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Background <p>Germline <i>BRCA</i> (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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月27日

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  • Kosuke Yoshida,
  • Hajime Araki,
  • Yurika Yamada,
  • Yoshiki Masahashi,
  • Emiri Miyamoto,
  • Komei Katayama,
  • Mei Kubokawa,
  • Kazumasa Mogi,
  • Masato Yoshihara,
  • Yukari Nagao,
  • Satoshi Tamauchi,
  • Akira Yokoi,
  • Nobuhisa Yoshikawa,
  • Kaoru Niimi,
  • Hiroaki Kajiyama

摘要

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.