Anderson J, Lawton S, Thackray K
… +1 more, Kipps E
Br J Cancer
· 2026 May · PMID 41912678
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BACKGROUND: Abemaciclib plus fulvestrant was approved in Europe following publication of the MONARCH-2 trial and recommended to enter the NICE Cancer Drugs Fund for HR+/HER2- advanced breast cancer. We aimed to assess MO...BACKGROUND: Abemaciclib plus fulvestrant was approved in Europe following publication of the MONARCH-2 trial and recommended to enter the NICE Cancer Drugs Fund for HR+/HER2- advanced breast cancer. We aimed to assess MONARCH-2 generalisability to England clinical practice using real-world NHS trust data. METHODS: We identified patients receiving abemaciclib plus fulvestrant from April to December 2019 in the NHS England Blueteq and Systemic Anti-Cancer Therapy data, with follow-up to March 2024. We calculated overall survival (OS) from treatment initiation until death, and treatment-free survival (TFS) and chemotherapy-free survival (CFS) from initiation until post-discontinuation treatment or death (restricting CFS to chemotherapy). We measured outcomes using Kaplan-Meier methodology and compared to MONARCH-2. RESULTS: Median OS was 25.9 months [95% CI: 23.7, 28.4] (N = 876), compared to 46.7 months (N = 446) in MONARCH-2. Differences in gender, age and performance status did not explain OS differences. Median TFS was 11.6 months [95% CI: 10.3, 12.5] compared to a median PFS of 16.9 months in MONARCH-2. Median CFS was 15.3 months [95% CI: 13.8, 16.7], compared to 25.5 months in MONARCH-2. DISCUSSION: MONARCH-2 trial data are not generalisable to this real-world cohort, which had notably shorter OS, TFS and CFS that could not be explained by differences in measured patient characteristics.
Mavaddat N, Barnes DR, Michailidou K
… +13 more, Zhao E, Frost D, Leslie G, Dennis J, Wang Q, Bolla MK, EMBRACE, Evans DG, Tischkowitz M, Thompson DJ, Perry JRB, Antoniou AC, Easton DF
Br J Cancer
· 2026 May · PMID 41912676
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BACKGROUND: The influence of age at menarche (AAM) and age at natural menopause (ANM) on breast cancer (BC) risk in BRCA1 and BRCA2 germline pathogenic variant (PV) carriers is uncertain. Observational studies are prone...BACKGROUND: The influence of age at menarche (AAM) and age at natural menopause (ANM) on breast cancer (BC) risk in BRCA1 and BRCA2 germline pathogenic variant (PV) carriers is uncertain. Observational studies are prone to bias and have limited statistical power. Mendelian randomization (MR) minimises bias and may be used to examine causal effects. METHODS: Two-sample and age-specific MR analyses for BC were performed. For AAM, two-sample multivariable MR and mediation analyses to account for the confounding effect of body mass index (BMI), were undertaken. RESULTS: Genetic scores for ANM and AAM predicted the respective traits in PV carriers. Inverse-variance weighted hazard ratios (HR) for genetically predicted ANM per-year were HR = 0.99 (95%CI:0.97-1.01, p = 0.45) and HR = 1.04 (95% CI:1.01-1.06, p = 0.003) for BRCA1 and BRCA2 PV carriers, respectively. After adjusting for genetic associations with BMI, AAM per-year on BC risk were HR = 0.90 (95%CI:0.83-0.98, p = 0.01) and HR = 0.95 (95%CI:0.86-1.04, p = 0.26) for BRCA1 and BRCA2 carriers, respectively, consistent with a protective effect of later AAM. DISCUSSION: MR analyses support causal associations between ANM and BC risk in BRCA2, but not BRCA1, and between AAM and BC risk in BRCA1 and BRCA2 PV carriers. These results may aid risk prediction models and genetic counselling of carriers.
