Search Results (206)

Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world rates and determinants of germline and somatic BRCA1/2 testing and subsequent PARPi utilisation in Australia using a national clinical quality registry. Methods: This multi-centre cohort study analysed data from 1503 women with non-mucinous EOC diagnosed between May 2017 and July 2022, captured by the Australian National Gynae-Oncology Registry (NGOR). We evaluated rates of germline and somatic testing and PARPi use, using multivariate logistic regression to identify associated clinical and demographic factors. Results: Overall germline and somatic testing rates were 68% and 32%, respectively. For the high-grade serous ovarian cancer (HGSOC) cohort, rates were higher, at 78% and 39%, respectively. Germline testing was significantly less likely for women aged >80 years (OR 0.49), those in regional areas (OR 0.61), and those receiving single-modality treatment. Somatic testing uptake increased significantly following public reimbursement for PARPi (p = 0.004). Among eligible women with a newly diagnosed BRCA pathogenic variant and advanced disease (n = 110), 52% commenced first-line maintenance PARPi. Conclusions: This national study offers valuable insights into Australian ovarian cancer care, highlighting opportunities to enhance testing equity for older women (aged >80) and regional patients. Furthermore, it identifies the translation of a positive test into PARPi therapy as a complex area that warrants further collaborative investigation to optimise patient outcomes. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571 Full article

Objectives: The current study underscores the potential role of miRNAs, specifically miR-3173 and miR-155, as promising biomarkers for breast and ovarian cancers (BC and OC). The primary objective was to evaluate the expression levels of these miRNAs in cancer patients compared to healthy individuals, assess their diagnostic accuracy, and explore their associations with cancer progression and prognosis. Methods: This study involved 60 participants, comprising 30 patients diagnosed with primary BC and 30 patients with epithelial ovarian cancer (EOC). Tumor tissue samples were obtained from all patients for molecular analysis. For control comparisons, adjacent non-tumorous tissues from both groups were utilized. miR-3173 and miR-155 expression levels were measured using real-time PCR (qPCR). The diagnostic accuracy of both miRNAs was evaluated through receiver operating characteristic (ROC) curve analysis, calculating sensitivity and specificity for distinguishing cancer cases from healthy controls. Additionally, the association of miR-155 with metastasis was explored, and miR-3173’s correlation with poor progression-free survival in BC patients was assessed using Kaplan–Meier survival curve analysis. Results: Both miRNAs were found to be significantly upregulated in cancer patients compared to healthy individuals, with miR-155 exhibiting high sensitivity and specificity for distinguishing BC and OC cases. Notably, miR-155 is associated with metastasis, which aligns with previous research, suggesting its role as an oncogene in epithelial OC. Meanwhile, the elevated expression of miR-3173 correlates with poor progression-free survival in BC patients, marking it as a potential prognostic marker. However, these results highlight the complexity of miRNA expression in cancer progression, as miR-3173 showed varied associations with different types of cancer. Despite these challenges, the ROC curve analysis for both miRNAs is promising with high sensitivity and specificity for both BC and OC. Conclusion: The study findings are particularly significant in the context of early diagnosis and monitoring cancer progression, yet further investigations involving larger cohorts and diverse populations are needed to validate these results. Future studies should focus on expanding sample sizes, refining the understanding of miRNA roles in tumor progression, and exploring their potential as therapeutic targets. These advancements could significantly enhance personalized treatment strategies for breast and ovarian cancer, improving patient outcomes. Full article

Ovarian cancer is the most lethal gynecologic malignancy, which causes 313,959 new cases and 207,252 deaths worldwide annually. The lack of specific symptoms, together with no effective screening tools, results in 75% of patients receiving their diagnosis at an advanced stage. The combination of cytoreductive surgery with platinum-based chemotherapy plays a pivotal role in the treatment of advanced epithelial ovarian cancer, but patients still experience poor long-term survival because of frequent relapses and chemotherapy resistance. The treatment landscape has evolved because bevacizumab and Poly-ADP Ribose Polymerase inhibitors now serve as frontline and maintenance therapies for homologous recombination-deficient tumors. Treatment decisions for recurrent disease depend on platinum sensitivity assessment, which determines the appropriate therapeutic approach, while targeted agents deliver significant benefits to specific patient groups. The development of antibody-drug conjugates such as mirvetuximab soravtansine and immunotherapy, including checkpoint inhibitors and cancer vaccines, demonstrates promising investigative potential. The precision of therapy improves through the use of emerging biomarkers and molecular profiling techniques. The future management of this disease may change because of innovative approaches that include adoptive cell therapy, cytokine therapy, and oncolytic viruses. The progress made in ovarian cancer treatment still faces challenges when it comes to drug resistance, survival improvement, and life quality preservation. The development of translational research alongside clinical trials remains essential to bridge treatment gaps while creating personalized therapies based on molecular and clinical tumor characteristics. Full article

