HRD

In the final PRIMA PRO analysis, results confirmed that niraparib first-line maintenance did not negatively affect HRQOL versus placebo. Disease progression caused sustained HRQOL deterioration across arms, emphasizing the clinical importance of extending progression-free survival to preserve patient HRQOL.

This case expands the morphologic spectrum of Stensen's duct carcinoma, underscores the challenges in clinical, radiologic, and pathologic interpretation of masses at this site, and suggests a potential association between homologous recombination deficiency and this translocation-associated malignancy.

P1, N=19, Not yet recruiting, Shanghai Gynecologic Oncology Group

HRD represents a reliable independent prognostic biomarker in HR+/HER2- breast cancer in this cohort, with an inverse association with TILs suggesting immune evasion. Its potential impact on prognosis and treatment requires further validation in prospective clinical trials.

These data demonstrate that targeting HRD yields promising outcomes in stage III, HER2-negative, HRD breast cancer and that intensified chemotherapy with autologous stem cell rescue does not provide any advantage over state-of-the-art chemotherapy plus olaparib.

After cytoreductive surgery, she received postoperative HIPEC followed by adjuvant chemotherapy nab-paclitaxel and carboplatin, then sequential maintenance therapy with bevacizumab followed by olaparib based on homologous recombination deficiency (HRD) positivity. The patient remained progression-free with good performance status at 24 months of follow-up. This hypothesis-generating case suggests that for selected patients with OCS, a multimodal approach incorporating aggressive cytoreductive surgery, postoperative HIPEC, and HRD-guided sequential maintenance therapy may warrant further investigation.

GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation.

The apparent BRCT enrichment observed in earlier unfiltered analyses appears to be driven by VUSs rather than pathogenic variants, highlighting the methodological necessity of pathogenicity filtering for clinically actionable inference. These findings provide cohort-scale supportive evidence for emerging clinical guidelines that recommend broader BRCA1/2 testing across breast cancer subtypes.

In the BRCA+ high-risk population, olaparib monotherapy (median PFS 41.2 months) and olaparib plus bevacizumab (median PFS 42.5 months) demonstrated the greatest PFS benefit, marginally outperforming niraparib (median PFS 31.2 months). RMST analysis also indicated an advantage of 8.5 months for the combination, though this did not reach statistical significance. PARPi treatment benefit in ovarian cancer is meaningfully influenced by genetic profile and relapse risk, supporting biomarker-driven treatment selection in clinical practice.

The locally semi-automated HRD workflow demonstrated high analytical concordance with established commercial assays in evaluable cases. Operational advantages related to workflow flexibility and local reanalysis support its potential implementation in routine molecular diagnostics.

Collectively, our findings underscore the necessity for rigorous optimization of data processing workflows and threshold definitions to ensure consistency, comparability, and reproducibility across HRD classification platforms.

The phase III KEYNOTE-B96 trial in platinum-resistant disease demonstrated a progression-free survival benefit in the intention-to-treat population and an overall survival benefit in tumors with programmed death ligand 1 (PD-L1) combined positive score ≥1 when pembrolizumab was paired with weekly paclitaxel with or without bevacizumab, underscoring the value of an immunomodulatory chemotherapy backbone in earlier lines. We explain why single-analyte biomarkers-PD-L1, tumor mutational burden, homologous recombination deficiency/BRCA1/2-have not reliably enriched benefit and outline a multidimensional approach integrating genomic scars (e.g., mutational signature 3), immune functional state (Immunoscore, CD8⁺ tumor-infiltrating lymphocyte density and CD8⁺: regulatory T-cell ratio), and spatial architecture (inflamed, excluded, desert phenotypes). This framework aims to move beyond the all-comer era toward context-informed precision immunotherapy in ovarian cancer.