Application of original MSS1, current MSS2 and new pathology-adjusted Manchester score MSS3 to 4113 index cases from unrelated families affected by breast/ovarian cancer
Manchester score | <15 | 15–19 | 20–24 | 25–29 | 30+ | Total mutation | Total tested | % | BRCA1 | % | BRCA2 | % | ||||||||||
BRCA1/2 | Number tested | % | BRCA1/2 | Number tested | % | BRCA1/2 | Number tested | % | BRCA1/2 | Number tested | % | BRCA1/2 | Number tested | % | ||||||||
ER− HER2+ original MSS1 | 0 | 19 | 0.0 | 0 | 10 | 0.0 | 2 | 10 | 20.0 | 2 | 6 | 33.3 | 2 | 3 | 66.7 | 6 | 48 | 12.5 | 4 | 8.3 | 2 | 4.2 |
ER− HER2+ current MSS2 | 0 | 28 | 0.0 | 2 | 9 | 22.2 | 1 | 6 | 16.7 | 2 | 4 | 50.0 | 1 | 1 | 100.0 | 6 | 48 | 12.5 | 4 | 8.3 | 2 | 4.2 |
ER− HER2+ new MSS3 | 0 | 26 | 0.0 | 2 | 11 | 18.2 | 1 | 6 | 16.7 | 2 | 4 | 50.0 | 1 | 1 | 100.0 | 6 | 48 | 12.5 | 4 | 8.3 | 2 | 4.2 |
ER+ HER2+ MSS1 | 1 | 48 | 2.1 | 1 | 28 | 3.6 | 3 | 28 | 10.7 | 1 | 17 | 5.9 | 0 | 9 | 0.0 | 6 | 130 | 4.6 | 1 | 0.8 | 5 | 3.8 |
ER+ HER2+ MSS2 | 2 | 72 | 2.8 | 3 | 32 | 9.4 | 1 | 16 | 6.3 | 0 | 5 | 0.0 | 0 | 5 | 0.0 | 6 | 130 | 4.6 | 1 | 0.8 | 5 | 3.8 |
ER+ HER2+ MSS3 | 2 | 80 | 2.5 | 3 | 28 | 10.7 | 1 | 13 | 7.7 | 0 | 8 | 0.0 | 0 | 1 | 0.0 | 6 | 130 | 4.6 | 1 | 0.8 | 5 | 3.8 |
TNT MSS1 | 32 | 250 | 12.8 | 33 | 89 | 37.1 | 30 | 66 | 45.5 | 23 | 31 | 74.2 | 41 | 47 | 87.2 | 159 | 483 | 32.9 | 125 | 25.9 | 34 | 7.0 |
TNT MSS2 | 11 | 137 | 8.0 | 24 | 119 | 20.2 | 37 | 101 | 36.6 | 30 | 57 | 52.6 | 57 | 69 | 82.6 | 159 | 483 | 32.9 | 125 | 25.9 | 34 | 7.0 |
TNT MSS3 | 7 | 112 | 6.3 | 13 | 86 | 15.1 | 39 | 126 | 31.0 | 29 | 69 | 42.0 | 71 | 90 | 78.9 | 159 | 483 | 32.9 | 125 | 25.9 | 34 | 7.0 |
TNT<30 | 0 | 0 | 0.0 | 4 | 24 | 16.7 | 2 | 4 | 50.0 | 3 | 8 | 37.5 | 13 | 14 | 92.9 | 22 | 50 | 44.0 | 19 | 38.0 | 3 | 6.0 |
TNT 30–39 | 3 | 75 | 4.0 | 3 | 20 | 15.0 | 14 | 46 | 30.4 | 10 | 20 | 50.0 | 30 | 38 | 78.9 | 60 | 199 | 30.2 | 53 | 26.6 | 7 | 3.5 |
TNT 40–49 | 3 | 28 | 10.7 | 5 | 27 | 18.5 | 15 | 39 | 38.5 | 9 | 23 | 39.1 | 22 | 27 | 81.5 | 54 | 144 | 37.5 | 40 | 27.8 | 14 | 9.7 |
TNT 50+ | 1 | 9 | 11.1 | 2 | 15 | 13.3 | 8 | 36 | 22.2 | 6 | 19 | 31.6 | 6 | 11 | 54.5 | 23 | 90 | 25.6 | 13 | 14.4 | 10 | 11.1 |
HGSOC MSS2+ | 15 | 140 | 10.7 | 7 | 43 | 16.3 | 10 | 24 | 41.7 | 3 | 8 | 37.5 | 3 | 5 | 60.0 | 38 | 220 | 17.3 | 29 | 13.2 | 9 | 4.1 |