Cosby AG, Lebakula V, Bergene K
… +3 more, Rico Mendez G, Bumgarner M, Peluso A
Br J Cancer
· 2026 May · PMID 41912675
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BACKGROUND: After decades of increasing cancer mortality, U.S. rates declined from 1991 to 2019, a 32% decrease. we investigated rates of cancer mortality improvement across 2954 counties and selected characteristics ass...BACKGROUND: After decades of increasing cancer mortality, U.S. rates declined from 1991 to 2019, a 32% decrease. we investigated rates of cancer mortality improvement across 2954 counties and selected characteristics associated with mortality improvements. METHODS: Data was 21,381,009 county-level neoplasm deaths gleaned from death certificates via CDC WONDER. Analytical techniques included GIS and Moran's I, OLS, GWR models, and trend comparisons. RESULTS: Counties with the greatest improvement (reduction) in cancer mortality tended to be coastal, higher-income, metropolitan locations. OLS model (R = 0.65) indicated that greatest improvements were observed in counties with higher initial mortality ( ) closely followed by percent urban ( ) and median household income ( ). Whereas percent Black residents ( ), and percent with education beyond high school ( ) was less associated on outcomes. Highest income counties were the first to experience improvement in cancer mortality, the highest rates of mortality decline, and the greatest reduction in excess deaths. DISCUSSION: Even though there was significant improvement in cancer mortality nationally, there were variations in the degree of improvement linked to county location, income, and urbanisation. These results underlie the need to expand place-based initiatives designed to advance cancer health and more equitable improvements in cancer mortality outcomes.
Kwak Y, Kim TY, Lee HS
… +4 more, Nam SK, Oh HJ, Oh DY, Im SA
Br J Cancer
· 2026 May · PMID 41896652
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BACKGROUND: FGFR2b is a new emerging therapeutic target in gastric cancer (GC). This study aimed to examine the clinicopathological characteristics of FGFR2b and its relationship with key biomarkers in locally advanced (...BACKGROUND: FGFR2b is a new emerging therapeutic target in gastric cancer (GC). This study aimed to examine the clinicopathological characteristics of FGFR2b and its relationship with key biomarkers in locally advanced (LA) and metastatic or unresectable (MU) GC. METHODS: FGFR2b immunohistochemistry (IHC) (FPR2-D) positivity was defined as 2 or 3+ in any tumor cells. Additional tests included IHC for CLDN18.2 (43-14 A), HER2, PD-L1 (22C3), microsatellite instability testing, and Epstein-Barr virus ISH. RESULTS: Of the 1331 patients, 39 (2.9%) and 25 (1.9%) had FGFR2b-positive GC in any % and in ≥10% of tumor cells, respectively. A higher FGFR2b-positivity rate was significantly associated with MU GC and a shorter interval between tumor acquisition and FGFR2b testing. HER2, PD-L1, and CLDN18.2 positivity rates did not differ by FGFR2b status. Intratumoral heterogeneity was observed in 88.0% of FGFR2b-positive resected cases. FGFR2b-positive GC had a trend toward shorter overall survival regardless of clinical factors. CONCLUSION: FGFR2b positivity was higher in MU GC and in GC samples with shorter storage periods. However, no significant association was observed between FGFR2b expression and other key biomarkers or survival outcomes.
Kokts-Porietis RL, Morielli AR, Yang L
… +9 more, Matthews CE, Lupichuk S, Roldan-Urgoiti G, McNeely ML, Culos-Reed SN, Vallance JK, Dickau L, Courneya KS, Friedenreich CM
Br J Cancer
· 2026 May · PMID 41896651
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BACKGROUND: Limited research exists on how modifiable lifestyle factors influence tolerability and response to chemotherapy. We investigated the associations between health-related fitness, physical activity, and sedenta...BACKGROUND: Limited research exists on how modifiable lifestyle factors influence tolerability and response to chemotherapy. We investigated the associations between health-related fitness, physical activity, and sedentary behaviour after diagnosis with relative dose intensity (RDI) and pathologic complete response (pCR) among newly diagnosed breast cancer patients who received neoadjuvant or adjuvant chemotherapy. METHODS: This analysis includes 890 participants of the Alberta Moving Beyond Breast Cancer prospective cohort study who received chemotherapy. We directly measured cardiorespiratory fitness, muscular strength and endurance, body composition, physical activity, sedentary behaviour shortly after diagnosis and abstracted RDI and pCR data from medical charts. We used logistic regression to measure the associations with RDI ( < 85%, ≥ 85%) and pCR (no, yes). RESULTS: Of 890 participants, 726 (81.6%) achieved ≥85% RDI. We found negative linear associations between ≥ 85% RDI and greater body mass index (BMI), waist circumference, waist-to-hip ratio and fat mass percentage; and positive linear associations for greater lean body mass percentage and lean-to-fat mass ratio. We observed positive dose-response relationships between ≥ 85% RDI and relative VO, upper body and lower body strength. Higher lean-to-fat mass ratio was positively associated with pCR, in contrast to negative associations for BMI and self-reported physical activity. CONCLUSION: Greater relative aerobic fitness, muscular strength, and healthy body composition were consistently associated with better chemotherapy tolerance whereas fewer associations were found with chemotherapy response.
