Table 5.

Model average benefits, harms, and benefit to harm ratios comparison of risk-based screening based on BC FH, PRS, and FH combined with polygenic risk for both the primary analysis and the sensitivity analysis

Risk-based screening outcomes	Screening based on	Screens, No.	LYG	BC deaths averted	Over diagnoses	False positives	LYG/screens	LYG/overdiagnoses/	BC deaths averted/false positives
Main analyses
Risk based	FH (strategies in Table 3)	11 840	125	6.9	14.9	1000	0.0105	8.35	0.0069
Risk based	Polygenic risk (strategies in Table 4)	12 990	141	7.4	16.0	1156	0.0109	8.85	0.0064
Risk based	FH and polygenic riska	13 089	154	7.9	16.6	1169	0.0117	9.23	0.0067
Sensitivity analysis
Risk based (constrained)b	Polygenic risk (strategies in Table 6)	10 856	135	7.1	14.0	946	0.0124	9.64	0.0075

^aResults per 1000 women screened. The screening strategies and associated harms and benefits are listed in Supplementary Table 6 (available online). BC = breast cancer; FH = family history; LYG = life-years gained; PRS = polygenic risk score.

^bThe constrained risk-based screening approach represents a scenario where the number of screens of the United States Preventive Services Task Force screening guidelines (top row) was not increased but rather was redistributed across the population based on the PRSs (strategies given in Table 6). The number of screens do not exactly match because all women in each risk group were assigned to one of the screening strategies listed in the Methods section.