European Journal of Cancer最新文献

{"title":"Differences in immunogenicity of TP53-mutated cancers with low tumor mutational burden (TMB) A study on TP53mut endometrial-, ovarian- and triple-negative breast cancer","authors":"Katharina Steger ,&nbsp;Heidelinde Fiegl ,&nbsp;Barin Feroz ,&nbsp;Katharina Leitner ,&nbsp;Christian Marth ,&nbsp;Hubert Hackl ,&nbsp;Alain G. Zeimet","doi":"10.1016/j.ejca.2025.115320","DOIUrl":"10.1016/j.ejca.2025.115320","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore why in large phase III randomized clinical trials <em>TP53</em>-mutated (<em>TP53</em>mut) endometrial cancer (EC) was the only tumor showing survival benefit to immune checkpoint inhibitors (ICIs) added to chemotherapy when compared with other low TMB <em>TP53</em>mut cancers, such as high-grade serous ovarian (HGSOC) and triple-negative breast cancer (TNBC).</div></div><div><h3>Experimental Design</h3><div>From 606 patients with one of the three mentioned cancers, “The Cancer Genome Atlas” data on clinical outcome, TMB and detailed composition of the tumor immune-microenvironment (TIME) (immune infiltrating cells, cytokines, and other immune-modulators) were compared using the Kruskal-Wallis test, followed by Pearson correlation. Prognostic value of studied variables was assessed by Kaplan-Meier and Cox-regression analyses.</div></div><div><h3>Results</h3><div>TMB was very low in all three <em>TP53</em>mut entities, being lowest in EC (median: 1.27 Mut/Mb; p &lt; 0.001). Interestingly, high TMB was significantly associated with improved clinical outcome in every entity, whereby best discrimination for PFS was found in EC (HR: 0.52). Compared to EC, immune-suppressing regulatory T-cells were higher in HGSOC and TNBC (p &lt; 0.001) and M2-like macrophages higher in HGSOC (p &lt; 0.001). In contrast, immune-activating mDCs were more prominent in EC than in HGSOC (p &lt; 0.001). Differential modulator expression analyses revealed highest discrimination for the immune-inhibiting <em>FOXP3</em>, <em>C1QA</em> and <em>XBP1</em>, which all exhibited lower levels in EC compared with HGSOC and TNBC (p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Characteristics of TIME differ substantially among the assessed entities in terms that EC exhibits fewer immunosuppressive traits, expecting a higher likelihood for responding to ICIs, despite a very low TMB, whereas HGSOC and TNBC exhibit an immune hostile TIME.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115320"},"PeriodicalIF":7.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exceptional responses to systemic treatment in metastatic breast cancer: clinical features and long-term outcomes","authors":"Gaia Griguolo ,&nbsp;Michele Bottosso ,&nbsp;Andrea Crema ,&nbsp;Tommaso Giarratano ,&nbsp;Federica Miglietta ,&nbsp;Giorgio Bonomi ,&nbsp;Eleonora Mioranza ,&nbsp;Davide Napetti ,&nbsp;Davide Massa ,&nbsp;Giovanni Faggioni ,&nbsp;Maria Vittoria Dieci ,&nbsp;Valentina Guarneri","doi":"10.1016/j.ejca.2025.115321","DOIUrl":"10.1016/j.ejca.2025.115321","url":null,"abstract":"<div><h3>Background</h3><div>Interest in metastatic solid tumors patients achieving exceptionally durable responses to systemic treatment is progressively increasing; however, available evidence still remains limited. This study characterizes patients with metastatic breast cancer (mBC) achieving an exceptional response, with a focus on patients discontinuing systemic treatment.</div></div><div><h3>Methods</h3><div>In this retrospective monocentric study, patients with mBC achieving exceptional responses (2021–2023) were identified; clinical features, hormone receptor (HR) and HER2 status, and radiological responses were collected. Exceptional response was defined as complete (CR) or partial response (PR) lasting for more than twice the expected progression-free survival (PFS). No evidence of disease (NED) was defined as radiological absence of disease achieved integrating locoregional treatments.