Kamp D, May AM, van Velzen MJM
… +6 more, Mook S, Freund JE, Mostert B, Verhoeven RHA, van Laarhoven HWM, Haj Mohammad N
Br J Cancer
· 2026 May · PMID 41888317
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BACKGROUND: Almost half of the patients with gastroesophageal cancer treated with curative intent develop recurrence. It is unknown whether the effectiveness of curative treatment is associated with the outcomes of subse...BACKGROUND: Almost half of the patients with gastroesophageal cancer treated with curative intent develop recurrence. It is unknown whether the effectiveness of curative treatment is associated with the outcomes of subsequent first-line systemic therapy. METHODS: From the Netherlands Cancer Registry, we identified patients with metachronous metastatic gastroesophageal adenocarcinoma(mGEA) initially treated for nonmetastatic disease(2015-2017) with perioperative chemotherapy or neoadjuvant chemoradiotherapy, who later received first-line systemic therapy. Effectiveness of the treatment with curative intent was assessed by time-to-treatment-failure(TTF) and by pathological response. First-line systemic therapy outcomes were assessed by TTF and overall survival(OS). Associations were analysed using Kaplan-Meier curves and multivariable Cox models. RESULTS: Patients treated with perioperative chemotherapy (n = 81) and neoadjuvant chemoradiotherapy (n = 249) with a TTF longer than the median (19.6 and 14.9 months, respectively) had significantly longer first-line TTF(HR 1.94 95% CI: 1.18-3.19; HR 1.36, 95%CI: 1.04-1.78). This also translated into longer OS for neoadjuvant chemoradiotherapy (HR 1.35 95% CI 1.03-1.77). Pathological response was not associated with systemic therapy outcomes. CONCLUSIONS: A longer TTF of curative treatment was positively associated with improved first-line systemic therapy outcomes in patients with metachronous mGEA. When counselling patients, TTF of their curative treatment may be considered, whereas pathological response may not.
Matsuda K, Ugai S, Miyahara S
… +14 more, Yao Q, Cazaubiel J, Nakazawa N, Higashioka M, Zhong Y, Chan AT, Meyerhardt JA, Ng K, Song M, Väyrynen JP, Nowak JA, Giannakis M, Ugai T, Ogino S
Br J Cancer
· 2026 May · PMID 41882312
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BACKGROUND: Given the global issue of the rising incidence of early-onset colorectal cancer (CRC), we tested the hypothesis that tumor vasculature phenotypes might vary with age at CRC diagnosis. METHOD: We used in situ...BACKGROUND: Given the global issue of the rising incidence of early-onset colorectal cancer (CRC), we tested the hypothesis that tumor vasculature phenotypes might vary with age at CRC diagnosis. METHOD: We used in situ multispectral immunofluorescence combined with digital image analysis and machine learning to measure expression of endothelial cell markers [ACKR1 (DARC), CD34, CD36, KDR (VEGFR2), LAMB1 (laminin β1), MADCAM1] and KRT (keratin) in 843 tumors derived from 4476 CRC cases in U.S.-wide prospective cohorts under the prospective cohort incident-tumor biobank method. RESULTS: Overall CD34 vessel and CD34LAMB1 vessel densities inversely correlated with younger age at CRC diagnosis (both P < 0.0001). In the inverse probability-weighted multivariable-adjusted logistic regression analyses, compared to age ≥70, odds ratios (with 95% confidence interval) for high (vs. low) overall vessel density were 0.85 (0.74-0.99) for age 55-69 and 0.63 (0.48-0.81) for age <55, and those for high (vs. low/negative) CD34LAMB1 vessel density were 0.56 (0.47-0.65) for age 55-69 and 0.28 (0.20-0.40) for age <55. CONCLUSIONS: Hypovascularities of overall and CD34LAMB1 vessels may be microenvironmental characteristics of early-onset CRC if validated by independent studies. Our findings highlight age-related tumor pathobiological differences. Identifying specific biomarkers of early-onset CRC can provide pathogenetic and etiological clues.
