Table 2.
Summary of tumor BRCA1/2 mutations and loss of heterozygosity (evaluable ITT population).
| Tumor BRCA1/2 mutations and LOH | Cohort 1 n (%) |
Cohort 2 n (%) |
Total N (%) |
|---|---|---|---|
| No. of evaluable patientsa | 32 | 28 | 60 |
| Only BRCA1 mutation(s)b | 18 (56.3) | 12 (42.9) | 30 (50.0) |
| Only BRCA2 mutation(s)c | 12 (37.5) | 16 (57.1) | 28 (46.7) |
| Both BRCA1 and BRCA2 mutation(s) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Neither BRCA1 nor BRCA2 mutation(s)d | 2 (6.3) | 0 (0.0) | 2 (3.3) |
| No. evaluable for BRCA zygositye | 23 | 24 | 47 |
| ≥1 BRCA1 or BRCA2 mutation with LOH | 21 (91.3) | 19 (79.2) | 40 (85.1) |
| ≥1 BRCA1 mutation with LOH | 12 (52.2) | 10 (41.7) | 22 (46.8) |
| ≥1 BRCA2 mutation with LOH | 9 (39.1) | 9 (37.5) | 18 (38.3) |
| No BRCA1 or BRCA2 mutations with LOH | 2 (8.7) | 5 (20.8) | 7 (14.9) |
Cohort 1 comprised patients with response to prior platinum and no progression within 8 weeks and Cohort 2 comprised patients who received ≥3 platinum-free cytotoxic regimens. Evaluable ITT population includes all the patients with tumor samples suitable for genomic evaluation and analyzed using FoundationOne® CDx assay. One patient exhibited no known/likely pathogenic BRCA mutation but did exhibit a pathogenic BRCA1 CNA per FoundationOne® CDx. However, based on further examination of primary tumor sequencing data by Foundation Medicine, this CNA was deemed to align with a germline BRCA1 del exons 13–15 mutation in the same patient, hence this subject was included in the BRCAmut tally for this table19.
BRCA1/2 breast cancer susceptibility gene 1 or 2, CNA copy number alteration, gBRCA1/2mut germline BRCA1/2 mutation, ITT intent-to-treat, LOH loss of heterozygosity, tBRCA1/2mut tumor BRCA1/2 mutation.
aThe percentages are calculated by using the number of evaluable patients in each cohort or the combined total number as the denominator.
bMedian (min, max) number of distinct BRCA1 mutations per patient in the only BRCA1 mutation category = 1(1,2).
cMedian (min, max) number of distinct BRCA2 mutations per patient in the only BRCA2 mutation category = 1(1,2).
dTwo patients without a tBRCA1/2mut had BRCA2 variants of unknown pathogenic significance distinct from their gBRCA2mut: First patient: gBRCA2mut = 9345 G > C (P3039P) with tBRCA2variant = 5070 A > C (K1690N); Second patient: gBRCA2mut = duplicate exons 15–18 with tBRCA2variant = 7052 C > T (A2351V).
eThe percentages are calculated by using the number of evaluable patients in each cohort as the denominator. LOH is predicted by somatic-germline-zygosity analysis (Foundation Medicine, Inc.). LOH can refer to either copy-neutral LOH status (i.e., homozygous, both alleles carry the same variant in the tumor) or to hemizygous status (i.e., loss of one allele in the tumor). There were no patients who exhibited mutations in both BRCA1 and BRCA2.