</div></div><div><h3>Results</h3><div>We identified 58 exceptional responders: 31 HER2+ (53.5 %), 16 HR+ /HER2- (27.6 %), and 11 HR-/HER2- (19.0 %). 5-year PFS was 89.1 % and 5-year OS was 94.6 % overall, and numerically better in HR-/HER2- mBC (5-year PFS/OS: 100 %) compared to HER2+ (90.2 %/93.5 %) and HR+ /HER2- (80.8 %/93.8 %) mBC.</div><div>Best radiological response was CR/NED in 69.0 % and PR in 31.0 % of patients. CR/NED status was significantly associated with better outcomes compared to PR (5-year OS: 100 % vs. 83.0 %, p = 0.004). Eleven patients (9 with CR/NED, 2 with PR) discontinued treatment in absence of disease progression; subsequent progression was observed only in one patient with PR.</div></div><div><h3>Conclusion</h3><div>mBC patients achieving exceptional responses exhibit favorable long-term survival outcomes, particularly if achieving CR/NED. These findings highlight the importance of further research to refine management strategies and explore the potential for systemic treatment discontinuation in these patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115321"},"PeriodicalIF":7.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Tumour microenvironment changes after osimertinib treatment resistance in non-small cell lung cancer” [Eur J Cancer 189 (2023) 112919]","authors":"Ruoshuang Han ,&nbsp;Haoyue Guo ,&nbsp;Jinpeng Shi ,&nbsp;Haowei Wang ,&nbsp;Sha Zhao ,&nbsp;Yijun Jia ,&nbsp;Xiaozhen Liu ,&nbsp;Jiayu Li ,&nbsp;Lei Cheng ,&nbsp;Chao Zhao ,&nbsp;Xuefei Li ,&nbsp;Caicun Zhou","doi":"10.1016/j.ejca.2025.115307","DOIUrl":"10.1016/j.ejca.2025.115307","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115307"},"PeriodicalIF":7.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Feasibility of AI as first reader in the 4-IN-THE-LUNG-RUN lung cancer screening trial: Impact on negative-misclassifications and clinical referral rate, European Journal of Cancer, Volume 216, 5 February 2025, 115214","authors":"Anna N.H. Walstra ,&nbsp;Harriet L. Lancaster ,&nbsp;Marjolein A. Heuvelmans ,&nbsp;Carlijn M. van der Aalst ,&nbsp;Juul Hubert ,&nbsp;Dana Moldovanu ,&nbsp;Sytse F. Oudkerk ,&nbsp;Daiwei Han ,&nbsp;Jan Willem C. Gratama ,&nbsp;Mario Silva ,&nbsp;Harry J. de Koning ,&nbsp;Matthijs Oudkerk","doi":"10.1016/j.ejca.2025.115294","DOIUrl":"10.1016/j.ejca.2025.115294","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115294"},"PeriodicalIF":7.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Treating Fields therapy in platinum-resistant ovarian cancer: Results of the ENGOT-ov50/GOG-3029/INNOVATE-3 pivotal phase 3 randomized study","authors":"Ignace Vergote ,&nbsp;Larry J. Copeland ,&nbsp;Toon Van Gorp ,&nbsp;Annouschka Laenen ,&nbsp;Giovanni Scambia ,&nbsp;Premal H. Thaker ,&nbsp;David Cibula ,&nbsp;Nicoletta Colombo ,&nbsp;Jayanthi Lea ,&nbsp;Antonio Gonzalez-Martin ,&nbsp;Jacob Korach ,&nbsp;Jalid Sehouli ,&nbsp;Bradley J. Monk ,&nbsp;Viola Heinzelmann-Schwarz ,&nbsp;Regina Berger ,&nbsp;Joseph Buscema ,&nbsp;Susie Lau ,&nbsp;Radoslaw Mądry ,&nbsp;Hannelore Denys ,&nbsp;Jessica Thomes Pepin ,&nbsp;David M. O’Malley","doi":"10.1016/j.ejca.2025.115306","DOIUrl":"10.1016/j.ejca.2025.115306","url":null,"abstract":"<div><h3>Purpose</h3><div>Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC).</div></div><div><h3>Patients and methods</h3><div>Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0–1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m² weekly) or PTX. Primary endpoint was overall survival (OS). Exploratory post-hoc analyses assessed OS in pegylated liposomal doxorubicin (PLD)-naive patients.</div></div><div><h3>Results</h3><div>Between March 2019 and November 2021, 558 patients (ECOG PS 0, 60.2 %; median [range] age, 62 [22–91] years) were assigned TTFields+PTX (n = 280) or PTX (n = 278). 