Gynecologic oncology最新文献

{"title":"Update on contemporary treatment for newly diagnosed stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC).","authors":"David M Gershenson, Kimberly Burns, Charlotte Sun","doi":"10.1016/j.ygyno.2025.09.011","DOIUrl":"https://doi.org/10.1016/j.ygyno.2025.09.011","url":null,"abstract":"","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"85-86"},"PeriodicalIF":4.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in pre-fellowship research productivity among matched gynecologic oncology fellows.","authors":"Monica J Janke, Annie Minns, Michaela M Pesce, Hannah D McLaughlin, Shitanshu Uppal, Jean H Siedel, Christopher X Hong","doi":"10.1016/j.ygyno.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.ygyno.2025.09.013","url":null,"abstract":"<p><strong>Objective: </strong>Research productivity is a key metric for evaluating gynecologic oncology fellowship candidates, but competitive benchmarks are unclear. We aimed to assess the pre-fellowship publication output of successfully matched gynecologic oncology fellows and trends over time.</p><p><strong>Methods: </strong>A cross-sectional study was conducted of trainees entering gynecologic oncology fellowship from 2018 to 2023. Trainee data were collected using online sources and communication with programs. PubMed was used to identify trainee publications, with publication year recorded relative to fellowship matriculation. Trends and differences in publication counts by matriculation year were assessed using Kruskal-Wallis and Cochran-Armitage tests. Multivariable Poisson regression assessed factors associated with total publications.</p><p><strong>Results: </strong>We identified 455 trainees. By the year of fellowship matriculation, 400 (87.9 %) trainees had at least one publication and 307 (67.5 %) had at least one first-author publication. The median number of total publications was 3 (IQR 1-6) and first-author publications was 1 (IQR 0-2). In assessing trends over time, median total publications increased from 2 (IQR 1-4) in 2018 to 4 (IQR 2-7) in 2023 (p < 0.01). Higher publication counts were associated with holding an additional advanced degree (incidence rate ratio [IRR] 1.44, 95 % CI 1.28-1.61) and training at university-based (IRR 2.43, 95 % CI 1.53-4.18) or community-based university affiliated residencies (IRR 2.31, 95 % CI 1.43-3.99) compared to community-based programs.</p><p><strong>Conclusions: </strong>Most trainees entering gynecologic oncology have published research prior to fellowship, with median publications increasing significantly over time. These findings suggest a growing competitiveness in the field and offer useful benchmarks for fellowship applicants and programs.</p>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"87-92"},"PeriodicalIF":4.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine leiomyosarcoma progression: A study of serial recurrences.","authors":"Tiffany Y Sia, David N Brown, Kathryn Miller, Christina Curtin, Pier Selenica, Arnaud Da Cruz Paula, Sara Moufarrij, Nadeem R Abu-Rustum, Mario M Leitao, Sarah Chiang, Britta Weigelt, Martee L Hensley","doi":"10.1016/j.ygyno.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.ygyno.2025.09.007","url":null,"abstract":"<p><strong>Background: </strong>Uterine leiomyosarcomas (uLMS) have high recurrence rates and are frequently characterized by genetic alterations affecting TP53 and RB1. We sought to compare the molecular profiles of primary uLMS and matched serial recurrences to assess tumor evolution.</p><p><strong>Methods: </strong>Patients diagnosed with uLMS between 1/1/2000-11/31/2020 who had primary tumor, ≥2 serial recurrences, and normal tissue available were identified. Samples were microdissected to enhance tumor purity and subjected to tumor-normal targeted DNA next-generation sequencing (NGS).</p><p><strong>Results: </strong>NGS was performed on 42 tumor samples from 10 patients. The median age at diagnosis was 54 years (range 30-69). The median number of recurrences was 3 (range 2-7). At least one homozygous deletion affecting RB1 (50 %), PTEN (30 %), TP53 (30 %), and/or BRCA2 (20 %), as well as clonal mutations affecting TP53 (30 %) and ATRX (10 %), were early events and present across subsequent samples of a given patient. In addition, non-pathogenic missense mutations were frequently shared across samples from a given case. In general, no additional cancer gene mutations were acquired during progression, including ESR1 hotspot mutations. Chromosomal instability was found to be significantly higher, albeit marginally so, in the recurrences compared to the patient-matched primary tumors (median fraction of genome altered 31 % v 29 %, p = 0.043).