Association of germline BRCA and homologous recombination deficiency with hematologic toxicity during platinum-taxane chemotherapy in ovarian cancer.

BACKGROUND

Germline BRCA (gBRCA) mutations and homologous recombination deficiency (HRD) are critical factors affecting treatment response; however, their association with hematologic toxicity remains controversial. This study assessed the interplay between these molecular features and hematologic adverse events during platinum-taxane chemotherapy.

METHODS

We retrospectively reviewed 62 patients with stage III-IV ovarian cancer between 2022 and 2024. After excluding 8 patients, 54 patients were stratified according to gBRCA and HRD status, and hematologic adverse events were evaluated for up to six treatment cycles. Moreover, meta-analysis was performed to integrate previously published data.

RESULTS

First, after excluding patients with uncertain gBRCA status, eight gBRCA mutation carriers were compared with 33 confirmed non-carriers. gBRCA mutation carriers tended to exhibit lower neutrophil counts during treatment; however, no statistically significant differences in hematologic toxicities were observed across treatment cycles. In the pooled meta-analysis, gBRCA mutation carriers demonstrated significantly increased odds of neutropenia (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.16-2.44) and G-CSF use (OR 3.09, 95% CI 1.19-8.03), whereas no significant associations were observed for anemia, thrombocytopenia, dose delay, or dose reduction. Second, 23 HRD-positive patients and 15 HRD-negative patients were analyzed. HRD-positive patients did not demonstrate increased hematologic toxicity compared with HRD-negative patients. Although baseline hemoglobin levels were lower in HRD-positive patients, these differences preceded chemotherapy initiation.

CONCLUSION

This study provides real-world evidence of a modestly increased risk of neutropenia and G-CSF use in gBRCA carriers during platinum-taxane chemotherapy; however, these differences did not appear to compromise treatment delivery.