24.4 % had 4 + prior LOT. Median OS was 12.2 months with TTFields+PTX vs 11.9 months with PTX (HR, 1.01; 95 % CI, 0.83–1.24; p = 0.89). Grade ≥ 3 adverse events (AEs) were similar between treatment groups. Grade 1/2 device-related skin AEs occurred in 83.6 % of patients receiving TTFields therapy. In exploratory post-hoc analysis in PLD-naive patients, median OS was 16 months with TTFields+PTX (n = 113) vs 11.7 months with PTX (n = 88; nominal HR, 0.67; 95 % CI, 0.49–0.94; p = 0.03).</div></div><div><h3>Conclusions</h3><div>No new safety signals were identified. TTFields+PTX did not significantly improve OS compared with PTX in the intent-to-treat population. An exploratory post-hoc analysis suggests a potentially favorable benefit-risk profile for TTFields therapy in PLD-naive patients.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115306"},"PeriodicalIF":7.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tegafur-uracil maintenance chemotherapy post-chemoradiotherapy for cervical cancer: Randomized trial","authors":"Kosei Hasegawa ,&nbsp;Shin Nishio ,&nbsp;Kouji Yamamoto ,&nbsp;Hiroyuki Fujiwara ,&nbsp;Hiroya Itagaki ,&nbsp;Tomonori Nagai ,&nbsp;Hirokuni Takano ,&nbsp;Satoshi Yamaguchi ,&nbsp;Akiko Kudoh ,&nbsp;Yurina Suzuki ,&nbsp;Tomoko Nakamoto ,&nbsp;Akira Kurosaki ,&nbsp;Masaaki Kamio ,&nbsp;Kazuyoshi Kato ,&nbsp;Kazuto Nakamura ,&nbsp;Kazuhiro Takehara ,&nbsp;Hideaki Yahata ,&nbsp;Hiroaki Kobayashi ,&nbsp;Motoaki Saito ,&nbsp;Keiichi Fujiwara","doi":"10.1016/j.ejca.2025.115304","DOIUrl":"10.1016/j.ejca.2025.115304","url":null,"abstract":"<div><h3>Aim</h3><div>Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC.</div></div><div><h3>Methods</h3><div>Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300–400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints.</div></div><div><h3>Results</h3><div>Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, <em>P</em> = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, <em>P</em> = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS.</div></div><div><h3>Conclusions</h3><div>These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115304"},"PeriodicalIF":7.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population-based evidence on treatment-volume and outcome association supports concentration of multidisciplinary care for patients with head and neck cancer in Belgium","authors":"Hanne Peirelinck,&nbsp;Cindy De Gendt,&nbsp;Olivier Lenssen,&nbsp;Sandra Nuyts,&nbsp;Liesbet Van Eycken","doi":"10.1016/j.ejca.2025.115300","DOIUrl":"10.1016/j.ejca.2025.115300","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115300"},"PeriodicalIF":7.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation and development of a refined M1 category for nasopharyngeal carcinoma based on the version-nine of AJCC/UICC TNM staging system in the immunotherapy era: A multicenter cohort study","authors":"Hanchuan Xu ,&nbsp;Yujun Hu ,&nbsp;Tao Xie ,&nbsp;Lihu Lu ,&nbsp;Zhiwei Yan ,&nbsp;Xinlan Chen ,&nbsp;Lili Zhu ,&nbsp;Chuanmiao Xie ,&nbsp;Tianzhu Lu ,&nbsp;Jingao Li ,&nbsp;Jianji Pan ,&nbsp;Shaojun Lin ,&nbsp;Xiaochang Gong ,&nbsp;Qiaojuan Guo","doi":"10.1016/j.ejca.2025.115305","DOIUrl":"10.1016/j.ejca.2025.115305","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the applicability of the M1 category of the version-nine of AJCC/UICC TNM staging system (TNM-9) for M1 nasopharyngeal carcinoma (M1-NPC) in immunotherapy era and propose potential refinements.</div></div><div><h3>Methods</h3><div>M1-NPC patients who underwent palliative chemotherapy and immune checkpoint inhibitors (ICIs) between January 2019 and June 2023 across five institutions were included and re-staged according to TNM-9. Overall survival (OS) and Progression-free survival (PFS) were analyzed. A recursive partitioning analysis (RPA) model was employed to derive a new RPA-M1 category.