HGSOC MSS3+ | 0 | 24 | 0.0 | 20 | 155 | 12.9 | 5 | 20 | 25.0 | 10 | 17 | 58.8 | 3 | 4 | 75.0 | 38 | 220 | 17.3 | 29 | 13.2 | 9 | 4.1 |
All ovarian case MSS3 | 3 | 96 | 3 | 30 | 255 | 11.8 | 31 | 114 | 27.2 | 39 | 110 | 35.5 | 87 | 139 | 62.6 | 190 | 714 | 26.6 | 123 | 17.2 | 67 | 9.4 |
All ovarian MSS1* | 18 | 206 | 8.7 | 34 | 253 | 13.4 | 65 | 266 | 24.4 | 66 | 234 | 28.2 | 182 | 308 | 59.1 | 365 | 1267 | 28.8 | 227 | 17.9 | 138 | 10.9 |
Ovarian MSS2* | 18 | 248 | 7.3 | 23 | 244 | 9.4 | 69 | 266 | 25.9 | 68 | 205 | 33.2 | 187 | 304 | 61.5 | 365 | 1267 | 28.8 | 227 | 17.9 | 138 | 10.9 |
All ovarian* MSS3 | 3 | 134 | 2.2 | 37 | 349 | 10.6 | 56 | 247 | 22.7 | 78 | 224 | 34.8 | 191 | 313 | 61.0 | 365 | 1267 | 28.8 | 227 | 17.9 | 138 | 10.9 |
Ovarian path adjusted only confirmed ovarian cancer | 9 | 214 | 4.2 | 38 | 357 | 10.6 | 66 | 237 | 27.8 | 83 | 209 | 39.7 | 169 | 250 | 67.6 | 365 | 1267 | 28.8 | 227 | 17.9 | 138 | 10.9 |
Breast-only MSS1 | 65 | 1372 | 4.7 | 74 | 700 | 10.4 | 89 | 441 | 20.2 | 55 | 185 | 29.7 | 70 | 151 | 46.4 | 352 | 2849 | 12.4 | 157 | 5.5 | 195 | 6.8 |
Breast-only MSS2 | 49 | 1316 | 3.7 | 74 | 789 | 9.4 | 89 | 396 | 22.5 | 58 | 191 | 30.4 | 83 | 157 | 52.9 | 353 | 2849 | 12.4 | 157 | 5.5 | 195 | 6.8 |
Breast-only MSS3 | 43 | 1292 | 3.3 | 66 | 757 | 8.7 | 95 | 434 | 21.9 | 56 | 194 | 28.9 | 93 | 172 | 54.1 | 353 | 2849 | 12.4 | 157 | 5.5 | 195 | 6.8 |
Breast MSS3 with path avail | 33 | 920 | 3.6 | 63 | 625 | 10.1 | 103 | 411 | 25.1 | 84 | 243 | 34.6 | 180 | 287 | 62.7 | 463 | 2486 | 18.6 | 131 | 5.3 | 144 | 5.8 |
Breast/ovarian path avail MSS1 | 73 | 1165 | 6.3 | 92 | 709 | 13.0 | 126 | 525 | 24.0 | 103 | 325 | 31.7 | 207 | 361 | 57.3 | 601 | 3085 | 19.5 | 335 | 10.9 | 266 | 8.6 |
Breast/ovarian path avail MSS2 | 56 | 1130 | 5.0 | 82 | 789 | 10.4 | 128 | 486 | 26.3 | 109 | 312 | 34.9 | 226 | 368 | 61.4 | 601 | 3085 | 19.5 | 335 | 10.9 | 266 | 8.6 |
Breast/ovarian path avail MSS3 | 35 | 995 | 3.5 | 88 | 859 | 10.2 | 124 | 509 | 24.4 | 114 | 330 | 34.5 | 240 | 392 | 61.2 | 601 | 3085 | 19.5 | 335 | 10.9 | 266 | 8.6 |
*All ovarian cases and those with ovarian cancer family history. Only cases with proven high grade were included where no further ovarian cancers were present in the family. +HGSOC, high-grade serous ovarian cancer; path avail, pathology available; TNT, triple-negative tumour.