Crabb SJ, Morgan A, Stefanopoulou E
… +21 more, Fleure L, Griffiths GO, Boxall C, Wilding S, Nearchou T, Ewings S, Nuttall J, Eminton Z, Tilt E, Whitby E, Siu B, Ridley P, Robson L, Nobes J, Preece J, Bacon R, Martin J, Chamberlain S, Fenlon D, Hunter M, Richardson A
Br J Cancer
· 2026 May · PMID 41872531
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BACKGROUND: Androgen deprivation therapy (ADT) causes hot flushes and night sweats (HFNS) and is associated with sleep disturbance, anxiety, low mood and cognitive impairment. We tested self-help cognitive behavioural th...BACKGROUND: Androgen deprivation therapy (ADT) causes hot flushes and night sweats (HFNS) and is associated with sleep disturbance, anxiety, low mood and cognitive impairment. We tested self-help cognitive behavioural therapy (CBT), when guided by prostate cancer nurse specialist teams, for mitigation of the long-term impact of HFNS, and associated symptoms. METHODS: Prostate cancer patients receiving ADT, with a HFNS Problem Rating Scale ≥2, were randomised (1:1) to treatment as usual (TAU) or CBT + TAU, stratified by centre and treatment intent. CBT was a 4-week self-help intervention with pre- and post-intervention group workshops guided by trained prostate cancer nurse specialists. PRIMARY ENDPOINT: 6-month HFNS Problem Rating Scale. Secondary endpoints included HFNS frequency, ADT compliance and rating scales for HFNS beliefs and behaviours, quality of life, anxiety, depression and sleep. RESULTS: 162 patients were randomised. 6 month mean HFNS Problem Rating Scale score was not significantly different between the TAU and CBT + TAU groups (mean 4.08 vs 4.04, 95% confidence interval (CI) for difference: -0.89, 0.80; p = 0.97), although was improved at 6 weeks (mean 4.47 vs 3.79, 95% CI: -1.26, -0.09; p = 0.03), when depression, anxiety scores and ADT compliance also favoured CBT + TAU. CONCLUSIONS: The addition of CBT in prostate cancer patients receiving ADT improved short-term HFNS severity, in addition to improved anxiety and depression scores, but these were not maintained at 6 months. CLINICAL TRIAL REGISTRATION: ISRCTN58720120.