Background/Objectives: Bowel resection may be necessary during cytoreductive surgery (CS) in advanced epithelial ovarian cancer to achieve complete tumor removal. However, concerns about increased perioperative risks and unclear survival benefits have led to ongoing debate. This study aimed to evaluate the impact of bowel resection on perioperative mortality and overall survival (OS) in patients undergoing CS. Methods: We retrospectively reviewed 127 patients with FIGO stage IIB–IV epithelial ovarian cancer who underwent primary or interval CS between 2007 and 2021. Patients were stratified based on the performance of bowel resection. Clinical, surgical, and survival data were analyzed using Kaplan–Meier survival analysis and Cox proportional hazards modeling. Primary outcomes were 90-day mortality and OS. Results: Bowel resection was performed in 58 patients (46%) with more extensive disease and poorer ECOG performance scores. Although the resection group had increased perioperative risks (e.g., higher transfusion rates and ICU use), OS was similar between groups (log-rank p = 0.122). Multivariate analysis identified that increasing age (HR = 1.042, p = 0.005) was independently associated with poorer OS, whereas lymph node dissection (HR = 0.450, p = 0.003) and undergoing primary CS (HR = 0.540, p = 0.047) were associated with improved survival. Bowel resection was not independently associated with OS. Conclusions: Bowel resection does not adversely affect OS when optimal cytoreduction is achieved. Although it increases perioperative complexity, it can be safely incorporated into CS in selected patients. These findings support its use as part of an individualized surgical strategy for advanced ovarian cancer. Full article

Background: Advanced-stage epithelial ovarian cancer is associated with variable survival outcomes, despite standardized treatments. Identifying reliable and accessible prognostic markers is critical to guide clinical decision-making. Objective: The aim of this study was to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with FIGO stage III–IV epithelial ovarian cancer. Methods: In this retrospective cohort study, 89 patients diagnosed between 2018 and 2023 were analyzed. The mGPS was calculated from pre-treatment serum C-reactive protein (CRP) and albumin levels. Overall survival (OS) was assessed using Kaplan–Meier and Cox regression analyses. Results: The median OS was 32.3 months. When stratified by mGPS categories, the 2-year survival rates were 94%, 75%, and 34% in the mGPS 0, 1, and 2 groups, respectively (p < 0.001). In the multivariate Cox proportional hazards model, both mGPS (HR = 1.85; 95% CI: 1.12–3.07; p = 0.016) and ECOG performance status (HR = 1.67; 95% CI: 1.02–2.75; p = 0.043) were identified as independent predictors of overall survival. Conclusions: The mGPS is a simple, low-cost, and independently predictive tool for overall survival in advanced ovarian cancer. By capturing both systemic inflammation and nutritional status, it enhances risk stratification and may support individualized treatment planning. Prospective validation is warranted. Full article

Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with or without ascites), endometriosis, uterine fibroids, adenomyosis, pelvic inflammatory disease, and pregnancy. This review aims to explore the role of CA125 in non-malignant serous effusions, highlighting its diagnostic and prognostic potential beyond the realm of oncology. Methods: A comprehensive literature search was conducted across multiple databases and clinical trial registries. Eligible studies included full-text original research articles, reviews, and case reports published in English over the past 10 years. Inclusion criteria were limited to studies involving human subjects and focused on the role of CA125 in non-malignant serous effusions. Results: CA125 is produced by coelomic epithelial cells lining the ovary, pleura, pericardium, and peritoneum. Its serum concentration is not significantly influenced by age, body weight, or renal function, even in the advanced stages of the disease. In peritoneal conditions, CA125 is synthesized by mesothelial cells and serves as a potential marker of peritoneal involvement. The prevailing pathophysiological mechanism suggests that mechanical stretching of mesothelial cells due to ascitic pressure stimulates CA125 release. Similarly, in heart failure, mesothelial cells of the pericardium produce CA125, which correlates with congestion severity, supports risk stratification, and may inform diuretic therapy. Conclusions: While a threshold of 35 U/mL is established for malignancy, no standardized cutoff exists for CA125 in non-malignant conditions. The utility of CA125 measurement in peritoneal, pleural, or pericardial effusions—and cardiovascular diseases such as acute heart failure—for purposes of differential diagnosis, treatment guidance, or prognostication warrants further investigation through prospective clinical trials. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) is a complex disease characterized by heterogeneous clinical, pathological, and molecular features. Diagnosed frequently at advanced stages, it presents significant challenges in treatment due to the risks of resistance and recurrence. While bevacizumab, by inhibiting angiogenesis, offers a valuable therapeutic option for platinum-sensitive recurrent ovarian cancer (PSROC), its impact on overall survival (OS) remains incompletely understood. This retrospective study aims to compare treatment responses in high- and low-risk groups of patients with PSROC and to evaluate the effects of bevacizumab on survival within these risk strata. Materials and Methods: This retrospective study included patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV EOC who received chemotherapy or chemotherapy plus bevacizumab for platinum-sensitive recurrence. Patients were classified according to risk groups, and their clinicopathological characteristics were compared. Survival analyses and adverse events regarding risk groups and bevacizumab use were examined. In this study, the effect of bevacizumab on survival in patients with PSROC was evaluated for the first time according to risk stratification, and the relationship between treatment response and survival was investigated according to recurrence localization. Results: Of the 174 patients included in this study, 102 (58.6%) were classified as low risk and 72 (41.4%) were classified as high risk. Significant differences in survival were observed between the risk groups. In the low-risk group, progression-free survival and overall survival were markedly longer compared to the high-risk group. Median PFS was 13.7 months in the low-risk group and 10.8 months in the high-risk group (p = 0.007). Median OS was 36.5 and 23.5 months, respectively (p = 0.003). In low-risk patients, the addition of bevacizumab to chemotherapy significantly increased median PFS (13.5 months vs. 9.7 months, p = 0.029); however, this advantage did not translate into a significant overall survival benefit (39.4 months vs. 33.3 months, p = 0.669). Conversely, in the high-risk group, bevacizumab use provided significant benefits in both PFS and OS. Median PFS was 13.9 months in the bevacizumab group and 8.8 months in the control group (p < 0.001). Median OS was calculated as 36.5 and 23.2 months, respectively (p < 0.001). Conclusions: Our study is among the first to comprehensively compare the effectiveness of bevacizumab treatment in patients with platinum-sensitive recurrent ovarian cancer based on clinical risk groups and recurrence patterns using real-world data. The current literature lacks a comprehensive analysis that simultaneously evaluates these two critical parameters. In this respect, our study aims to contribute to developing more personalized treatment strategies for specific patient subgroups. Full article

Epithelial ovarian cancer (EOC) is diagnosed at an advanced stage in over half of the patients and its prognosis remains unfavorable. CA125, one of the most frequent positive tumor markers in patients with EOC, has certain limitations. Therefore, more accurate clinical biomarkers are needed. Liquid biopsy with cancer related molecules, such as circulating tumor DNA, is a new option for cancer diagnosis and prognosis. We explored the potential of plasma metabolomic and proteomic analyses as novel monitoring methods for the patients with EOC. Of seven patients, six experienced disease recurrence or progression. CA125 plasma measurements were conducted for disease monitoring. Plasma metabolome and proteome analyses were performed using liquid chromatography–tandem mass spectrometry. Ten and four metabolome indicators were significantly increased and decreased in association with chemotherapeutic resistance, respectively. In addition, thirty-seven and nine proteins displayed high and low levels associated with chemotherapeutic resistance, respectively. Several metabolome pathways and protein concentrations corresponded to the clinical course of each patient. This pilot study suggested the potential of the assessment of metabolome and proteome analysis as a useful tool for developing novel monitoring biomarkers for patients with recurrent EOC. Full article

Mucin, a heavily glycosylated glycoprotein, serves an important function in forming protective and immune defense barriers against the exterior environment on epithelial surfaces. While secreted-type mucins are involved in mucous production, transmembrane mucins, which contain O-glycosylated tandem repeats, play a pivotal role in cellular signaling, especially in immune modulation and mediating inflammatory response. However, dysregulation in mucin expressions, such as MUC1, MUC2, MUC4, MUC5AC, and MUC16, have been observed in many cancer cells. More specifically, alterations in the expression and glycosylation of MUC1 have been associated with the upregulation of pathways involving the cell proliferation, angiogenesis, migration, and invasion of cancer cells. With mucin’s extensive involvement in cancer biology, several mucin biomarkers, such as CA125, CA19-9, and CEA, have been utilized as diagnostic and prognostic monitoring biomarkers in ovarian, pancreatic, and colon cancer. Vaccines and antibody therapy against abnormal mucin glycosylation have also been investigated for potential therapy for mucin-related cancers that are resistant to traditional chemotherapy agents. Despite the lack of specificity in mucin biomarkers and challenges in efficient drug delivery systems, the current advancement in mucin-targeted immunotherapy highlighted the pivotal potential in developing therapeutic targets to improve cancer prognosis. Full article

