Table 1.
Characteristics of the participants.
| BRCA1 heterozygotes | BRCA2 heterozygotes | ||||
|---|---|---|---|---|---|
| UBC, n (%) | CBC, n (%) | UBC, n (%) | CBC, n (%) | ||
| N | 5,189 | 1,402 | 3,561 | 647 | |
| Genotyping array | iCOGS | 895 (17) | 200 (14) | 383 (11) | 80 (12) |
| OncoArray | 4,294 (83) | 1,202 (86) | 3,178 (89) | 567 (88) | |
| Birth cohort | <1920 | 25 (0.5) | 8 (0.6) | 23 (0.6) | 9 (1) |
| 1920–1929 | 143 (3) | 46 (3) | 121 (3) | 30 (5) | |
| 1930–1939 | 392 (8) | 130 (9) | 341 (10) | 99 (15) | |
| 1940–1949 | 1,060 (20) | 386 (28) | 793 (22) | 172 (27) | |
| 1950–1959 | 1,540 (30) | 452 (32) | 1,104 (31) | 202 (31) | |
| 1960–1969 | 1,354 (26) | 298 (21) | 822 (23) | 115 (18) | |
| ≥1970 | 675 (13) | 82 (6) | 357 (10) | 20 (3) | |
| Variant classa | I | 3,354 (65) | 904 (64) | 3,207 (90) | 570 (88) |
| II | 1,345 (26) | 374 (27) | 125 (4) | 25 (4) | |
| III | 490 (9) | 124 (9) | 229 (6) | 52 (8) | |
| BRRM | 160 (3) | 0 | 101 (3) | 0 | |
| Deceased | N | 44 (0.8) | 12 (0.9) | 19 (0.5) | 2 (0.3) |
| Family historyb | No BC | 583 (11) | 175 (12) | 289 (8) | 78 (12) |
| 1 BC | 906 (17) | 270 (19) | 760 (21) | 127 (20) | |
| ≥ 2 BC | 1,250 (24) | 363 (26) | 1,120 (31) | 210 (32) | |
| Unknown | 2,450 (47) | 594 (42) | 1,392 (39) | 232 (36) | |
| Characteristics of first BC | |||||
| Age at diagnosis | Mean | 41.8 | 38.5 | 44.5 | 41.8 |
| Range | 19–82 | 19–68 | 18–85 | 21–75 | |
| ER status | Positive | 570 (11) | 92 (7) | 1,302 (37) | 182 (28) |
| Negative | 1,738 (33) | 402 (29) | 424 (12) | 61 (9) | |
| Unknown | 2,881 (56) | 908 (65) | 1,835 (52) | 404 (62) | |
| Node status | Positive | 797 (15) | 182 (13) | 781 (22) | 119 (18) |
| Negative | 1,544 (30) | 441 (31) | 877 (25) | 151 (23) | |
| Unknown | 2,848 (55) | 779 56) | 1,903 (53) | 377 (58) | |
| Tumor sizec | T1 | 1,261 (24) | 314 (22) | 842 (24) | 136 (21) |
| T2 | 771 (15) | 211 (15) | 553 (16) | 87 (13) | |
| T3 | 67 (13) | 12 (0.9) | 78 (2) | 8 (1) | |
| T4 | 16 (0.5) | 2 (0.1) | 22 (0.6) | 2 (0.3) | |
| Unknown | 3,074 (59) | 863 (62) | 2,066 (58) | 414 (64) | |
| Chemotherapyd | Yes | 1,099 (21) | 236 (17) | 821 (23) | 123 (19) |
| No | 576 (11) | 212 (15) | 503 (14) | 129 (20) | |
| Unknown | 3,514 (68) | 954 (68) | 2,237 (63) | 395 (61) | |
| Adjuvant hormone therapy | Yes | 493 (10) | 125 (9) | 795 (22) | 111 (17) |
| No | 1,103 (21) | 288 (21) | 474 (13) | 135 (21) | |
| Unknown | 3,593 (69) | 989 (71) | 2,292 (64) | 401 (62) | |
| Adjuvant trastuzumab therapy | Yes | 11 (0.2) | 1 (0.1) | 20 (0.6) | 0 (0) |
| No | 1,161 (22) | 351 (25) | 983 (28) | 218 (34) | |
| Unknown | 4,017 (77) | 1,050 (75) | 2,558 (72) | 429 (66) | |
| Radiotherapy | Yes | 1,090 (21) | 277 (20) | 797 (22) | 158 (24) |
| No | 535 (10) | 141 (10) | 420 (12) | 84 (13) | |
| Unknown | 3,564 (69) | 984 (70) | 2,344 (66) | 405 (63) | |
| Characteristics of CBC | |||||
| Age at diagnosis | Mean | – | 47.3 | – | 51.24 |
| Range | – | 26–80.5 | – | 23.8–86 | |
| Invasiveness | Invasive | – | 1,267 (90) | – | 545 (84) |
| Noninvasive | – | 135 (10) | – | 102 (16) | |
| ER status | Positive | – | 101 (7) | – | 197 (30) |
| Negative | – | 446 (32) | – | 50 (8) | |
| Unknown | – | 855 (61) | – | 400 (62) | |
| PRS313 | |||||
| Standardized PRS313 mean (SD) | Overall BC | 0.08 (1.01) | 0.13 (1.01) | 0.09 (1.02) | 0.27 (1.04) |
| ER-positive BC | 0.07 (1.01) | 0.09 (1.01) | 0.08 (1.01) | 0.27 (1.03) | |
| ER-negative BC | 0.09 (1.00) | 0.23 (0.99) | 0.07 (1.02) | 0.23 (1.07) | |
BC breast cancer, BRRM bilateral risk-reducing mastectomy, CBC contralateral breast cancer, ER status estrogen receptor status of the tumor, PRS polygenic risk score, SD standard deviation, UBC unilateral breast cancer.
aVariant class: I = unstable or no protein, II = stable mutant protein, III = consequence unknown.
bFamily history was defined as the number of first- or second-degree relatives affected with BC, ranging from 0 to ≥2.
cTumor size: T1 = ≤ 2 cm (≤0.79 inches), T2 = > 2cm-5cm (>0.79–1.97 inches), T3 = > 5 cm (>1.97 inches), T4 = any size, with direct extension to the chest wall or skin.
dIncluding neoadjuvant and adjuvant chemotherapy.