</div></div><div><h3>Results</h3><div>Among the 472 patients included, 219 were M1a and 253 were M1b. With a median follow-up time of 27 months, the M1a subgroup exhibited significantly higher 2-year OS (90.4 % vs. 73.7 %) and PFS (69.2 % vs. 40.6 %) than M1b subgroup (all <em>P</em>&lt;0.001), which was further confirmed by multivariate analysis (MVA). Additionally, number of involved organs was found to be another independent predictor. New RPA-M1 category were then developed: RPA-M1a (≤3 metastatic lesions and confined to one single organ), RPA-M1b (≤3 metastatic lesions but involving multiple organs or &gt;3 lesions and confined to one single organ), and RPA-M1c (patients with &gt;3 metastatic lesions and involving multiple organs), with 2-year OS rates of 91.5 %, 81.4 %, and 69.8 %, respectively (<em>P</em> &lt; 0.05) and PFS rates of 72.4 %, 54.3 % and 29.1 %, respectively (<em>P</em> &lt; 0.005). Compared to the M1 Category in TNM-9, RPA-M1 category had a lower Akaike Information Criterion (AIC) and a higher concordance index (C-index) for OS and PFS.</div></div><div><h3>Conclusion</h3><div>The M1 category in the TNM-9 is applicable in the immunotherapy era. The RPA-M1 category offers improve depiction of survival outcomes compared to TNM-9, allowing for more refined stratification of patient outcomes and individulized decision-tailoring.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115305"},"PeriodicalIF":7.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four decades of lung cancer: Trends in comorbidities and causes of death in a nationwide Danish cohort","authors":"Morten Borg ,&nbsp;Anders Løkke ,&nbsp;Rikke Ibsen ,&nbsp;Ole Hilberg","doi":"10.1016/j.ejca.2025.115303","DOIUrl":"10.1016/j.ejca.2025.115303","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer remains the leading cause of cancer-related deaths globally, with gradual improvements in patient survival attributed to early detection through low-dose computed tomography screening and advances in oncological therapies. Despite these advancements, the management of comorbidities, particularly cardiovascular disease and chronic obstructive pulmonary disease, is critical due to their shared causal link with lung cancer - smoking. This study explores the prevalence of comorbidities among lung cancer patients in Denmark over four decades, using comprehensive national registry data.</div></div><div><h3>Methods</h3><div>By examining the Danish National Patient Register and Danish Cancer Registry, we identified all Danish lung cancer cases diagnosed from 1980 to 2018, analyzing comorbidities and causes of death. A comparison cohort matched by age, sex, municipality, and marital status was also established.</div></div><div><h3>Findings</h3><div>The findings reveal a significant increase in comorbidities among lung cancer patients over time, while this increase was less significant in the comparison cohort. Almost half of lung cancer patients had at least one comorbidity in the most recent period, 2008–2018. Cardiovascular disease, chronic obstructive pulmonary disease, diabetes, stroke, and peripheral atherosclerosis were the most prevalent comorbidities. Among patients diagnosed with lung cancer, it was the cause of death in 84 % of cases. The study also highlights a notable decrease in deaths from ischemic heart disease, with an increase in dementia-related deaths, suggesting an increasing burden of neurodegenerative diseases in aging populations.</div></div><div><h3>Interpretation</h3><div>This longitudinal analysis highlights that as the burden of comorbidities increases, comprehensive management strategies become increasingly crucial. These strategies could include less invasive diagnostic approaches, such as endobronchial evaluation, as well as treatment options like segmental resection and stereotactic body radiation. Addressing comorbidities alongside cancer treatment may improve patient outcomes and overall quality of life in aging populations.