Sugitatsu Y, Tomida A, Suematsu M
… +5 more, Inoue T, Kubo H, Nakazawa Y, Yagyu S, Iehara T
Br J Cancer
· 2026 May · PMID 41866626
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BACKGROUND: High-risk ALK-mutant neuroblastoma (NB) presents challenges due to drug resistance and an immunosuppressive tumour microenvironment (TME). Combining molecular targeted therapy with adoptive cell therapy offer...BACKGROUND: High-risk ALK-mutant neuroblastoma (NB) presents challenges due to drug resistance and an immunosuppressive tumour microenvironment (TME). Combining molecular targeted therapy with adoptive cell therapy offers a potential therapeutic strategy. OBJECTIVE: To investigate the effects of alectinib, an ALK inhibitor, with disialoganglioside 2 (GD2) chimeric antigen receptor T (CAR-T) cell therapy in overcoming immune evasion in ALK-mutant NB. METHODS: Interferon gamma-induced programmed death-ligand 1 (PD-L1) expression and ALK signalling were analysed in ALK-mutant NB cells. The combination of alectinib and GD2 CAR-T cells was assessed in vitro, including sequential co-culture assays, and in vivo in an ALK-mutant xenograft model with multiple treatment arms. RESULTS: Alectinib suppressed PD-L1 expression by inhibiting ALK downstream pathways, including STAT3 and ERK1/2 phosphorylation. In vitro studies showed enhanced anti-tumour efficacy of GD2 CAR-T cells in combination with alectinib, with synergistic effect becoming evident in sequential coculture models. In vivo, the combination therapy reduced tumour growth, extended survival, and was associated with decreased PD-L1 expression and increased CAR-T cell infiltration. CONCLUSION: Alectinib enhances the efficacy of GD2 CAR-T therapy in ALK-mutant NB primarily by attenuating PD-L1-mediated immune evasion, supporting its potential as a combinatorial therapeutic strategy.
Huang TC, Guo JC, Lin CC
… +9 more, Kuo HY, Chuang CH, Cheng JC, Hsu FM, Lee JM, Huang PM, Liang CW, Li YI, Hsu CH
Br J Cancer
· 2026 May · PMID 41862680
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BACKGROUND: Nivolumab is effective in treating patients with esophageal squamous cell carcinoma (ESCC). The efficacy of nivolumab in combination with neoadjuvant chemoradiotherapy (CRT) remains unclear. METHODS: In this...BACKGROUND: Nivolumab is effective in treating patients with esophageal squamous cell carcinoma (ESCC). The efficacy of nivolumab in combination with neoadjuvant chemoradiotherapy (CRT) remains unclear. METHODS: In this phase II trial with Simon's 2-stage design, neoadjuvant nivolumab, paclitaxel, and cisplatin were administered with radiotherapy followed by esophagectomy to patients with locally advanced ESCC. The primary endpoint was pathological complete response (pCR). The secondary endpoints were feasibility, safety, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 17 patients were enrolled in stage I. Fourteen patients received esophagectomy, with pCR achieved in 4, below the criterion for continuing to stage II. All grade and ≥grade 3 treatment emergent adverse events (TEAEs) occurred in 15 and 4 patients, respectively. Immune-related TEAEs occurred in 7; none were ≥ grade 3. The median durations of RFS, PFS, and OS were 8, 12, and 25 months, respectively. Patients with high expression of PD-L1 had higher pCR rate (100% vs 18%, P = 0.019). CONCLUSIONS: Nivolumab in combination with neoadjuvant CRT is safe for patients with locally advanced ESCC, and may be beneficial in those with high PD-L1 expression. CLINICAL TRIAL REGISTRATION: NCT05130684.
Jabagi H, Lee JG, Yasui OW
… +2 more, Mamas MA, Sun LY
Br J Cancer
· 2026 May · PMID 41840128
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BACKGROUND: More cancer survivors are undergoing cardiac surgery, but their postoperative outcomes remain poorly understood. We aimed to describe the incidence and predictors of postoperative major adverse cardiovascular...BACKGROUND: More cancer survivors are undergoing cardiac surgery, but their postoperative outcomes remain poorly understood. We aimed to describe the incidence and predictors of postoperative major adverse cardiovascular events (MACE) and patient-defined cardiovascular and non-cardiovascular events (PACE) by cancer status. METHODS: We conducted a retrospective cohort study (2016-2022) among U.S. adults (≥18 years) undergoing cardiac surgery in MarketScan and Medicare databases. Co-primary outcomes were MACE (stroke, heart failure, myocardial infarction, repeat revascularization) and PACE (stroke, heart failure, new-onset dialysis, long-term care admission, ventilator-dependence). Cox regression evaluated the association of cancer status with postoperative outcomes. RESULTS: Among 61,581 patients (74.1% male; mean age 61 ± 10.9 years), 5381 (8.7%) had cancer. Although cancer patients exhibited higher unadjusted MACE and PACE over 2.0 ± 1.7 years (p < 0.001), multivariable analyses showed no significant association between cancer status and MACE or PACE at 30-days or at long-term follow-up MACE (aHR 1.05, 95%CI [0.99-1.10]) and PACE (aHR 1.02, [0.96-1.08]). Blood (aHR 1.13, [1.01-1.26]) and lung cancers (aHR 1.32, [1.08-1.62]) were associated with increased MACE risk, while digestive (aHR 1.17, [1.00-1.36]) and blood (aHR 1.14, [1.01-1.28]) cancers were linked to higher PACE risk. Factors more strongly predictive of PACE than MACE included older age, female sex and valvular/complex surgeries. DISCUSSION: Cancer status alone should not preclude cardiac surgery. A personalised, multidisciplinary approach may help optimise outcomes and better manage risks in this high-risk population.
