Table 1. Model Parameters.
| Parameter | Base case (lower-upper) | Distribution | Source |
|---|---|---|---|
| Mutation prevalence | |||
| Hereditary breast and ovarian cancer carrier prevalence (overall), % (±20%) | 0.495 (0.452-0.538) | Beta | Manickam et al7 and Dewey et al18 |
| Proportion: BRCA1 | 0.276 (0.221-0.332) | Dirichlet | Kurian et al19 |
| Proportion: BRCA2 | 0.290 (0.232-0.348) | Dirichlet | Kurian et al19 |
| Proportion: ATM | 0.121 (0.096-0.145) | Dirichlet | Kurian et al19 |
| Proportion: CHEK2 | 0.145 (0.116-0.174) | Dirichlet | Kurian et al19 |
| Proportion: MSH6 | 0.042 (0.034-0.051) | Dirichlet | Kurian et al19 |
| Proportion: PALB2 | 0.091 (0.073-0.109) | Dirichlet | Kurian et al19 |
| Proportion: RAD51C | 0.027 (0.022-0.032) | Dirichlet | Kurian et al19 |
| Proportion: TP53 | 0.008 (0.006-0.009) | Dirichlet | Kurian et al19 |
| Decision tree, % (±20%) | |||
| Carriers identified through family history–based testing | 0.174 (0.139-0.209) | Beta | Manchanda et al13 |
| Screening test | |||
| Sensitivity (±20%) | 0.991 (0.793-1.000) | Beta | Manchanda et al13 |
| Specificity (±20%) | 0.999 (0.799-1.000) | Beta | Toland et al20 |
| Proportion who avoid screening (±20%) | 0.050 (0.040-0.060) | Beta | Assumption |
| Proportion of known carriers who undergo magnetic resonance imaging (±20%) | 0.750 (0.600-0.900) | Beta | Assumption |
| Non-BRCA mutation breast cancer risk, OR (95% CI) | |||
| ATM | 2.97 (1.67-5.68) | Log normal | Lu et al21 |
| CHEK2 | 2.19 (1.40-3.56) | Log normal | Lu et al21 |
| MSH6 | 2.59 (1.35-5.44) | Log normal | Lu et al21 |
| PALB2 | 5.53 (2.24-17.65) | Log normal | Lu et al21 |
| Non-BRCA mutation ovarian cancer risk, OR (95% CI) | |||
| ATM | 2.85 (1.30-6.32) | Log normal | Lu et al21 |
| MSH6 | 4.16 (1.95-9.47) | Log normal | Lu et al21 |
| RAD51C | 18.38 (14.70-184.00) | Log normal | Lu et al21 |
| TP53 | 18.50 (2.56-808.10) | Log normal | Lu et al21 |
| Risk-reducing interventions | |||
| Breast cancer after mastectomy, HR (95% CI) | |||
| BRCA1 | 0 (No residual risk) | NA | Domchek et al2 |
| BRCA2 | 0 (No residual risk) | NA | Domchek et al2 |
| Non-BRCA | 0 (No residual risk) | NA | Assumption |
| Breast cancer after oophorectomy, HR (95% CI) | |||
| BRCA1 | 0.63 (0.41-0.96) | Log normal | Domchek et al2 |
| BRCA2 | 0.36 (0.16-0.82) | Log normal | Domchek et al2 |
| Non-BRCA | 0.36 (0.16-0.82) | Log normal | Assumption |
| Ovarian cancer after oophorectomy, HR (95% CI) | |||
| BRCA1 | 0.31 (0.12-0.82) | Log normal | Domchek et al2 |
| BRCA2 | 0 (No residual risk) | NA | Domchek et al2 |
| Non-BRCA | 0 (No residual risk) | NA | Assumption |
| Mortality, % (±20%) | |||
| Breast cancer mortality risk reduction: early stage | 0.943 (0.900-1.000) | Log normal | Evans et al22 |
| Breast cancer 5-y relative mortality | |||
| Aged <45 y | 0.119 (0.095-0.143) | Log normal | SEER program16 |
| Aged 45-54 y | 0.094 (0.075-0.113) | Log normal | SEER program16 |
| Aged 55-64 y | 0.099 (0.079-0.119) | Log normal | SEER program16 |
| Aged 65-74 y | 0.086 (0.069-0.103) | Log normal | SEER program16 |
| Aged ≥75 y | 0.129 (0.103-0.155) | Log normal | SEER program16 |
| Ovarian cancer 5-y relative mortality | |||
