bims-ovdlit 2026-01-11 papers

bims-ovdlit

Biomed News

on Ovarian cancer: early diagnosis, liquid biopsy and therapy

Issue of 2026–01–11
twelve papers selected by
Lara Paracchini, Humanitas Research

ESMO Congress 2025.
Circulating tumor DNA in ovarian cancer diagnosis: from signal to standard.
Risk reduction bilateral salpingo-oophorectomy with vNOTES: A new era in cancer prevention strategies.
Artificial Intelligence for Genetic Cancer Risk Assessment in Gynecologic Oncology: A Review of the Current Landscape and Future Directions.
Ancestral diversity in complex disease genetics: from discovery to translation.
Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants.
Risk-Reducing Bilateral Mastectomy and Mortality in Carriers of BRCA1 and BRCA2 Variants: A Systematic Review and Meta-Analysis.
A guide to cancer screening.
Ovarian cancer: Age based blood test thresholds proposed to improve diagnosis.
When the time is right.
Insights from three decades of BRCA1/2 modeling in mice.
Clinical utility of longitudinal ctDNA monitoring by multiplex MS-ddPCR for risk stratification and follow-up in rectal cancer.

EClinicalMedicine. 2025 Dec;90 103650

ESMO Congress 2025.

DOI: https://doi.org/10.1016/j.eclinm.2025.103650
Int J Gynecol Cancer. 2026 Jan;pii: S1048-891X(25)01982-6. [Epub ahead of print]36(1): 102858

Circulating tumor DNA in ovarian cancer diagnosis: from signal to standard.

Behrouz Zand.



Keywords:  Circulating Tumor DNA; DNA Methylation; Early Detection; Liquid Biopsy; Ovarian Cancer

DOI:  https://doi.org/10.1016/j.ijgc.2025.102858
Surg Oncol. 2026 Jan 02. pii: S0960-7404(25)00164-1. [Epub ahead of print]64 102349

Risk reduction bilateral salpingo-oophorectomy with vNOTES: A new era in cancer prevention strategies.

Maria Pellisé-Tintoré, Thomas Gaillard, Enora Laas, Virginie Fourchotte, Hélène Didelot, Lea Pauly, Jean Guillaume Feron, Fabien Reyal, Fabrice Lecuru.

   INTRODUCTION: Women with BRCA1 and BRCA2 mutations face a significantly increased lifetime risk of developing ovarian and fallopian tube cancer. Minimally invasive techniques are the gold standard access to perform risk-reduction operations. This study aims to evaluate the feasibility and safety of prophylactic bilateral salpingo-oophorectomy using the vaginal natural orifice transluminal endoscopic surgery (vNOTES) technique as a risk-reduction strategy.
MATERIAL AND METHODS: A prospective study was conducted between October 2023 and December 2024, involving 25 high-risk women at an international, university-affiliated cancer center. All patients underwent prophylactic bilateral salpingo-oophorectomy via transvaginal access using vNOTES. Key data collected included age, BMI, operative time, and blood loss, with primary outcomes focusing on feasibility, complications, and recovery.
RESULTS: Twenty-five BRCA-mutated patients underwent prophylactic bilateral adnexectomy via vNOTES. Median age was 48 years (range 41-59) and median BMI 24.1 kg/m2 (range 19.1-30.4). All procedures were completed without conversion to laparoscopy or laparotomy, and vNOTES enabled full abdominal exploration. Median operative time was 40 min (IQR 32-44), with minimal blood loss (<100 mL in 96 %) and no intraoperative complications. Postoperative recovery was uneventful, with no pain reported and 96 % of patients discharged the same day. No late complications related to the surgical technique were observed.
CONCLUSION: Prophylactic bilateral salpingo-oophorectomy using the vNOTES technique appears to be a feasible and safe option for reducing the risk of ovarian and fallopian tube cancers in high-risk women. Further studies with larger cohorts are needed to validate these findings.

