Background: HRD is a key biomarker in ovarian cancer, predicting response to PARP inhibitors. However, it remains unclear whether HRD-positive patients differ from HRD-negative patients in terms of clinical characteristics in PARP inhibitor-naïve populations. This study aims to evaluate platinum-sensitive PARP-inhibitor naïve ovarian cancer patients’ clinical characteristics and survival outcomes based on HRD status. Secondly, to investigate whether platinum-resistant patients with homologous recombination repair (HRR) gene mutations are HRD-positive. Methods: Two distinct HRD algorithms—an in-house genomic instability score (GIS) and the normalized large-scale state transitions score (nLST)—were used to stratify patients as HRD-positive or HRD-negative. Clinical data and survival in PARP inhibitor-naïve, platinum-sensitive HGSC patients were analyzed. Results: A total of 71 platinum-sensitive PARP-inhibitor naïve patients were analyzed. By in-house GIS, 37 patients (52%) were classified as HRD-positive and 34 (48%) as HRD-negative. Using nLST, 43 (61%) were HRD-positive and 28 (39%) were HRD-negative. Our analysis revealed no significant differences in clinical parameters or survival between HRD-positive and HRD-negative platinum-sensitive patients. The only observed difference was that somaticBRCA1/2-mutated patients were younger. In the subgroup of six platinum-resistant patients harboring HRR gene mutations, four patients (67%) were classified as HRD positive. Conclusions: Our findings suggest that HRD status does not significantly influence clinical characteristics or survival outcomes in platinum-sensitive, PARP inhibitor-naïve HGSC patients. As some platinum-resistant patients with HRR gene mutations were HRD positive; this subgroup may benefit from further investigation into the potential effect of PARP inhibitors.
背景：同源重组缺陷（HRD）是卵巢癌的关键生物标志物，可预测对PARP抑制剂的治疗反应。然而，在未接受过PARP抑制剂治疗的人群中，HRD阳性患者与HRD阴性患者在临床特征上是否存在差异尚不明确。本研究旨在基于HRD状态，评估未使用过PARP抑制剂、对铂类敏感的卵巢癌患者的临床特征及生存结局；其次，探讨携带同源重组修复（HRR）基因突变的铂类耐药患者是否为HRD阳性。方法：采用两种不同的HRD算法——内部基因组不稳定性评分（GIS）和标准化大规模状态转换评分（nLST），将患者分为HRD阳性或HRD阴性。对未使用过PARP抑制剂、对铂类敏感的高级别浆液性癌（HGSC）患者的临床数据及生存情况进行分析。结果：共纳入71例对铂类敏感、未使用过PARP抑制剂的患者进行分析。根据内部GIS算法，37例患者（52%）被归类为HRD阳性，34例（48%）为HRD阴性；使用nLST算法时，43例（61%）为HRD阳性，28例（39%）为HRD阴性。分析显示，在对铂类敏感的患者中，HRD阳性与HRD阴性患者在临床参数或生存方面均无显著差异。唯一观察到的差异是体细胞BRCA1/2突变患者更为年轻。在6例携带HRR基因突变的铂类耐药患者亚组中，4例患者（67%）被归类为HRD阳性。结论：我们的研究结果表明，HRD状态对铂类敏感、未使用过PARP抑制剂的HGSC患者的临床特征或生存结局无显著影响。由于部分携带HRR基因突变的铂类耐药患者为HRD阳性，该亚组患者可能受益于进一步研究PARP抑制剂的潜在疗效。
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