| Aged <45 y | 0.235 (0.188-0.282) | LogNormal | SEER program16 |
| Aged 45-54 y | 0.409 (0.327-0.491) | Log normal | SEER program16 |
| Aged 55-64 y | 0.505 (0.404-0.606) | Log normal | SEER program16 |
| Aged 65-74 y | 0.613 (0.490-0.736) | Log normal | SEER program16 |
| Aged ≥75 y | 0.791 (0.633-0.949) | Log normal | SEER program16 |
| Background mortality | US life tables | NA | CDC15 |
| Intervention uptake: non-BRCA mutations (±20%) | |||
| Rate ratio vs combined BRCA: mastectomy | 0.500 (0.400-0.600) | Log normal | Assumption |
| Rate ratio vs combined BRCA: oophorectomy | 0.500 (0.400-0.600) | Log normal | Assumption |
| Quality of life, % (±20%) | |||
| Utility: breast cancer | 0.663 (0.530-0.796) | Beta | Peasgood et al23 |
| Utility: ovarian cancer | 0.628 (0.502-0.754) | Beta | Manchanda et al13 |
| Utility: after breast cancer | 0.810 (0.648-0.972) | Beta | Manchanda et al13 |
| Utility: after ovarian cancer | 0.720 (0.576-0.864) | Beta | Havrilesky et al24 |
| Disutility (1 y): mastectomy | 0.030 (0.024-0.036) | Beta | Li et al25 |
| Disutility (1 y): oophorectomy | 0.030 (0.024-0.036) | Beta | Li et al25 |
| Disutility (1 y): knowledge of variant | 0.050 (0.040-0.060) | Beta | Li et al25 |
| Disutility: screening harm to noncarriers (scenario analysis) | 0.030 (0.029-0.032) | Beta | Mandelblatt et al26 |
| Risk-reducing intervention costs, mean (±20%), $ | |||
| Mastectomy | 22 110 (17 688-26 532) | Normal | Sun et al27 |
| Oophorectomy | 8476 (6781-10 171) | Normal | Sun et al27 |
| Mammography | 228 (182-274) | Normal | Sun et al27 |
| Intense screening (magnetic resonance imaging) | 1403 (1122-1683) | Normal | Sun et al27 |
| Screening assay | 200 (160-240) | Normal | Color Genomics28 |
| Confirmation | 200 (160-240) | Normal | Color Genomics28 |
| Cancer treatment costs, mean (±20%), $ | |||
| Aged <65 y | |||
| Breast cancer—initial | 83 633 (66 906-100 360) | Normal | Sun et al27 |
| Breast cancer—continuing | 8048 (6438-9658) | Normal | Sun et al27 |
| Breast cancer—last year | 68 022 (54 418-81 626) | Normal | Sun et al27 |
| Ovarian cancer—initial | 133 121 (106 497-159 745) | Normal | Sun et al27 |
| Ovarian cancer—continuing | 14 635 (11 708-17 562) | Normal | Sun et al27 |
| Ovarian cancer—last year | 93 005 (74 404-111 606) | Normal | Sun et al27 |
| Aged ≥65 y | |||
| Breast cancer—initial | 83 633 (66 906-100 360) | Normal | Sun et al27 |
| Breast cancer—continuing | 8048 (6438-9658) | Normal | Sun et al27 |
| Breast cancer—last year | 68 022 (54 418-81 626) | Normal | Sun et al27 |
| Ovarian cancer—initial | 133 121 (106 497-159 745) | Normal | Sun et al27 |
| Ovarian cancer—continuing | 14 635 (11 708-17 562) | Normal | Sun et al27 |
| Ovarian cancer—last year | 93 005 (74 404-111 606) | Normal | Sun et al27 |
| Cascade testing parameters, % (±20%) | |||
| Proportion identified carriers who inform family | 0.70 (0.56-0.84) | Beta | Roberts et al29 and Elrick et al30 |
| Proportion of family members ever tested | 0.20 (0.16-0.24) | Beta | Roberts et al29 and Elrick et al30 |
Abbreviations: CDC, Centers for Disease Control and Prevention; HR, hazard ratio; NA, not applicable; OR, odds ratio; SEER, Surveillance, Epidemiology, and End Results.