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• W4362541842 abstract "<div>Abstract<p>The current study evaluated three biomarkers [homologous recombination deficiency (HRD), tumor BRCA1/2 (tBRCA) mutations, and CCNE1 copy-number variation (CNV)] in ovarian tumors from patients enrolled on the SCOTROC4 clinical trial for associations with outcome following carboplatin monotherapy. Ovarian tumors (<i>n</i> = 250), with high-grade serous (HGSOC) subgroup analysis (<i>n</i> = 179) were classified as HRD positive (HRD score ≥42 or tBRCA mutation) and as CCNE1 amplification positive (CCNE1 CNV score >2.4). Seventy-four (30%) tumors were HRD positive, including 34 (14%) with tBRCA mutations. Forty-seven (19%) were CCNE1 amplification positive, all of which were tBRCA wild-type. HRD and tBRCA, but not CCNE1 amplification, were significantly associated with CA125 complete response in the entire cohort (HRD, <i>P</i> = 0.00015; tBRCA <i>P</i> = 0.0096), and the HGSOC subgroup (HRD, <i>P</i> = 0.0016; tBRCA <i>P</i> = 0.032). HRD and lack of CCNE1 amplification were associated with improved progression-free survival (PFS) and overall survival (OS) in the full cohort and HGSOC subgroup (HRD, <i>P</i> = 0.00021; CCNE1 status <i>P</i> = 0.038). HRD remained significant for OS and PFS after adjusting for clinical factors, while CCNE1 status only remained significant for PFS. Patients with HRD-positive tumors had greater PFS and OS benefit from platinum dose intensification than HRD-negative tumors (<i>P</i> = 0.049 and <i>P</i> = 0.035, respectively). An alternative exploratory HRD score threshold (≥33 or tBRCA mutation) was also significantly associated with both PFS and OS in the HGSOC subset.</p><p><b>Implications:</b> HRD, tumor BRCA1/2 mutations, and absence of CCNE1 amplification are associated with improved survival of ovarian cancer patients treated with platinum monotherapy and HRD-positive patients may benefit from platinum dose intensification. <i>Mol Cancer Res; 16(7); 1103–11. ©2018 AACR</i>.</p></div>" @default.
• W4362541842 created "2023-04-06" @default.
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• W4362541842 date "2023-04-03" @default.
• W4362541842 modified "2023-10-16" @default.
• W4362541842 title "Data from Biomarker Assessment of HR Deficiency, Tumor <i>BRCA1/2</i> Mutations, and <i>CCNE1</i> Copy Number in Ovarian Cancer: Associations with Clinical Outcome Following Platinum Monotherapy" @default.
• W4362541842 doi "https://doi.org/10.1158/1541-7786.c.6541371" @default.
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