Table 1.
Demographic and Disease Characteristics of the Patients at Baseline.*
| Characteristic | Olaparib (N = 921) | Placebo (N = 915) |
|---|---|---|
| Median age (interquartile range) — yr | 42 (36–49) | 43 (36–50) |
| Germline BRCA mutation — no. (%)† | ||
| BRCA1 | 657 (71.3) | 670 (73.2) |
| BRCA2 | 261 (28.3) | 239 (26.1) |
| BRCA1 and BRCA2 | 2 (0.2) | 5 (0.5) |
| Missing data | 1 (0.1) | 1 (0.1) |
| Previous adjuvant or neoadjuvant chemotherapy — no. (%) | ||
| Adjuvant | 461 (50.1) | 455 (49.7) |
| Neoadjuvant | 460 (49.9) | 460 (50.3) |
| Regimen with both anthracycline and taxane | 871 (94.6) | 849 (92.8) |
| Anthracycline regimen, without taxane | 7 (0.8) | 13 (1.4) |
| Taxane regimen, without anthracycline | 43 (4.7) | 52 (5.7) |
| Regimen not reported | 0 | 1 (0.1) |
| <6 Cycles of neoadjuvant or adjuvant chemotherapy | 7 (0.8) | 15 (1.6) |
| Platinum-based neoadjuvant or adjuvant therapy | ||
| No | 674 (73.2) | 676 (73.9) |
| Yes | 247 (26.8) | 239 (26.1) |
| Concurrent hormone therapy (hormone-receptor–positive patients only) — no./total no. (%) | 146/168 (86.9) | 142/157 (90.4) |
| Hormone-receptor status — no. (%)‡ | ||
| Hormone-receptor positive and HER2 negative§ | 168 (18.2) | 157 (17.2) |
| Triple-negative breast cancer¶ | 751 (81.5) | 758 (82.8) |
| Menopausal status (women only) — no./total no. (%) | ||
| Premenopausal | 572/919 (62.2) | 553/911 (60.7) |
| Postmenopausal | 347/919 (37.8) | 358/911 (39.3) |
| Surgery for primary breast cancer — no. (%) | ||
| yMastectomy | 698 (75.8) | 673 (73.6) |
| Conservative surgery only | 223 (24.2) | 240 (26.2) |
| Missing data | 0 | 2 (0.2) |
Further information on baseline characteristics is provided in Table S6 in the Supplementary Appendix. Percentages may not total 100 because of rounding. HER2 denotes human epidermal growth factor receptor 2.
For a detailed description of local and central Myriad BRCA testing in patients enrolled in the trial, see Figure S2. Variant interpretation by Myriad Genetics (BRCAnalysis) (1564 patients) and BGI Genomics (247 patients) was performed with the use of multiple established databases (e.g., ClinVar, ClinGen, and ENIGMA) and published and internal functional and clinical data, compliant with American College of Medical Genetics published guidelines. The 24 pathogenic or likely pathogenic variants from local laboratories without central Myriad confirmation were confirmed by the OlympiA genetics advisory committee with the use of published databases as above. Discordant data are referred to Figure S2, and numbers are shown in Table S3. Table S2B lists pathogenic or likely pathogenic (deleterious or suspected deleterious) BRCA1 and BRCA2 variants that occurred in more than 1 patient.
Hormone-receptor status was defined by local test results.
The original protocol that was activated in 2014 was developed for HER2-negative patients but included only patients with triple-negative breast cancer after regulatory review. When the safety rationale with respect to recurrence risk relative to combination therapy with olaparib and endocrine therapy was accepted by regulators, the protocol was amended in 2015 to include patients with high-risk hormone-receptor–positive disease and to increase the sample size to the current number of 1800 patients (see the protocol). The first patient with hormone-receptor–positive disease was enrolled in December 2015.
Triple-negative breast cancer was defined in the eligibility criteria as estrogen-receptor negative and progesterone-receptor negative, as indicated by immunohistochemical (IHC) nuclear staining of less than 1%, and HER2 negative (not eligible for anti-HER2 therapy), as indicated by one of the following: an IHC score of 0 or 1+; an IHC score of 2+ and HER2-nonamplified disease on in situ hybridization (ISH) with a ratio of less than 2.0 and, if reported, an average HER2 copy number of fewer than 4 signals per cell; or HER2-nonamplified disease on ISH with a ratio less of than 2.0 and, if reported, an average HER2 copy number of fewer than 4 signals per cell (without IHC). Two patients (both in the olaparib group) were excluded from the summary of the subgroup with triple-negative breast cancer because they did not have confirmed HER2-negative status.