</p><p><strong>Conclusion: </strong>Primary uLMS and subsequent recurrences display genomic intra-individual concordance, with sustained driver cancer gene alterations over time. Chromosomal instability was higher in recurrent tumors.</p>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"77-84"},"PeriodicalIF":4.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silva pattern-guided proteomics reveals coordinated tumor-stroma remodeling in cervical adenocarcinoma","authors":"Sara M. Drayer ,&nbsp;Jonathan D. Ogata ,&nbsp;Sean Cronin ,&nbsp;Jordyn Tumas ,&nbsp;Saeid Movahedi-Lankarani ,&nbsp;Tamara Abulez ,&nbsp;Kelly A. Conrads ,&nbsp;Brian L. Hood ,&nbsp;Kathleen M. Darcy ,&nbsp;Christopher M. Tarney ,&nbsp;Kristen P. Bunch ,&nbsp;G. Larry Maxwell ,&nbsp;Thomas P. Conrads ,&nbsp;Nicholas W. Bateman ,&nbsp;Neil T. Phippen","doi":"10.1016/j.ygyno.2025.09.002","DOIUrl":"10.1016/j.ygyno.2025.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>Characterize proteome alterations within the tumor microenvironment of endocervical adenocarcinoma (ECA) stratified by Silva patterns.</div></div><div><h3>Methods</h3><div>Pathology review assigned 32 ECA as Silva A (n10), Silva B (n11) and Silva C (n11) tumors. Tumors underwent laser-microdissection enrichment of tumor and adjacent stromal cells followed by multiplexed, quantitative proteomic analyses. Comparative analyses were performed using hierarchical clustering and differential statistics with LIMMA and included prediction of pathway alterations and prioritization of proteins mapping as putative drug targets.</div></div><div><h3>Results</h3><div>Quantitative proteomic analyses identified 7300 proteins across all microcompartment samples. Unsupervised analyses showed stark differences between tumor and stroma populations and distinguished Silva C stroma from Silva patterns A/B. Tumors partitioned into clusters enriched for mitochondrial metabolism, immune signaling, or extracellular-matrix pathways; stroma formed complementary clusters characterized by matrix remodeling, immunity, or cell-cycle programs. Compared to patterns A and B, Silva C tumor and stroma cells exhibited large numbers of protein alterations and included candidates shared between tumor–stroma subpopulations (CPA3, NNMT), highlighting microenvironment reciprocity. Strong tumor-stroma correlations (Spearman ρ &gt; 0.83) underscored coordinated remodeling, and stromal protein alterations enriched in Silva C cases, suggested pronounced immune activation in these tumors. Candidate drug targets altered between Silva A and C tumors included PDGFRB, CDK4, EGFR, MAP2K1/2, and CEACAM5.</div></div><div><h3>Conclusions</h3><div>Silva C ECA exhibits a distinctive immune- and matrix-centric tumor–stroma axis based on proteome alterations observed. Tumor microenvironment-resolved proteomics identified Silva pattern-specific biomarkers and therapeutic vulnerabilities that warrant functional and clinical validation.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 66-76"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neoadjuvant chemotherapy in advanced-stage clear cell ovarian cancer: A GCIG multi-institutional retrospective cohort study","authors":"Sahana Somasegar ,&nbsp;Jiaqi Zhang ,&nbsp;Christina Fotopoulou ,&nbsp;Diletta Fumagalli ,&nbsp;Jalid Sehouli ,&nbsp;Charlie Gourley ,&nbsp;Michael Churchman ,&nbsp;Elena Ioana Braicu ,&nbsp;Amer Karam","doi":"10.1016/j.ygyno.2025.09.009","DOIUrl":"10.1016/j.ygyno.2025.09.009","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the impact of neoadjuvant chemotherapy (NACT) versus primary cytoreductive surgery (PCS) on surgical outcomes and survival in in patients with advanced clear cell ovarian cancer (OCCC).</div></div><div><h3>Methods</h3><div>We conducted a multi-institutional retrospective cohort study of 133 patients with FIGO stage IIIB–IVB OCCC treated between 2010 and 2024 at four tertiary cancer centers. Patients received either NACT followed by interval debulking surgery (<em>n</em> = 21) or PCS followed by adjuvant chemotherapy (<em>n</em> = 112). Statistical analyses included Wilcoxon rank-sum, Chi-square/Fisher's exact test, Kaplan–Meier estimates, and log-rank test.