Keywords:  Minimally invasive surgical procedures; Risk-reduction strategy; Salpingo-oophorectomy; vNOTES

DOI:  https://doi.org/10.1016/j.suronc.2025.102349
Clin Obstet Gynecol. 2026 Jan 06.

Artificial Intelligence for Genetic Cancer Risk Assessment in Gynecologic Oncology: A Review of the Current Landscape and Future Directions.

Roxanna Haghighat, Sarah R Levi, Melissa K Frey.

  Hereditary cancer syndromes are associated with up to 25% of ovarian and 5% of endometrial cancers, yet rates of genetic testing and counseling remain low. Artificial intelligence (AI) offers new opportunities to streamline risk assessment, enhance gene variant interpretation, and expand access to genetic counseling. This narrative review synthesizes current evidence on AI applications in gynecologic cancer genetic risk assessment, including chatbot-based risk assessment, natural language processing of electronic records, and machine-learning approaches to variant classification. We highlight key challenges, including data bias, privacy, and implementation barriers, and outline future directions for AI technologies in gynecologic cancer genetic risk assessment.

Keywords:  artificial intelligence; cancer; genetics; gynecologic oncology; hereditary breast and ovarian cancer; risk screening

DOI:  https://doi.org/10.1097/GRF.0000000000000996
Nat Rev Genet. 2026 Jan 06.

Ancestral diversity in complex disease genetics: from discovery to translation.

Karoline Kuchenbaecker, Georgina Navoly.

The expansion of ancestrally diverse genetic cohorts has altered the landscape of complex disease genetics. Differences in linkage disequilibrium across populations have improved fine-mapping and the identification of target genes - key steps for translating findings from genome-wide association studies into biological understanding. Whilst there is widespread sharing of genetic architecture across ancestries, loci that display heterogeneity in causal genetic effects across populations can offer unique biological insights. Here, we review how ancestral and global diversity shape genetic discoveries. As we advance towards global precision medicine, integrating genomic data with diverse environmental and social factors will be crucial to account for population-specific contexts that can influence disease risk or treatment response.

DOI: https://doi.org/10.1038/s41576-025-00921-3
World J Oncol. 2026 Feb;17(1): 14-24

Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants.

Hikmat Abdel-Razeq, Razan Mansour.

  Breast cancer remains the most common cancer globally, with approximately 5-15% of cases linked to pathogenic variants primarily in BRCA1 or BRCA2. These mutations greatly increase cancer risks, highlighting the critical need for more effective screening and prevention strategies. This review aimed to summarize existing evidence and propose a comprehensive approach to reducing cancer risk in unaffected mutation carriers. A narrative review of published literature was conducted to evaluate risk-reduction strategies, including surveillance, enhanced imaging, risk-reducing surgeries, and chemoprevention. Barriers to the uptake of these strategies and the psychological impact on carriers were also examined. Annual magnetic resonance imaging (MRI) remains the most sensitive screening tool for early breast cancer detection in high-risk individuals. Selective estrogen receptor modulators (SERMs) and aromatase inhibitors have shown potential as chemopreventive agents, but uptake remains limited due to concerns about efficacy and side effects. Risk-reducing surgeries, such as bilateral salpingo-oophorectomy (BSO) and mastectomy, significantly lower the risk of breast and ovarian cancer; however, their uptake is often hindered by emotional, cultural, and financial factors. Family communication of genetic results and support by healthcare professionals are critical to encouraging preventive actions. Effective screening and risk-reduction strategies are available for BRCA1 and BRCA2 carriers, yet barriers to implementation persist. Personalized counseling, enhanced accessibility, and culturally sensitive education are essential to improving the adoption of these preventive measures. Further studies are needed to explore novel chemoprevention options and interventions to address the unmet needs of carriers worldwide.

Keywords:  BRCA1; BRCA2; BSO; Carrier; Germline genetic testing; Oophorectomy; Prophylactic mastectomy; Risk-reducing surgery

DOI:  https://doi.org/10.14740/wjon2692
JAMA Surg. 2026 Jan 07.

