Table 3.
Cumulative Lifetime Risk of (in %) and 95% CI of Breast Cancer in BRCA1/2 Carriers by Age 70 Years by Method of Analysis
| Bias Correction Method* |
BRCA1 |
BRCA2 |
||||
|---|---|---|---|---|---|---|
| n/N | CLTR | 95% CI | n/N | CLTR | 95% CI | |
| Kaplan-Meier analysis | ||||||
| Including index patients | 161/395 | 66.4 | 58.7 to 74.0 | 101/232 | 72.9 | 63.2 to 81.8 |
| Including index patients and including proportion of untested FDRs | 212/590 | 54.5 | 49.0 to 60.3 | 139/332 | 63.6 | 56.2 to 70.9 |
| Including index patients and including all untested FDRs | 218/744 | 43.6 | 38.9 to 48.5 | 144/408 | 51.9 | 45.5 to 58.6 |
| Excluding index patients | 87/298 | 54.3 | 45.2 to 64.0 | 46/170 | 55.7 | 43.0 to 69.1 |
| Excluding index patients and including proportion of untested FDRs | 138/493 | 45.4 | 39.4 to 52.0 | 84/270 | 52.1 | 43.6 to 61.2 |
| Excluding index patients and including all untested FDRs | 144/647 | 34.9 | 31.1 to 40.2 | 89/346 | 40.5 | 33.7 to 48.1 |
| Kaplan-Meier incident cases analysis† | ||||||
| Excluding index patients | 23/167 | 83.4 | 62.5 to 96.2 | 10/114 | 86.0 | 56.9 to 99.0 |
| Excluding index patients and including proportion of untested FDRs | 25/232 | 75.6 | 56.3 to 90.9 | 10/139 | 77.6 | 51.5 to 95.5 |
| Excluding index patients and including all untested FDRs | 26/289 | 67.2 | 49.1 to 84.2 | 10/137 | 72.7 | 47.6 to 92.7 |
| Kaplan-Meier analysis with bootstrapping at family level | ||||||
| Including index patients and including proportion of untested FDRs | 208/495 | 72.8 | 65.4 to 80.2 | 139/332 | 80.4 | 71.6 to 89.3 |
| Excluding index patients and including proportion of untested FDRs | 136/403 | 66.0 | 57.5 to 74.4 | 84/270 | 70.5 | 54.3 to 86.6 |
| Frailty model analysis | ||||||
| Including index patients | 161/395 | 67.4 | 59.6 to 75.1 | 101/232 | 73.9 | 64.2 to 83.7 |
| Including index patients and including all untested FDRs | 218/744 | 44.7 | 39.4 to 49.9 | 144/408 | 53.3 | 46.5 to 60.2 |
| Excluding index patients | 87/298 | 54.4 | 45.0 to 63.8 | 46/170 | 56.2 | 41.7 to 70.7 |
| Excluding index patients and including all untested FDRs | 144/647 | 35.1 | 29.8 to 40.4 | 89/346 | 41.3 | 33.9 to 48.8 |
| Modified segregation analysis‡ | ||||||
| Joint likelihood conditioned on genotype of index carriers and all phenotypes | 156/1,060 | 36.6 | 18.8 to 50.4 | 96/604 | 42.4 | 14.9 to 61.0 |
| Joint likelihood conditioned on genotype of index patients and all phenotypes | 158/1,074 | 40.7 | 25.6 to 52.8 | 98/615 | 49.4 | 30.5 to 63.1 |
| Joint likelihood conditioned on genotype of index patients and phenotypes at time of index patients' DNA test | 158/1,074 | 57.1 | 43.7 to 67.3 | 98/615 | 53.2 | 34.8 to 66.4 |
| Retrospective likelihood conditioned only on all phenotypes | 230/1,171 | 52.8 | 43.2 to 60.8 | 151/677 | 67.4 | 55.8 to 75.9 |
Abbreviations: CLTR, cumulative lifetime risk; FDRs, first-degree relatives; n, total number of events (ie, female breast cancer); N, total number of women at risk in the analysis.
Right censoring at date of first event (which might be diagnosis of breast cancer, ovarian cancer, risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, or last contact or death).
Incident case analysis includes only years at risk and events after the date of the first positive DNA test in the family.
Modeling the probability of breast cancer conditioned on the genotype and phenotype of the index patients or index carriers, and/or the phenotype of relatives.