Number of women with complications from oophorectomy49.5(24.5–80.0)183(45–812)
NNT oophorectomy to cause one complication2020

NNS, number needed to screen; NNT, number needed to treat; SERMs, selective estrogen receptor modulators.

From: Appendix S. Sensitivity Analyses

Cover of Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility
Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility [Internet].
Evidence Syntheses, No. 37.
Nelson HD, Huffman LH, Fu R, et al.

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