</div></div><div><h3>Results</h3><div>Baseline characteristics were similar, although NACT patients had worse ECOG performance status (<em>p</em> = 0.019). Complete resection (RD0) was achieved in 48 % of NACT patients and 67 % of PCS patients (<em>p</em> = 0.21). Median PFS was 11.0 months with NACT and 12.4 months with PCS (<em>p</em> = 0.55); median OS was 23.0 and 27.4 months, respectively (<em>p</em> = 0.15). Cytoreduction to RD ≤10 mm was associated with improved OS compared with RD &gt;10 mm (27.4 vs 10.0 months, <em>p</em> = 0.037), but not with improved PFS. Patients with RD0 had numerically longer OS and PFS compared to those with RD &gt; 0, though not statistically significant.</div></div><div><h3>Conclusion</h3><div>In this multi-institutional cohort, advanced OCCC was associated with poor survival regardless of treatment approach. NACT did not significantly improve resectability or survival compared with PCS. However, maximal surgical effort and achieving RD ≤10 mm or RD0 were associated with better outcomes, underscoring the prognostic importance of cytoreduction and the urgent need for histology-specific trials.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 59-65"},"PeriodicalIF":4.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIB3 promotes endometrial cancer progression through interacting with E2F1 and enhancing PKM2-mediated tumor glycolysis","authors":"Feng Geng ,&nbsp;Yanqiu Wang ,&nbsp;Guoying Cui ,&nbsp;Mingjun Fan","doi":"10.1016/j.ygyno.2025.09.008","DOIUrl":"10.1016/j.ygyno.2025.09.008","url":null,"abstract":"<div><h3>Aim</h3><div>Our purpose was to explore the effect and the potential mechanisms of tribbles pseudokinase 3 (TRIB3) on endometrial cancer (EC).</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing and the Cancer Genome Atlas (TCGA) data were used for detecting TRIB3 expression in EC. The expression of TRIB3 in human EC and para-carcinoma non-tumor tissues was examined using immunohistochemistry, qRT-PCR, and western blot. The oncogenic function of TRIB3 was verified both in vitro and in vivo. The interaction among TRIB3, E2F transcription factor 1 (E2F1) and pyruvate kinase M2 (PKM2) was studied via qRT-PCR, western blot, co-immunoprecipitation, dual luciferase reporter, immunofluorescence double staining, ubiquitination assay, and chromatin immunoprecipitation.</div></div><div><h3>Results</h3><div>TRIB3 was upregulated in EC tissues and its high expression was correlated with poor survival of patients with EC. Gain- and loss-of-function analyses showed that TRIB3 possessed strong pro-proliferative, anti-apoptotic, pro-metastatic, and pro-glucolytic capacities in EC. TRIB3 could interact with E2F1 to inhibit its degradation. The stablely expressed E2F1 acted as a transcription factor for PKM2 to enhance its expression. Rescue experiments confirmed that TRIB3 promoted EC cell malignant behavior and glycolysis via stabilizing E2F1 and enhancing PKM2 transcription. In xenograft mouse models, TRIB3 silencing inhibited EC growth and glycolysis. In addition, indapamide was identified as a compound inhibitor of TRIB3 to supress EC growth in vitro and in vitro.</div></div><div><h3>Conclusion</h3><div>TRIB3 could promote the progression of EC through interacting with E2F1 and enhancing PKM2-mediated tumor glycolysis.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 41-52"},"PeriodicalIF":4.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world utility of Silva pattern in predicting outcomes in cervical adenocarcinoma from a population-based series","authors":"Tal Milman ,&nbsp;Lien Hoang ,&nbsp;Jeremy Hamm ,&nbsp;Julia Chai ,&nbsp;Janice S. Kwon","doi":"10.1016/j.ygyno.2025.09.006","DOIUrl":"10.1016/j.ygyno.2025.09.006","url":null,"abstract":"<div><h3>Objective</h3><div>Silva pattern in cervical adenocarcinoma (AC) is associated with lymph node (LN) involvement. Utility of Silva pattern from diagnostic specimen is uncertain. Our aim was to determine concordance and outcomes for prospectively classified Silva pattern.</div></div><div><h3>Methods</h3><div>This was a single-centre retrospective study of patients with AC and assigned Silva pattern from 2018 to 2024. The primary outcome was concordance between diagnostic and surgical Silva patterns in cases treated surgically, and false negative (FN) rate of diagnostic Silva A where cases were upgraded to Silva B or C on final pathology. Secondary outcomes were LN involvement, stage, and recurrence for each pattern assessed using Fisher's Exact test.