Risk-Reducing Bilateral Mastectomy and Mortality in Carriers of BRCA1 and BRCA2 Variants: A Systematic Review and Meta-Analysis.

Cathal O'Reilly, Jennifer L McGarry, Alexandra M Zaborowski, Matthew G Davey, Denis Evoy, Jane Rothwell, Damian McCartan, Claire L Rutherford, Michael R Boland, Ruth S Prichard.

Importance: Risk-reducing bilateral mastectomy reduces the incidence of breast cancer in female carriers of the BRCA pathogenic variants, but its association with mortality remains uncertain.
Objective: To evaluate the association between risk-reducing bilateral mastectomy and overall and breast cancer-specific mortality in female carriers of BRCA pathogenic variants.
Data Sources: PubMed, Scopus, CINAHL, Embase, and CENTRAL were searched in May 2025, with English-language restriction and no date limit. Reference lists of included studies and relevant reviews were also examined.
Study Selection: Eligible studies compared female carriers of BRCA1 and BRCA2 pathogenic variants who underwent risk-reducing bilateral mastectomy with those who did not and reported overall mortality or breast cancer-specific mortality. Studies including patients with a history of breast cancer were excluded.
Data Extraction and Synthesis: This meta-analysis followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Two authors independently performed study selection, data extraction, and risk of bias assessment (using Risk of Bias in Nonrandomized Studies-of Interventions, version 2). Odds ratios (ORs) and hazard ratios (HRs) were pooled using fixed- and random-effects models according to methodological assessment.
Main Outcomes and Measures: Overall and breast cancer-specific mortality.
Results: Six observational studies met the inclusion criteria, comprising 6135 carriers of the BRCA1 or BRCA2 variant. Weighted median age at inclusion was 38.0 years, with reported age ranges spanning 15.3 to 85.3 years. Risk-reducing bilateral mastectomy was associated with lower overall mortality in both unadjusted (OR, 0.38; 95% CI, 0.27-0.55; P < .001) and adjusted (HR, 0.37; 95% CI, 0.23-0.60; P < .001) analyses. Breast cancer-specific mortality was also reduced (OR, 0.19; 95% CI, 0.08-0.47; P < .001; HR, 0.14; 95% CI, 0.04-0.49; P = .002).
Conclusions and Relevance: Risk-reducing bilateral mastectomy was associated with lower overall and breast cancer-specific mortality in carriers of the BRCA variants. These findings support the role of risk-reducing bilateral mastectomy as a potentially life-extending intervention and may inform the shared decision-making discussions in these women.

DOI: https://doi.org/10.1001/jamasurg.2025.5929
Nat Rev Clin Oncol. 2026 Jan 07.

A guide to cancer screening.

Stephen W Duffy, Judith Offman.

The aim of cancer screening is to identify pre-malignant conditions, which can be removed or treated, or earlier-stage disease, for which treatment is more likely to be curative, in non-symptomatic individuals. Currently, screening programmes are being consolidated for five cancer types (breast, prostate, cervical, colorectal and lung) and several other cancer types are the focus of specific initiatives. Cancer screening is at a point of potential major transformation owing to technological advances in detection. In this Review, we first recapitulate the general principles of cancer screening. We then provide a timely overview of the current screening practices for breast, cervical, colorectal, prostate and lung cancer, addressing major challenges and potential future changes in practice. We also discuss other malignancies for which screening initiatives might be worth considering. Finally, we highlight technological developments in cancer detection that might hold promise for screening an increasing number of cancers in the future, notably some that reflect unmet needs.

DOI: https://doi.org/10.1038/s41571-025-01112-z
BMJ. 2026 Jan 06. 392 s23

Ovarian cancer: Age based blood test thresholds proposed to improve diagnosis.

Jacqui Wise.

