bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2025–06–15
four papers selected by
Lara Paracchini, Humanitas Research



  1. BMC Cancer. 2025 Jun 06. 25(1): 1011
      
    Keywords:  Acceptability; Bilateral salpingectomy; Cancer prevention; Ovarian cancer; Risk-reducing salpingectomy
    DOI:  https://doi.org/10.1186/s12885-025-14384-6
  2. J Exp Clin Cancer Res. 2025 Jun 12. 44(1): 174
       BACKGROUND: Epithelial ovarian cancer (EOC) is a leading cause of cancer mortality in women, often diagnosed at advanced stages. While first-line treatments improve survival, relapses remain common, with 5-year survival rates below 40%. Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive EOC detection and monitoring. It may help assess treatment response, notably microscopic residual disease. Our objective was to compare two ctDNA characterization strategies in EOC for assessing tumor burden during first-line treatment: a tumor-informed approach based on somatic mutations and a tumor-type informed approach utilizing DNA methylation patterns.
    METHODS: In the tumor-informed approach, whole exome sequencing (WES) was performed on EOC tumor DNA and matched PBMCs from 22 patients to identify tumor-specific mutations. Personalized panels were then designed to track these mutations in plasma cfDNA. In the tumor-type informed approach, differentially methylated loci (DMLs) were identified by comparing EOC samples, healthy ovarian tissues, and PBMCs. A unique custom methylation panel was designed, and a support vector machine classifier was trained to distinguish between methylation profiles in plasma cfDNA from healthy donors and from EOC patients. Plasma samples from 47 advanced-stage EOC patients receiving chemotherapy and 54 healthy subjects were analyzed.
    RESULTS: For the tumor-informed approach, WES identified an average of 72 somatic mutations per patient. For the tumor-type informed approach, 52,173 DMLs were identified as tumor-specific markers. In 47 plasma samples tested by both approaches, ctDNA levels were significantly correlated (R = 0.56, p = 4.3 × 10-5), with 70.2% concordance in detection. At baseline, ctDNA was detected in 21/22 patients with the tumor-informed approach, and in 11/12 non-training baseline samples with the tumor-type-informed classifier. At end-of-treatment, the latter detected ctDNA in 16/22 samples, outperforming the former. Detection using this more sensitive approach was significantly associated with relapse (log-rank p = 0.009; hazard ratio = 9.44; 95% CI 1.22-73.26) and poorer overall survival (log-rank p = 0.041).
    CONCLUSION: The tumor-type informed classifier demonstrated sensitivity and specificity for ctDNA detection, outperforming the tumor-informed approach in monitoring EOC progression. Requiring fewer sequencing data, it offers a practical, efficient solution for clinical management of EOC.
    DOI:  https://doi.org/10.1186/s13046-025-03433-4
  3. Int J Gynecol Cancer. 2025 May 10. pii: S1048-891X(25)01049-7. [Epub ahead of print] 101929
       OBJECTIVE: Early surgical menopause is associated with a higher risk of mild cognitive impairment among women in the general population; this association has not been studied among women with a BRCA1 or BRCA2 mutation. This study aimed to describe the impact of clinical and host factors including bilateral oophorectomy on the probability of amnestic mild cognitive impairment among BRCA mutation carriers.
    METHODS: This cross-sectional study extends from a longitudinal observational study of hereditary breast and ovarian cancer that has been ongoing since 1995. The Cogniciti Brain Health Assessment was administered from 2017 to 2020 among 752 women with a BRCA mutation in Canada and the United States. The probability of amnestic mild cognitive impairment was derived from the age at test completion and 2 memory task results from the Cogniciti Brain Health Assessment, and was categorized as high or low. Self-reported details on clinical and host factors were collected from biennial research questionnaires.
    RESULTS: There were 21 (2.8%) women with a high probability of amnestic mild cognitive impairment and 731 (97.2%) women with a low probability. Women with a high probability were on average older at the time of cognitive assessment (63.9 vs 57.4 years, p < .001) and less likely to undergo oophorectomy for cancer prevention (55.0% vs 86.3%, p < .001) compared with women with a low probability. Among those who underwent oophorectomy for cancer prevention, women with a high probability were older at the time of surgery compared with those with a low probability (55.0 vs 46.3 years, p = .04).
    CONCLUSIONS: The findings suggest no short-term impact of bilateral oophorectomy on the probability of amnestic mild cognitive impairment among BRCA mutation carriers. A higher probability was predominantly attributed to older age at cognitive assessment. It is prudent to continue to monitor this population for potential long-term adverse effects following preventive surgery or cancer treatment.
    Keywords:  BRCA1; BRCA2; Cognition; Oophorectomy; aMCI
    DOI:  https://doi.org/10.1016/j.ijgc.2025.101929
  4. JNCI Cancer Spectr. 2025 Jun 11. pii: pkaf061. [Epub ahead of print]
       BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition that increases risk for colorectal, endometrial, and other cancers. Though population-based genomic screening programs identify individuals with LS, clinical presentation in such genomically ascertained populations is unknown.
    METHODS: MyCode is a healthcare system-based biobank that returns clinically actionable genomic screening results to participants, including pathogenic/likely pathogenic (P/LP) variants in LS genes (MLH1, MSH2, MSH6, PMS2). Adult cases (participants with an LS result) and controls (participants without a cancer predisposition variant matched to cases) reported their personal and family cancer histories. Rates of meeting National Comprehensive Cancer Network (NCCN) genetic testing guidelines and rates of colorectal and endometrial cancers in cases, controls, and their family members were calculated and compared.
    RESULTS: A total of 175 cases (10 MLH1, 7 MSH2, 83 MSH6, and 75 PMS2) and 169 controls were included. Of case pedigrees, 62/175 (35.4%) met NCCN criteria for LS evaluation. Case pedigrees were more likely (p < .001) to meet criteria than control pedigrees (4/169, 8.35%). Case probands had significantly higher rates of colorectal and endometrial cancer than controls (7.7% v 2.4%, p = .03 colorectal; 11.5% v 0%, p < .001 endometrial), as did their relatives (3.1% v 0.9%, p < .001 colorectal; 2.2% v 0.5%, p < .001 endometrial).
    CONCLUSIONS: NCCN guidelines missed 65% of cases with P/LP LS variants despite families having higher colorectal and endometrial cancer rates compared to controls. Genomic screening can assist in identifying individuals at risk for LS-related cancers, providing an opportunity to tailor risk management for cancer prevention and early detection.
    DOI:  https://doi.org/10.1093/jncics/pkaf061