Table 2.

Association of protein-truncating variants in nine breast cancer genes and of pathogenic/likely pathogenic rare missense variants in BRCA1, BRCA2, and TP53 with breast cancer-specific survival

Gene	Unadjusted analyses		Adjusted analysesa		No. of women		No. of BC deaths
PTVs (unless indicated otherwise)	HR (95% CI)	p	HR (95% CI)	p	Non-carriers	Carriers	Non-carriers	Carriers
ATM	1.24 (0.85–1.83)	2.7E−01	1.07 (0.73–1.57)	7.3E−01	34,151	250	3,421	28
BARD1	1.14 (0.46–2.79)	7.8E−01	0.90 (0.38–2.15)	8.2E−01	34,347	54	3,444	5
BRCA1b	1.22 (0.89–1.66)	2.2E−01	0.90 (0.66–1.22)	4.9E−01	34,037	364	3,406	43
BRCA2b	1.54 (1.21–1.95)∗	5.0E−04∗	1.20 (0.95–1.52)	1.2E−01	33,914	487	3,372	77
CHEK2	1.47 (1.19–1.82)∗	3.7E−04∗	1.39 (1.13–1.72)∗	2.2E−03∗	33,702	699	3,349	100
c.1100delC	1.46 (1.15–1.85)∗	1.6E−03∗	1.43 (1.13–1.81)∗	3.0E−03∗	33,702	561	3,349	81
Other	1.51 (0.93–2.44)	9.6E−02	1.26 (0.79–2.02)	3.4E−01	33,702	138	3,349	19
PALB2	1.65 (1.15–2.36)∗	6.7E−03∗	1.39 (0.98–1.98)	6.8E−02	34,177	224	3,414	35
RAD51C	0.77 (0.26–2.28)	6.4E−01	0.79 (0.27–2.38)	6.8E−01	34,361	40	3,446	3
RAD51D	1.48 (0.63–3.46)	3.7E−01	0.95 (0.43–2.12)	9.1E−01	34,370	31	3,443	6
TP53b	2.52 (1.13–5.60)∗	2.4E−02∗	2.08 (0.95–4.57)	6.8E−02	34,354	47	3,441	8

Abbreviations: No., number; BC, breast cancer; PTVs, protein-truncating variants; HR, hazard ratio; CI, confidence interval; p, p value. Analyses included women from 34 studies listed in Table S1, excluding women who developed a CBC before study entry. Statistically significant associations (p < 5E−02) are denoted with an asterisk.

^aWe performed adjusted analyses by including age at diagnosis, nodal status, size category, grade, estrogen receptor (ER) status ERB-B2 receptor tyrosine kinase 2 (ERBB2) status of the first breast cancer, (neo)adjuvant chemotherapy, endocrine therapy, and trastuzumab as covariates in the Cox regression model.

^bCombined PTVs and pathogenic/likely pathogenic rare missense variants as defined in Dorling et al. (2021).¹⁸