Br J Cancer
· 2026 May · PMID 41832299
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BACKGROUND: Pre-clinical data demonstrated anti-tumour effect in Ewing sarcoma (ES) for zoledronic acid. This provided the rationale for the second randomisation (R2) in the EURO EWING 2012 (EE2012) trial, whether the ad...BACKGROUND: Pre-clinical data demonstrated anti-tumour effect in Ewing sarcoma (ES) for zoledronic acid. This provided the rationale for the second randomisation (R2) in the EURO EWING 2012 (EE2012) trial, whether the addition of zoledronic acid to consolidation chemotherapy improved clinical outcomes. METHODS: EE2012 was a European academic, open-label, randomised controlled phase III clinical trial. Patients with ES or Ewing-like sarcomas were included (R1). Patients meeting the R2 eligibility criteria (age 5-49 years) were randomised (1:1) to receive either nine cycles of zoledronic acid or no zoledronic acid with the R1 allocated consolidation chemotherapy. Primary and secondary outcome measures were event-free and overall survival, respectively. FINDINGS: Between 12-Aug-2014 and 20-Sep-2019, of the 640 R1 patients, 272 patients (136 in each group) were enrolled to R2. Median follow-up was 5.5 years. Three-year EFS was 59% in the zoledronic acid group and 57% in the no zoledronic acid group (adjusted hazard ratio = 0·92 (95% CI: 0·64, 1.31), p = 0.632). Three-year OS was 75% for both groups (adjusted hazard ratio = 0.84 (95% CI: 0.56, 1.25), p = 0.386). CONCLUSION: Adding zoledronic acid did not improve clinical outcomes in ES. TRIAL REGISTRATION: The trial was prospectively registered with EudraCT 2012-002107-17 and ISRCTN 54540667.
Gibson J, Carr NJ, Stanford S
… +15 more, Mirandari A, Cecil TD, Pengelly RJ, Turner S, Essex JW, Boukas K, Hocking K, Dominguez M, Mohamed F, Dayal SP, Tzivanakis A, Moran BJ, Adeleke G, Mirnezami A, Ennis S
Br J Cancer
· 2026 May · PMID 41832298
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BACKGROUND: Multicystic mesothelioma (MCM) is a rare disease and there is debate about it's neoplastic nature with a spectrum of disease behaviour and little known about the genomic profile. In contrast, the genomic prof...BACKGROUND: Multicystic mesothelioma (MCM) is a rare disease and there is debate about it's neoplastic nature with a spectrum of disease behaviour and little known about the genomic profile. In contrast, the genomic profile of malignant peritoneal mesothelioma (MPeM) is characterised. METHODS: We characterized 24 MCM and 18 MPeM cases across a panel of cancer related regions and expanded to whole-exome sequencing for 11 MCMs. Validation by amplicon sequencing and functional assessment by molecular dynamic simulation were carried out. Kaplan-Meier analysis was carried out to assess recurrence-free survival. RESULTS: Few mutations were identified in MCMs across the panel. Exome sequencing revealed 28 genes mutated in >1 MCM case. We saw significant overrepresentation of mutations in the cohesin complex in SMC3, SMC1A, and STAG3. Multiple mutations in SMC3 at codon p.E1144 indicated a mutational hotspot. Molecular dynamics simulations showed mutation at this site impacts the protein function. Amplicon sequencing confirmed hotspot mutations in further MCMs. We observed a significant association (p = 0.0302) of mutation in SMC3 or SMC1A with disease recurrence. CONCLUSIONS: We see recurrent somatic mutations in MCMs particularly at a novel mutational hotspot in SMC3, consistent with a neoplastic process. Mutations in cohesin complex genes are associated with disease recurrence.