DOI: https://doi.org/10.1136/bmj.s23
Nat Rev Cancer. 2026 Jan 09.

When the time is right.

Daniela Senft.

DOI: https://doi.org/10.1038/s41568-025-00904-w
Nat Genet. 2026 Jan 06.

Insights from three decades of BRCA1/2 modeling in mice.

Julia-Star Darnold, Jos Jonkers.

Since the discovery of the BRCA1 and BRCA2 (hereafter referred to as BRCA1/2) hereditary breast and ovarian cancer genes three decades ago, genetically engineered and patient-derived mouse models have been instrumental in advancing our understanding of BRCA1/2 biology, particularly their roles in normal development, tumor suppression and therapy response. Brca1/2-mutant mouse models and derivative cell lines have facilitated in vivo dissection of BRCA1/2 functions and identification of the cellular origin and (epi)genetic drivers of BRCA1/2-associated cancer. Genetically engineered and patient-derived mouse tumor models have also been instrumental in developing new (combination) therapies for patients with BRCA1/2-mutated cancers and to study mechanisms of therapy resistance. In this Perspective, we highlight the crucial insights into the complex biology of BRCA1/2 these models have afforded and emphasize those aspects that remain to be elucidated. We also propose next-generation mouse models to further advance our understanding of BRCA1/2 and improve the quality of life of mutation carriers.

DOI: https://doi.org/10.1038/s41588-025-02448-z
Int J Colorectal Dis. 2026 Jan 03. 41(1): 16

Clinical utility of longitudinal ctDNA monitoring by multiplex MS-ddPCR for risk stratification and follow-up in rectal cancer.

Edina D Lauridsen, Luisa Matos Do Canto, Signe Timm, Birgitte M Havelund, Jan Lindebjerg, Lars Henrik Jensen, Rikke Fredslund Andersen, Torben Frøstrup Hansen.

   INTRODUCTION: Personalized treatment strategies in rectal cancer aim to balance escalation and de-escalation based on recurrence risk. Accurately identifying which patients will benefit from each approach is essential for optimizing outcomes and guiding follow-up. However, current clinical methods lack the precision needed to reliably predict response and long-term prognosis.
METHODS: In this feasibility study, we evaluated the prognostic utility of a novel methylation-specific droplet digital PCR (MS-ddPCR) multiplex assay in 56 patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant treatment (nT) and surgery. Circulating tumor DNA (ctDNA) was analyzed at four time points (baseline, during nT, preoperatively, 6 months post-surgery). Associations between ctDNA status and dynamics with tumor regression grade (TRG), disease recurrence, and overall survival (OS) were assessed using receiver operating characteristics (ROC) analyses and survival statistics.
RESULTS: ctDNA was detected in 59% of the patients at baseline. Preoperative ctDNA had limited discriminative value for pathologic response, AUC 0.60 (95% CI 0.45-0.76). In contrast, ctDNA positivity 6 months postoperatively was strongly associated with recurrence within 2 years following surgery, AUC 0.96 (95% CI, 0.91-1.00). CtDNA positivity 6 months post-surgery was associated with inferior 2-year DFS (38% vs 94%, p for log-rank < 0.001) and 3-year OS (63% vs 100%, p for log-rank < 0.001).
CONCLUSION: With this MS-ddPCR assay, preoperative ctDNA showed limited prognostic value, whereas ctDNA 6 months postoperatively was strongly associated with recurrence and overall survival. The absence of an immediate postoperative sample limited assessment of early molecular response-a time point critical for guiding treatment decisions and follow-up strategies-underscoring the need for earlier sampling in future studies to optimize ctDNA-guided management. Given the small cohort and exploratory design, these findings are hypothesis-generating and support further validation of the assay in larger, prospective trials.

Keywords:  Biomarkers; CtDNA; Methylations; Multiplex ddPCR; Rectal cancer

DOI:  https://doi.org/10.1007/s00384-025-05055-w