Table A1.

Sensitivity Analysis on Outcomes of BC Incidence, Stage (% local), ER Expression (% ER positive), and OC Incidence by Age 70 Years in BRCA1/2 Mutation Carriers

Parameter	BC Incidence (%)			BC Stage (% local)			BC ER (% positive)			OC Incidence (%)
	Base	Lower	Upper	Base	Lower	Upper	Base	Lower	Upper	Base	Lower	Upper
BRCA1 mutation carriers
BC by 70 years, BRCA1	0.65	0.47	0.85	0.65	0.47	0.85	0.65	0.47	0.85	0.65	0.47	0.85
No S* or PM or PO	68	53	89	42	42	42	34	34	34	38	38	38
S*, no PM or PO	70	55	90	79	75	80	34	34	34	38	38	38
S* and PO, no PM†	52	39	77	77	74	78	34	34	34	10	10	10
S* and PO and PM†	25	19	38	81	80	82	37	37	37	10	10	10
OC by 70 years, BRCA1	0.39	0.39	0.46	0.39	0.39	0.46	0.39	0.39	0.46	0.39	0.39	0.46
No S* or PM or PO	68	68	68	42	42	42	34	34	34	38	38	46
S*, no PM or PO	70	70	70	79	79	79	34	34	34	38	38	46
S* and PO, no PM†	52	52	52	77	77	77	34	34	34	10	10	12
S* and PO and PM†	25	25	25	81	81	81	37	37	37	10	10	12
MRI sensitivity‡	0.85	0.50	0.90	0.85	0.50	0.90	0.85	0.50	0.90	0.85	0.50	0.90
No S* or PM or PO	68	68	68	42	42	42	34	34	34	38	38	38
S*, no PM or PO	70	69	71	79	59	82	34	34	34	38	38	38
S* and PO, no PM†	52	50	54	77	58	81	34	34	34	10	10	10
S* and PO and PM†	25	23	24	81	68	86	37	37	37	10	10	10
HR for BC after PO	0.5§	0.1	1	0.5§	0.1	1	0.5§	0.1	1	0.5§	0.1	1
No S* or PM or PO	68	68	68	42	42	42	34	34	34	38	38	38
S*, no PM or PO	70	70	70	79	79	79	34	34	34	38	38	38
S* and PO, no PM†	52	27	71	77	77	76	34	35	34	10	10	10
S* and PO and PM†	25	23	27	81	84	80	37	37	37	10	10	10
BRCA2 mutation carriers
BC by 70 years, BRCA2	0.45	0.4	0.85	0.45	0.4	0.85	0.45	0.4	0.85	0.45	0.4	0.85
No S* or PM or PO	50	45	86	47	47	47	78	78	78	11	11	11
S*, no PM or PO	53	48	88	80	77	83	78	78	78	11	11	11
S* and PO, no PM†	34	31	72	79	76	80	78	78	78	2	2	2
S* and PO and PM†	13	12	34	83	82	86	81	80	80	2	2	2
OC by 70 years, BRCA2	0.11	0.11	0.27	0.11	0.11	0.27	0.11	0.11	0.27	0.11	0.11	0.27
No S* or PM or PO	50	50	50	47	47	47	78	78	78	11	11	27
S*, no PM or PO	53	53	53	80	80	80	78	78	78	11	11	27
S* and PO, no PM†	34	34	34	79	79	79	78	78	78	2	2	6
S* and PO and PM†	13	13	13	83	83	83	81	81	81	2	2	6
MRI sensitivity‡	0.85	0.50	0.90	0.85	0.50	0.90	0.85	0.50	0.90	0.85	0.50	0.90
No S* or PM or PO	50	50	50	47	47	47	78	78	78	11	11	11
S*, no PM or PO	53	50	54	80	63	82	78	78	78	11	11	11
S* and PO, no PM†	34	32	36	79	62	81	78	78	78	2	2	2
S* and PO and PM†	13	13	13	83	71	86	81	80	80	2	2	2
HR for BC after PO	0.5§	0.1	1	0.5§	0.1	1	0.5§	0.1	1	0.5§	0.1	1
No S* or PM or PO	50	50	50	47	47	47	78	78	78	11	11	11
S*, no PM or PO	53	53	53	80	80	80	78	78	78	11	11	11
S* and PO, no PM†	34	15	52	79	79	78	78	79	78	2	2	2
S* and PO and PM†	13	12	15	83	86	80	81	81	80	2	2	2

NOTE. Parameters, varied from base case to lower and upper cases, are BC and OC risks by age 70 years owing to BRCA1/2 mutations (BC by 70 years, OC by 70 years), MRI sensitivity for BC detection, and HR for BC development after premenopausal PO; interventions evaluated are S, PM, and/or PO.

Abbreviations: BC, breast cancer; ER, estrogen receptor; HR, hazard ratio; MRI, magnetic resonance imaging; OC, ovarian cancer; PM, prophylactic mastectomy; PO, prophylactic oophorectomy; S, screening.

^*S consists of mammography and MRI annually, according to national practice guidelines^24,51; it is initiated at age 25 years and continued through age 69 years unless PM occurs, after which time breast S stops.

^†Prophylactic surgeries (PM and/or PO) are performed at age 40 years in these scenarios.

^‡MRI sensitivity varied in sensitivity analysis by adjusting the tumor size detection threshold between 0.3 cm (90% sensitivity) and 1.53 cm (50% sensitivity).

^§In the base case, the HR for BC is 0.50 after PO is performed between ages 40 and 50 years, as described in Table 1.