Azam S, An A, Kensler KH
… +4 more, Weiner MG, Mount L, Bea V, Tamimi RM
Br J Cancer
· 2026 May · PMID 41832297
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BACKGROUND: Timely surgical treatment is critical for optimal breast cancer (BC) outcomes, yet delays in care persist. This study examined associations between social drivers of health (SDOH), race/ethnicity, and delayed...BACKGROUND: Timely surgical treatment is critical for optimal breast cancer (BC) outcomes, yet delays in care persist. This study examined associations between social drivers of health (SDOH), race/ethnicity, and delayed BC surgery in New York City, stratified by surgery type. METHODS: We conducted a retrospective analysis of BC cases diagnosed between 2007 and 2021 using INSIGHT Clinical Research Network data. Neighborhood-level SDOH, including household income, unemployment, percent of non-English speakers, and high school completion, were evaluated in relation to delayed surgery (>60 days from diagnosis). Multivariable logistic regression assessed associations between (1) SDOH and (2) race/ethnicity and delay of BC surgery, adjusting for confounders. RESULTS: Surgical delay occurred in 10.7% of lumpectomy and 25.3% of mastectomy patients. For lumpectomy, delays were more likely in neighborhoods with the highest non-English-speaking (OR = 1.37, 95%CI = 1.12-1.68) and higher unemployment quartiles (OR = 1.49, 95%CI = 1.22-1.82) and less likely in the highest income (OR = 0.69,95%CI = 0.56-0.84) and education quartiles (OR = 0.60, 95%CI = 0.49-0.74). Mastectomy showed similar patterns. Delays were more frequent among Non-Hispanic Black (lumpectomy OR = 2.23; mastectomy OR = 1.82) and Hispanic patients (OR = 1.64; OR = 1.39). CONCLUSION: This large, multi-institutional study reveals persistent disparities in timely surgical care. Nearly 15% experienced delays, with higher odds among Non-Hispanic Black, Hispanic, and socioeconomically disadvantaged patients, underscoring the need for equity-focused interventions.
Mitchell AR, Chen Y, Pugliese G
… +4 more, Vino Flores G, Davies DM, Maher J, Wells CM
Br J Cancer
· 2026 May · PMID 41792510
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BACKGROUND: P-21 activated kinase (PAK) overexpression, phosphorylation, and gene amplification have been reported to increase cellular invasion in ovarian cancer (ovcan), worsening patient prognoses. One notable method...BACKGROUND: P-21 activated kinase (PAK) overexpression, phosphorylation, and gene amplification have been reported to increase cellular invasion in ovarian cancer (ovcan), worsening patient prognoses. One notable method of ovcan survival is through the PD-(L)1 checkpoint pathway, and PD-L1 expression in ovcan is correlated with poor patient outcomes. However, PD-1 and PD-L1 targeted clinical trials in ovcan have shown modest results. This work has examined the possibility of using PAKi and PD-1 blockade as a combination therapy. METHODS: PAK and PD-L1 expression in ovarian cells was determined. A novel 3D spheroid assay was used to assess ovcan invasion. Ovcan cell viability, downstream pathway signalling, and surface PD-L1 expression were evaluated after treatment with PAK inhibitors and co-culture with cytotoxic CD8 T cells. Ovcan cell and CD8 T cell co-cultures were treated with a combination of PAK inhibition and PD-1 checkpoint blockade and ovcan cell viability was assessed. RESULTS: Ovcan cells showed significant sensitivity to PAKi. CD8 T cell killing of ovcan cells improved following pre-treatment with PAK inhibitors, and this was further augmented with PD-1 blockade. DISCUSSION: The work presented here demonstrates the efficacy of PAK inhibition and PD-1 checkpoint blockade as a combination therapy for high-grade serous ovarian cancer.