Folate receptor alpha (FRα), a glycosylphosphatidylinositol-anchored glycoprotein encoded by the FOLR1 gene, plays a crucial role in folate transport during cell growth and development. While minimally expressed in most normal adult tissues, FRα is frequently overexpressed in several epithelial malignancies, particularly in high-grade serous ovarian carcinoma. An immunohistochemical (IHC) evaluation of FRα expression using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay is now approved as a companion diagnostic for selecting patients eligible for mirvetuximab soravtansine, an FRα-targeted antibody–drug conjugate. Clinical trials such as SORAYA and MIRASOL have demonstrated significant clinical benefit in platinum-resistant epithelial ovarian cancer patients with high FRα expression (≥75% of tumor cells with moderate to strong membrane staining). This review summarizes the biological significance of FRα in ovarian cancer progression, its predictive value for targeted therapy, and the technical aspects of IHC assessment, including scoring interpretation and pre-analytical variables. We also discuss heterogeneity in FRα expression across histological subtypes and tumor sites, as well as the impact of archival versus fresh tissue. Understanding FRα expression patterns across histologic subtypes and tissue samples is critical for optimizing clinical decision-making and expanding the role of FRα-targeted therapies in gynecologic oncology. Full article

Homologous recombination deficiency (HRD) is a key biomarker associated with increased sensitivity to PARP inhibitors (PARPi) in advanced epithelial ovarian cancer. Accurate identification of HRD status is essential for selecting patients most likely to benefit from these therapies. Current diagnostic approaches combine sequencing to detect mutations in homologous recombination repair genes—particularly BRCA1 and BRCA2—with genome-wide analysis of structural genomic alterations indicative of HRD. This review briefly outlines the biological basis of HRD and its clinical significance and then focuses on currently available assays for HRD assessment. We compare their molecular strategies, including the use of targeted gene panels and genomic instability metrics such as loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. The review also highlights the strengths and limitations of each platform and discusses their role in guiding clinical decision-making. Challenges related to dynamic tumor evolution and the interpretation of HRD status in recurrent disease settings are also addressed. Full article

Extracellular vesicles (EVs) play pivotal roles in tumor progression and metastasis by mediating intercellular communication within the tumor microenvironment. In this study, we identified two novel EX cargo proteins—UBE2NL and HIST2H3PS2—derived from highly aggressive epithelial ovarian cancer (EOC) cells and mesenchymal-type ovarian stromal progenitor cells (MSC-OCSPCs) but absent in less aggressive SKOV3 cells. Quantitative proteomic profiling via LC-MS/MS and TCGA-integrated analysis revealed that high expression of these genes correlated with advanced tumor stages and poor overall survival in EOC, and high HIST2H3PS2 expression predicted poor survival in endometrial cancer (EC). Functionally, UBE2NL and HIST2H3PS2 overexpression promoted EOC cell invasiveness, which was further enhanced by EX-mediated autocrine and paracrine effects. In contrast, the knockdown of UBE2NL reduced cell invasiveness and prolonged mouse survival in vivo. Moreover, HIST2H3PS2-enriched EXs significantly increased peritoneal dissemination and ascites in murine models. These findings suggest that EX-packaged UBE2NL and HIST2H3PS2 drive tumor aggressiveness and metastasis in gynecologic cancers, highlighting their potential as prognostic biomarkers and therapeutic targets. Full article

Ovarian cancer is one of the most deadly gynecological cancers, with over 300 thousand new cases per year, most of which are diagnosed in advanced stages. The limited availability of effective biomarkers and lack of characteristic symptoms make early diagnosis difficult, resulting in a five-year survival rate of 30–40%. Mutations in the BRCA1 and BRCA2 genes and abnormalities of signaling pathways such as PI3K/AKT and TP53 play a key role in the progression of ovarian cancer. The immune system, which can act against tumors, often supports tumor development in the ovarian cancer microenvironment through immunoevasion, which is influenced by cytokines such as IL-6, IL-10, and TGF-β. Epithelial-to-mesenchymal transition (EMT) allows cancer cells to acquire mesenchymal characteristics, increasing their invasiveness and metastatic capacity. Immunological factors, including pro-inflammatory cytokines and signals from the tumor microenvironment regulate the EMT process. This review aims to present the role of EMT in ovarian cancer progression, its interactions with the immune system, and potential biomarkers and therapeutic targets. Modulation of the immune response and inhibition of EMT may constitute the basis for personalized therapies, which opens new possibilities for improving the prognosis and efficacy of treatment in patients with ovarian cancer. Full article