Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 DongAn Rd, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Ovarian Res. 2023 Mar 15;16(1):53. doi: 10.1186/s13048-023-01129-x.
Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population.
We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients.
The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03).
The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy.
同源重组缺陷（HRD）是卵巢癌患者接受 PARP 抑制剂治疗或乳腺癌患者接受一线铂类化疗的预测性生物标志物。然而，关于 HRD 作为生物标志物在卵巢癌患者中进行铂类治疗预测的研究有限，尤其是在中国人群中。
我们研究了 240 名中国高级别浆液性卵巢癌（HGSOC）患者中 HRD 状态与铂类化疗反应之间的关系。
铂类敏感患者的 HRD 评分高于铂类耐药患者，但无统计学意义（中位数：42.6 比 31.6，p=0.086）。HRD+BRCA 突变肿瘤和 HRD+BRCAwt 肿瘤的铂类敏感率较高（HRD+BRCA 突变：97%，p=0.004；HRD+BRCAwt：90%，p=0.04），而 HRD-BRCAwt 肿瘤的铂类敏感率为 74%。我们还发现，铂类敏感患者倾向于富集于 BRCA 突变或非 BRCA HRR 途径基因突变患者中（BRCA：93.6%比 75.4%，p<0.001；非 BRCA HRR：88.6%比 75.4%，p=0.062）。HRD 状态阳性患者的 PFS 明显长于 HRD 状态阴性患者（中位 PFS：30.5 个月比 16.8 个月，对数秩检验 p=0.001）。即使是 BRCAwt 患者，HRD 阳性也与 HRD 阴性组相比具有更好的 PFS（中位：27.5 个月比 16.8 个月，对数秩检验 p=0.010）。此外，我们发现 BRCA1 的 DNA 结合域（DBD）中存在致病性突变的患者与其他突变患者相比，FPS 有所提高。（p=0.03）。
HRD 状态可作为中国 HGSOC 患者接受一线铂类化疗的独立预后因素。
