Table A2.
Estimated Cumulative Lifetime Risks and Relative Bias by Age 70 Years for 50 Simulated Datasets
| Bias Correction Method* |
BRCA1 Carriers |
BRCA2 Carriers |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| CLTR |
Relative Bias (%) |
CLTR |
Relative Bias (%) |
|||||||
| Mean | SD of Means | Mean SD | Mean | SD | Mean | SD of Means | Mean SD | Mean | SD | |
| Reference estimate population | 48.1 | 1.8 | 1.6 | −15.6 | 2.1 | 54.4 | 2.9 | 3.6 | −18.2 | 4.0 |
| Reference estimate clinic | 57.0 | 2.3 | 2.9 | 0 | 0 | 66.6 | 3.9 | 7.6 | 0 | 0 |
| Kaplan-Meier analysis | ||||||||||
| Including index patients | 61.5 | 2.4 | 3.7 | 7.9 | 1.9 | 71.0 | 3.8 | 9.8 | 6.6 | 3.4 |
| Including index patients and including proportion of untested FDRs | 58.1 | 2.3 | 3.0 | 2.0 | 2.1 | 67.2 | 4.1 | 8.0 | 0.9 | 3.6 |
| Including index patients and including all untested FDRs | 49.5 | 2.0 | 1.8 | −13.1 | 1.8 | 58.6 | 3.4 | 4.7 | −11.9 | 3.5 |
| Excluding index patients | 46.0 | 3.8 | 3.2 | −19.4 | 4.6 | 55.4 | 6.7 | 9.7 | −17.0 | 8.5 |
| Excluding index patients and including proportion of untested FDRs | 44.2 | 3.5 | 2.5 | −22.4 | 4.5 | 51.2 | 7.3 | 6.9 | −23.2 | 9.5 |
| Excluding index patients and including all untested FDRs | 35.4 | 2.6 | 1.2 | −38.0 | 3.2 | 42.9 | 4.7 | 3.4 | −35.6 | 6.2 |
| Kaplan-Meier incident case analysis† | ||||||||||
| Excluding index patients | 51.9 | 4.5 | 4.7 | −9.0 | 6.5 | 57.9 | 8.3 | 12 | −13.2 | 11.1 |
| Excluding index patients and including proportion of untested FDRs | 51.4 | 4.2 | 4.3 | −9.9 | 6.1 | 55.9 | 7.5 | 10.4 | −16.1 | 10.2 |
| Excluding index patients and including all untested FDRs | 46.7 | 3.9 | 2.9 | −18.2 | 5.7 | 53.1 | 5.4 | 7.4 | −20.3 | 7.0 |
| Kaplan-Meier analysis with bootstrapping at family-level | ||||||||||
| Including index patients and including proportion of untested FDRs | 66.0 | 2.7 | 2.4 | 15.8 | 2.2 | 74.1 | 4.0 | 3.8 | 11.2 | 3.6 |
| Excluding index patients and including proportion of untested FDRs | 57.0 | 4.4 | 3.9 | 0.0 | 5.7 | 65.4 | 6.1 | 6.6 | −1.8 | 8.7 |
| Frailty model analysis | ||||||||||
| Including index patients | 61.5 | 2.2 | 2.2 | 7.9 | 2 | 70.6 | 3.9 | 3.8 | 6.0 | 3.4 |
| Including index patients and including all untested FDRs | 50.0 | 1.8 | 1.8 | −12.3 | 1.9 | 58.6 | 3.5 | 3.2 | −12.0 | 3.6 |
| Excluding index patients | 46.1 | 4 | 3.6 | −19.3 | 5.3 | 55.5 | 6.8 | 7.4 | −16.7 | 8.9 |
| Excluding index patients and including all untested FDRs | 36.5 | 2.5 | 2.3 | −36.0 | 3.1 | 43.8 | 4.9 | 4.6 | −34.3 | 6.3 |
| Modified segregation analysis‡ | ||||||||||
| Joint likelihood conditioned on genotype of index carriers and all phenotypes | 43.3 | 4.7 | 7.7 | −23.9 | 8.5 | 52.4 | 10.9 | 14.2 | −21.1 | 17.0 |
| Joint likelihood conditioned on genotype of index patients and all phenotypes | 43.3 | 4.7 | 7.7 | −23.9 | 8.5 | 52.4 | 10.9 | 14.2 | −21.2 | 16.9 |
| Joint likelihood conditioned on genotype of index patients and phenotypes at time of index patients' DNA test | 51.5 | 3.5 | 3.7 | −9.7 | 5.1 | 59.0 | 5.7 | 7.2 | −11.5 | 6.8 |
| Retrospective likelihood conditioned only on all phenotypes | 58.5 | 2.3 | 3.4 | 2.7 | 2.2 | 68.3 | 4.1 | 4.3 | 2.5 | 3.4 |
Abbreviations: CLTR, cumulative lifetime risk; FDRs, first-degree relatives; NA, not applicable.
*
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.