</div></div><div><h3>Results</h3><div>Of 107 patients, final Silva A, B, and C patterns were identified in 28 (26.2 %), 34 (31.8 %), and 45 (42.1 %), respectively. Among surgical cases, there was significant discrepancy between diagnostic and surgical Silva pattern (<em>p</em> = 0.004). FN rate of diagnostic Silva A was 17.6 %. LN were positive in 0, 1 (3.3 %), and 7 (15.6 %) with patterns A, B, and C (<em>p</em> = 0.032). There were 7 recurrences, including 3 with Silva B and 4 with Silva C (p = 0.032). Stage was significantly different with 0, 4 (11.8 %) and 17 (37.8 %) of Silva A, B, and C patients presenting with stage IB3-IV disease (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Discrepancy exists between diagnostic and surgical Silva patterns. Caution is advised in using diagnostic Silva pattern to guide treatment, particularly deescalating treatment in case of Silva A. Those with Silva C had significantly higher rates of advance stage, nodal involvement, and recurrences compared to Silva A and B.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 53-58"},"PeriodicalIF":4.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sacituzumab govitecan in Chinese patients with recurrent/metastatic cervical cancer: Results from the phase 2 EVER-132-003 basket study (NCT05119907)","authors":"Jusheng An ,&nbsp;Guiling Li ,&nbsp;Yunyan Zhang ,&nbsp;Mei Feng ,&nbsp;Weimin Kong ,&nbsp;Haiping Jiang ,&nbsp;Suxia Luo ,&nbsp;Wei Li ,&nbsp;Cong Xu ,&nbsp;Ling Han ,&nbsp;Yi Chen ,&nbsp;Simonetta Mocci ,&nbsp;Yilin Yan ,&nbsp;Lingying Wu","doi":"10.1016/j.ygyno.2025.09.001","DOIUrl":"10.1016/j.ygyno.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Standard treatment for metastatic cervical cancer is chemotherapy plus immunotherapy in first line and antibody-drug conjugates in second line. Limited treatment options exist after progression on first-line therapy, particularly after immunotherapy.</div></div><div><h3>Methods</h3><div>In the cervical cancer cohort of open-label, phase 2 EVER-132-003 (<span><span>NCT05119907</span><svg><path></path></svg></span>) study, Chinese patients with previously treated recurrent/metastatic cervical cancer received sacituzumab govitecan (SG) 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included investigator-assessed duration of response (DOR) and progression-free survival (PFS) as well as overall survival and safety.</div></div><div><h3>Results</h3><div>For the 40 patients enrolled, median age was 54 years. Patients received median two (range, 1–5) prior systemic treatments for recurrent/metastatic disease; 68 % received prior immunotherapy. In the full analysis set, at 9.6 months' median follow-up, ORR was 43 % (95 % CI, 27–59) and median DOR 9.2 (95 % CI, 4.6–11.7) months. Median PFS was 7.1 (95 % CI, 4.2–8.4) months. Similar efficacy was observed in patients previously treated with immunotherapy (ORR 48 %, median DOR 9.5 months). Exploratory analysis of Trop-2 expression showed limited correlation with SG efficacy. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 25 (63 %) patients, most frequently neutropenia (17 [43 %]), leukopenia (15 [38 %]), and anemia (8 [20 %]). Overall, 3 (8 %) patients discontinued SG due to TEAEs. No TEAEs led to death.</div></div><div><h3>Conclusions</h3><div>Single-agent SG demonstrated promising antitumor activity in pretreated Chinese patients with recurrent/metastatic cervical cancer and in patients previously treated with immunotherapy. AEs were manageable and consistent with known SG safety profile.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 33-40"},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and DNA methylomic factors associated with the efficacy of oral medroxyprogesterone acetate on endometrial neoplastic disease","authors":"Yuko Sugiyama ,&nbsp;Mayuko Kosugi ,&nbsp;Osamu Gotoh ,&nbsp;Akiko Tonooka ,&nbsp;Masatoshi Sano ,&nbsp;Sayuri Amino ,&nbsp;Rie Furuya ,&nbsp;Norio Tanaka ,&nbsp;Tomoko Kaneyasu ,&nbsp;Akiko Abe ,&nbsp;Mayu Yunokawa ,&nbsp;Hidetaka Nomura ,&nbsp;Yutaka Takazawa ,&nbsp;Hiroyuki Kanao ,&nbsp;Tetsuo Noda ,&nbsp;Seiichi Mori","doi":"10.1016/j.ygyno.2025.09.004","DOIUrl":"10.1016/j.ygyno.2025.09.004","url":null,"abstract":"<div><h3>Objective</h3><div>There is growing demand for fertility-sparing treatments in women with endometrial neoplastic disease who wish to conceive. Although progestins, such as medroxyprogesterone acetate (MPA), have conventionally been used for this purpose, their efficacy remains inconsistent, even when patients are selected based on clinicopathological criteria, including eligible histology or the absence of myometrial invasion or extra-uterine disease. There is thus an urgent need to identify potential biomarkers to stratify patients for improved MPA efficacy. In this study, we sought to identify candidate biomarkers associated with an efficacious response to MPA among women with endometrial disease.