Table 1. Association of PTVs With BC Risk, as Stratified by Mode of Detection.
| PTVs | BC vs controls, adjusted by age at baseline (n = 9752)a | SDC vs controls, adjusted by age at baseline (n = 8523)b | IC vs controls, adjusted by age at baseline (n = 6860)c | ||||||
|---|---|---|---|---|---|---|---|---|---|
| No. | BC vs controls, OR (95% CI) | No. | SDC vs controls, OR (95% CI) | No. | IC vs controls, OR (95% CI) | ||||
| Controls | BC | Controls | SDC | Controls | IC | ||||
| Full panel (34 PTVs) | |||||||||
| Noncarriers | 5422 | 3819 | 1 [Reference] | 5422 | 2686 | 1 [Reference] | 5422 | 1133 | 1 [Reference] |
| Carriers | 209 | 302 | 2.04 (1.70-2.44) | 209 | 206 | 1.99 (1.63-2.42) | 209 | 96 | 2.17 (1.69-2.79) |
| Panel excluding 5 major genes | |||||||||
| Noncarriers | 5422 | 3819 | 1 [Reference] | 5422 | 2686 | 1 [Reference] | 5422 | 1133 | 1 [Reference] |
| Carriers | 120 | 134 | 1.58 (1.23–2.03) | 120 | 101 | 1.70 (1.30-2.22) | 120 | 33 | 1.31 (0.88-1.93) |
| 5 Major genes for BC | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 89 | 168 | 2.62 (2.02-3.40) | 89 | 105 | 2.34 (1.76-3.11) | 89 | 63 | 3.30 (2.38-4.59) |
| BRCA1/2 + PALB2 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5422 | 2787 | 1 [Reference] | 5422 | 1166 | 1 [Reference] |
| Carriers | 18 | 68 | 5.24 (3.11-8.83) | 18 | 37 | 4.07 (2.31-7.17) | 18 | 31 | 7.99 (4.45-14.35) |
| ATM + CHEK2 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5422 | 2787 | 1 [Reference] | 5422 | 1166 | 1 [Reference] |
| Carriers | 71 | 101 | 1.98 (1.46-2.69) | 71 | 68 | 1.90 (1.36-2.66) | 71 | 33 | 2.17 (1.43-3.30) |
| BRCA1 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 3 | 12 | 5.59 (1.58-19.83) | 3 | 6 | 3.97 (0.99-15.89) | 3 | 6 | 9.54 (2.38-38.24) |
| BRCA2 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 10 | 42 | 5.81 (2.91-11.60) | 10 | 23 | 4.56 (2.16-9.59) | 10 | 19 | 8.74 (4.05-18.85) |
| PALB2 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 5 | 14 | 3.89 (1.40-10.80) | 5 | 8 | 3.17 (1.04-9.70) | 5 | 6 | 5.59 (1.70-18.36) |
| ATM | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 12 | 27 | 3.15 (1.59-6.22) | 12 | 19 | 3.14 (1.52-6.48) | 12 | 8 | 3.18 (1.29-7.79) |
| CHEK2 | |||||||||
| Noncarriers | 5542 | 3953 | 1 [Reference] | 5542 | 2787 | 1 [Reference] | 5542 | 1166 | 1 [Reference] |
| Carriers | 59 | 74 | 1.74 (1.23-2.46) | 59 | 49 | 1.65 (1.12-2.41) | 59 | 25 | 1.97 (1.23-3.16) |
Abbreviations: BC, breast cancer; IC, interval breast cancer; OR, odds ratio; PTVs, protein-truncating variants; SDC, screen-detected breast cancer.
We included patients with BC with a diagnosis of SDC (n = 2892) and IC (n = 1229) and compared them with healthy controls (n = 5631). PTVs are grouped into different panels (based on the previously reported association with BC), followed by individualized analysis for the 5 major genes for BC. The left column includes all patients with BC attending to mammographic screening (SDC and IC) compared with controls.
The middle column includes patients with a diagnosis of SDC compared with controls.
The right column includes patients with a diagnosis of IC compared with controls. All models were adjusted by age at baseline.