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115303"},"PeriodicalIF":7.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic BRCA1/2 mutations are associated with a similar survival advantage to their germline counterparts in tubo-ovarian high grade serous carcinoma","authors":"Robert L. Hollis ,&nbsp;Michael Churchman ,&nbsp;Graeme R. Grimes ,&nbsp;Alison M. Meynert ,&nbsp;Philippe Gautier ,&nbsp;Lynn McMahon ,&nbsp;Kitty Sherwood ,&nbsp;Ailsa J. Oswald ,&nbsp;Ian Croy ,&nbsp;Michelle Ferguson ,&nbsp;Cameron W. Martin ,&nbsp;Trevor McGoldrick ,&nbsp;Neil McPhail ,&nbsp;Helen Creedon ,&nbsp;J. Carl Barrett ,&nbsp;Ruth March ,&nbsp;Brian A. Dougherty ,&nbsp;Patricia Roxburgh ,&nbsp;Ailith Ewing ,&nbsp;C. Simon Herrington ,&nbsp;Charlie Gourley","doi":"10.1016/j.ejca.2025.115299","DOIUrl":"10.1016/j.ejca.2025.115299","url":null,"abstract":"<div><h3>Background</h3><div>Half of high grade serous tubo-ovarian carcinomas (HGSOC) demonstrate homologous recombination repair (HRR) deficiency, most commonly through germline or somatic pathogenic variants in <em>BRCA1</em>/<em>2</em> (g<em>BRCA1</em>/<em>2</em> or s<em>BRCA1</em>/<em>2</em>). g<em>BRCA1</em>/<em>2</em> is associated with favourable survival, greater response rate to platinum-based chemotherapy, and marked sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. s<em>BRCA1</em>/<em>2</em> has been assumed to confer a similar clinical phenotype; however, few studies have specifically investigated s<em>BRCA1</em>/<em>2</em> versus g<em>BRCA1</em>/<em>2</em> to demonstrate their equivalence.</div></div><div><h3>Methods</h3><div>We investigated the association of g<em>BRCA1</em>/<em>2</em>, s<em>BRCA1</em>/<em>2</em> and non-<em>BRCA</em> HRR gene mutations with HGSOC patient survival using two patient cohorts (cohort 1, n = 174 matched FFPE tumour and normal with panel-based sequencing; cohort 2, n = 279 matched fresh tumour and normal with whole genome sequencing). TCGA-OV samples (n = 316) were used for external validation.</div></div><div><h3>Results</h3><div>Patients with HRR-mutant tumours (<em>BRCA1</em>, <em>BRCA2</em>, non-<em>BRCA</em> HRR-mutant) demonstrated prolonged survival across both cohorts (cohort 1: multivariable hazard ratio [multiHR] 0.53 [0.32–0.87]; cohort 2: multiHR 0.36 [0.25–0.51]). g<em>BRCA1</em>/<em>2</em> and s<em>BRCA1</em>/<em>2</em> were associated with a similar survival benefit compared to the HRR-wildtype group in the combined cohort (cohort 1 +2) (g<em>BRCA1</em>/<em>2</em>: multiHR 0.50 [0.34–0.71]; s<em>BRCA1</em>/<em>2</em>: multiHR 0.41 [0.25–0.68]). These findings were recapitulated using the TCGA-OV dataset (g<em>BRCA1</em>/<em>2</em>: multiHR 0.56 [0.34–0.91]; s<em>BRCA1</em>/<em>2</em>: multiHR 0.48 [0.25–0.92]). Non-<em>BRCA</em> HRR mutations were associated with marked survival advantage (multiHR vs HRR-wildtype 0.22 [0.11–0.45]). The survival advantage in <em>BRCA1</em>-mutant cases (germline or somatic) was less marked (multiHR for non-<em>BRCA</em> HRR-mutant vs <em>BRCA1</em>-mutant 0.41 [0.19–0.90]). g<em>BRCA1</em>/<em>2</em>, s<em>BRCA1</em>/<em>2</em> and non-<em>BRCA</em> HRR mutations were all associated with high HRDetect scores measuring HRR deficiency (median 1.00 versus 0.56 in HRR-wildtype, P &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>g<em>BRCA1</em>/<em>2</em> and s<em>BRCA1</em>/<em>2</em> are equivalent in their association with prolonged survival. Non-<em>BRCA</em> HRR gene mutations may be associated with markedly favourable survival in HGSOC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"219 ","pages":"Article 115299"},"PeriodicalIF":7.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}