</div></div><div><h3>Methods</h3><div>We retrospectively conducted exome sequencing, DNA methylation microarray analysis, and hormone receptor immunohistochemistry on the samples from 62 patients with atypical endometrial hyperplasia and endometrial carcinoma, all of whom had received oral MPA treatment.</div></div><div><h3>Results</h3><div>We identified that molecular subtype, tumor mutation burden, maximal allele frequency, and DNA methylomic subtype were associated with MPA efficacy, as measured by patient response, disease recurrence, and progression-free survival. In multivariate analysis, we found independent associations of maximal allele frequency with responders (those with complete or partial remission), and of the copy-number-high subtype with shorter progression-free survival. Using region-set analyses, we also revealed that DNA methylation status of progesterone receptor-binding sites is a significant factor for distinguishing DNA methylomic subtypes for which MPA would be effective or ineffective.</div></div><div><h3>Conclusions</h3><div>These findings not only provide a foundation for identifying effective biomarkers for MPA efficacy, but also reveal deeper insights into the mechanism of action of progestins.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"202 ","pages":"Pages 24-32"},"PeriodicalIF":4.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of melanoma among people with BRCA1 and BRCA2 pathogenic variants: A systematic review and meta-analysis","authors":"Nicole M. Frontera ,&nbsp;Muhammad Danyal Ahsan ,&nbsp;Isabelle R. Chandler ,&nbsp;Sarah R. Levi ,&nbsp;Jesse T. Brewer ,&nbsp;Jessica M. Weiss ,&nbsp;Xiaoyue Ma ,&nbsp;Sarah T. Jewell ,&nbsp;Ravi N. Sharaf ,&nbsp;Melissa K. Frey","doi":"10.1016/j.ygyno.2025.08.030","DOIUrl":"10.1016/j.ygyno.2025.08.030","url":null,"abstract":"<div><h3>Background</h3><div>Patients with <em>BRCA1/2</em> pathogenic gene variants (PGVs) have an increased risk for breast, ovarian, pancreatic, and prostate cancer, with emerging evidence suggesting an association with melanoma. We aim to evaluate the strength of the melanoma association to guide cancer risk-management recommendations.</div></div><div><h3>Methods</h3><div>This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO no.: CRD42024519298). Key electronic databases were searched to identify studies evaluating the association of melanoma with germline <em>BRCA1/2</em> PGV status. Data from eligible studies were meta-analyzed.</div></div><div><h3>Results</h3><div>Thirty-nine studies were included in this review. Among 7142 patients with melanoma, the pooled prevalence of <em>BRCA1/2</em> PGVs was 1.7 % (95 % CI 1.1 % - 2.6 %). Among 2340 patients with melanoma compared to 116,501 controls, the pooled odds ratio (OR) of having a <em>BRCA1/2</em> PGV was 2.8 (95 % CI 1.5–5.4), with similar ORs for <em>BRCA1</em> (3.2 [95 % CI 1.6–6.3]) and <em>BRCA2</em> (2.8 [95 % CI 1.2–6.6]) independently. Of 14,293 <em>BRCA1/2</em> PGV carriers, 1.3 % (95 % CI 0.9–1.8) developed melanoma. The risk of melanoma among 11,154 <em>BRCA1</em> PGV carriers was not different to that among 11,553 controls (OR 1.0 [95 % CI 0.3–3.6]), with insufficient data to meta-analyze risk for <em>BRCA2</em>.</div></div><div><h3>Conclusions</h3><div>Our meta-analysis demonstrates that individuals with melanoma have a pooled OR of 2.84 for carrying a <em>BRCA1</em> or <em>BRCA2</em> PGV compared to controls; however, limited data suggest no difference in the relative risk of developing melanoma among <em>BRCA1</em> PGV carriers compared to controls, with insufficient data for relative risk with <em>BRCA2</em> PGV. These results suggest that although <em>BRCA1/2</em> PGVs may be associated with melanoma, the magnitude of increased risk is likely relatively low. Well-designed cohort studies are warranted to further investigate the magnitude of melanoma risk among <em>BRCA1/2</em> PGV carriers and providers should consider this potential risk when counseling patients.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"201 ","pages":"Pages 223-234"},"PeriodicalIF":4.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}