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Objective: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group., Methods: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed)., Results: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36)., Conclusions: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications., Competing Interests: Declaration of competing interest The following authors have no disclosures relating to this manuscript: Omali Pitiyarachchi, Laura Holman, Paul DiSilvestro, Mark Morgan, William Tew, Christine Lee, Meredith Newton, Babak Edraki, Thomas Reid and Jay Carlson. Peter J. Ansell and Minh H Dinh are AbbVie employees receiving stock or stock options. Robert L. Coleman: has received grants or contracts from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech, Karyopharm; consulting fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Karyopharm, Roche/Genentech, Novocure, Merck, Abbvie, Novocure; royalties or licenses with Up-To-Date; payment or honoraria for speakers bureaus from AstraZeneca, Clovis, Roche/Genentech, Merck; participation in data safety monitoring or advisory boards from NRG Oncology, Elsai/BMS; leadership or fiduciary role in Onxeo/Valerio, Vaniam Group, GOG Foundation, International Gynecologic Cancer Society, OCNA, Ovarcome. Charles A. Leath III: Grant to institution provided by National Institutes of Health (NCI UG1 CA233330). Theresa Werner has received consulting fees from Mersana; and research funding to the institution - AbbVie, Acrivon, Astra Zeneca, BluePrint, Clovis Oncology, Genmab, GSK-Tesaro, Mersana, Repare Therapeutics, Roche-Genentech. Mary Cunningham: funds to institution provided by Abbvie, AstraZeneca, Clovis Oncology, Tesaro, Vascular Biogenics; and spouse is a stockholder of Intuitive Surgical. Peter Lim: has received payment or honoraria for Speakers Bureau from Astra Zeneca and Merck and is on Advisory Boards for Astra Zeneca, Clovis, Mersana, OncoC4, Immunogen. Joyce Barlin: has received payment/honoraria for Speakers Bureaus from Astra Zeneca and Merck and is on Advisory Boards for Astra Zeneca, Clovis, Mersana, OncoC4, Immunogen. Nicola M. Spirtos: has received institutional grants from NRG and the GOG Foundation. Krishnansu S. Tewari: reports grants to institution (UC Irvine) provided by AbbVie; consulting fees from Merck, Astra Zeneca, Eisai, Seagen, GSK; and payment/honoraria for Speakers Bureaus from Merck, Astra Zeneca, Eisai, Seagen, GSK. Mitchell Edelson: has received funding to attend meetings from Intuitive Surgical; received stock options from Merck when employed. Spouse was a salaried employee at Merck until 8/2022 and spouse is a salaried employee at Pfizer since 3/2023. Michael Friedlander: has received consulting fees from Astra Zeneca, Novartis and GSK; has consulted without payment for Incyclix; has received payment or honoraria for Speakers Bureaus from Astra Zeneca, GSK and MSD; has participated on Data Safety Monitoring or Advisory Boards for AGITG IDSMB and ENDO-3; received institutional support in the form of research grants from Astra Zeneca, Beigene and Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients., Methods: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC., Results: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (<70 years), 7% (n = 62) BRCA1/2 and 2% (n = 19) other HR-related genes (p = 0.36). The overall frequency of somatic BRCA1/2 PVs was similar in INOVATe (n = 25; 7.7%) and somatic-only BRCA2 PVs were again found in older patients compared with BRCA1 (median age: at testing, 70 vs 63 years; at diagnosis, 68 vs 60 years)., Conclusions: The overall frequency of somatic-only PVs in HR-related genes was similar in older and younger patients with HGSC, highlighting the importance of somatic testing irrespective of age. Limiting somatic testing by age may exclude patients who could benefit from maintenance poly(ADP-ribose) polymerase (PARP) inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ADeF has received grant funding from AstraZeneca for unrelated work. All other authors reported no conflicts of interest related to this work., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Patients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS., Methods: Data from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS., Results: Of 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23-28%) and LTDFS ≥10 years was 18% (95% CI, 16-20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis., Conclusions: Approximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes., Competing Interests: Declaration of Competing Interest MF reports honoraria from Astra Zeneca;GSK;Novartis;MSD;Takeda;Lilly;Eisei for advisory boards/consulting.Speaker fees from Astra Zeneca;GSK and MSD. Institutional research funding from Astra Zeneca;Novartis and Beigene. Travel expenses for Astra Zeneca. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cancer patients treated with neurotoxic chemotherapy are at risk of developing neurological symptoms that can impact functional capacity and quality of life. However, there are no standardised pathways to assess and manage chemotherapy-induced peripheral neurotoxicity (CIPN). This study aimed to determine consensus on statements regarding a CIPN assessment and management clinical pathway., Methods: A CIPN clinical pathway (CIPN-path) was developed and reviewed by an expert multi-disciplinary panel and consumers. Agreement with 18 statements regarding four content themes (pretreatment review, screening and assessment, management and referral, and CIPN-path feasibility) were assessed by 70 Australian respondents (68 health professionals, 2 consumers), using a 2-stage Delphi survey process to reach consensus. Respondents rated statements using a 5-point Likert scale to determine the level of agreement, with consensus defined as ≥ 80% of respondents agreeing with each statement., Results: The consensus was reached for 14 of 18 items after stage 1 and all items after stage 2. Feedback was obtained for all items to refine the CIPN-path. There was an agreement on important characteristics of the CIPN-path, including pretreatment screening, regular patient-reported assessment, and a stepped-care approach to investigating and managing symptom burden. There was a lack of agreement on who should oversee CIPN assessment, which may differ according to the structure and resources of each site., Conclusions: There was an overall agreement concerning the CIPN-path to assess and manage CIPN, which may be adapted accordingly to the resources of each clinic. The CIPN-path may assist teams across different health services in identifying CIPN symptoms, aiding decision-making, and reducing morbidity from CIPN., (© 2022. The Author(s).)

After a diagnosis of breast cancer women with increased genetic risk often have a risk reducing contralateral mastectomy, and may opt for a nipple or skin sparing mastectomy with immediate reconstruction. A variable amount of residual breast tissue remains which may substantially increase in volume during pregnancy. Whether this increases later risk of breast cancer is unknown. We describe the clinical details of 3 patients with a history of unilateral breast cancer, including 2 with a BRCA mutation, who developed hyperplasia of residual breast tissue in the 3rd trimester of a later pregnancy. They all had a delayed contralateral risk reducing skin sparing mastectomy and immediate reconstruction. Pregnancy occurred some years later. We summarise their management, review the literature and raise questions for discussion. All developed prominent hyperplasia of breast tissue in the 3rd trimester that was clinically obvious asymmetrical breast swelling in the reconstructed contralateral breast. MRI demonstrated substantial breast tissue. The risk of breast cancer, particularly in those at high genetic risk developing in the residual breast tissue is unknown but in view of the volume, breast tissue was excised postpartum. This phenomenon of pregnancy induced hyperplasia of breast tissue after risk reducing mastectomy is not well described .There is residual breast tissue following a risk reducing subcutaneous mastectomy. The risk factors include age and skin flap thickness. MRI can demonstrate the residual breast tissue. Pregnancy induced hyperplasia of residual breast tissue may occur after risk reducing mastectomy with a hypothetical increased risk of subsequent breast cancer., (Copyright © 2021. Published by Elsevier Ltd.)