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Abstract Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.

Objective: Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer. Methods: Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer. Results: Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760–0.889), histone-DNA complex (0.740; 95 % CI, 0.660–0.809), and neutrophil elastase (0.689; 95 % CI, 0.607–0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659–0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer. Conclusion: High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Pathologic confirmation of lymph node metastasis is important for risk stratification and the administration of adjuvant treatments. Therefore, comprehensive, systematic lymphadenectomy has been routinely performed but has been associated with various morbidities. Meanwhile, the concept of sentinel lymph node (SLN) mapping and biopsy has emerged and is now accepted as an alternative to conventional systematic lymphadenectomy in early-stage endometrial cancer. For better management of endometrial cancer, we conducted a literature review to summarize the role and diagnostic accuracy of the SLN mapping strategy in endometrial cancer. Evidence from the monumental and recent literature and ongoing clinical trials will be introduced.

Abstract Background To evaluate the impact of intraoperative hypotension and hemodynamic instability on survival outcomes in patients with high-grade serous ovarian carcinoma (HGSOC). Methods We retrospectively identified patients with HGSOC, who underwent primary or interval debulking surgery between August 2013 and December 2019. We collected anesthesia-related variables, including the arterial blood pressure measurements (at 1-min intervals) during the surgery of patients. The cumulative duration of mean arterial blood pressure (MAP) readings under 65 mmHg and two performance measurements (median performance error [MDPE] and wobble) were calculated. We investigated associations between the factors indicating hemodynamic instability and prognosis. Results In total, 338 patients were included. Based on the cumulative duration of MAP under 65 mmHg, we divided patients into two groups: ≥30 min and

Abstract Lgr5 has been identified as a marker of the stem/progenitor cells in the murine ovary and oviduct by lineage tracing. However, little is known regarding LGR5 expression or its functional significance in human ovary tissues. Here, using RNA in situ hybridization and/or immunohistochemistry, we thoroughly investigated LGR5 expression in normal human ovaries, fallopian tubes and various ovarian tumors. We discovered that LGR5 expression is negligible in the human ovary surface epithelium, whereas ovarian stromal cells normally express low levels of LGR5. Remarkably, fallopian tube epithelium, inclusion cysts and serous cystadenomas with a Müllerian phenotype expressed high levels of LGR5, and LGR5 expression was restricted to PAX8+/FOXJ1− secretory cells of the tubal epithelium. Strong stromal LGR5 expression without epithelial LGR5 expression was consistently observed in the path from serous cystadenoma to serous borderline tumor to low grade serous carcinoma (LGSC). Unlike LGSC, high grade serous carcinoma (HGSC), clear cell carcinoma, endometrioid carcinomas displayed various epithelial-stromal LGR5 expression. Notably, high levels of LGR5 expression were observed in serous tubal intraepithelial carcinoma, which slightly declined in invasive HGSC. LGR5 expression was significantly associated with improved progression-free survival in HGSC patients. Moreover, in vitro assays demonstrated that LGR5 expression suppressed tumor proliferation and migratory capabilities. Taken together, these findings indicate a tumor-suppressive role for LGR5 in the progression of HGSC.

Abstract Background The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer. Methods From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed. Results Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P

Abstract Background Mitochondrial dynamics (e.g. fission/fusion) play an important role in controlling chemoresistance in representative gynecologic malignancies, ovarian and cervical cancer. Processing the long form of Optic atrophy (L-Opa)1 is a distinctive character of mitochondrial fragmentation, associated with chemosensitivity. Here, we examined the role of prohibitin (Phb)1 in increasing L-Opa1 processing via the regulating mitochondrial protease, Oma1 and its direct interaction with p-p53 (ser15) and pro-apoptotic Bcl-2 antagonist/killer (Bak) 1 in the signaling axis and if this phenomenon is associated with prognosis of patients. Methods We compared Cisplatin (CDDP)-induced response of mitochondrial dynamics, molecular interaction among p-p53 (ser15)-Phb1-Bak, and chemoresponsiveness in paired chemosensitive and chemoresistant gynecologic cancer cells (ovarian and cervical cancer cell lines) using western blot, immunoprecipitation, sea horse, and immunofluorescence. Translational strategy with proximity ligation assessment in phb1-p-p53 (ser15) in human ovarian tumor sections further confirmed in vitro finding, associated with clinical outcome. Results We report that: (1) Knock-down of Phb1 prevents Cisplatin (cis-diamine-dichloroplatinum; CDDP) -induced changes in mitochondrial fragmentation and Oma1 mediated cleavage, and Opa1 processing; (2) In response to CDDP, Phb1 facilitates the p-p53 (ser15)-Phb1-Bak interaction in mitochondria in chemosensitive gynecologic cancer cells but not in chemoresistant cells; (3) Akt overexpression results in suppressed p-p53(Ser15)-Phb1 interaction and dysregulated mitochondrial dynamics, and (4) Consistent with in vitro findings, proximity ligation assessment (PLA) in human ovarian tumor sections demonstrated that p-p53(ser15)-Phb1-Bak interaction in mitochondria is associated with better chemoresponsiveness and clinical outcome of patients. Determining the molecular mechanisms by which Phb1 facilitates mitochondrial fragmentation and interacts with p53 may advance the current understanding of chemoresistance and pathogenesis of gynecologic cancer. Conclusion Determining the key molecular mechanisms by which Phb1 facilitates the formation of p-p53 (ser15)-Bak-Phb1 and its involvement in the regulation of mitochondrial dynamics and apoptosis may ultimately contribute to the current understanding of molecular and cellular basis of chemoresistance in this gynecologic cancer.

Abstract Objectives To investigate the impact of computed tomography (CT)-based, artificial intelligence-driven waist skeletal muscle volume on survival outcomes in patients with endometrial cancer. Methods We retrospectively identified endometrial cancer patients who received primary surgical treatment between 2014 and 2018 and whose pre-treatment CT scans were available (n = 385). Using an artificial intelligence-based tool, the skeletal muscle area (cm2) at the third lumbar vertebra (L3) and the skeletal muscle volume (cm3) at the waist level were measured. These values were converted to the L3 skeletal muscle index (SMI) and volumetric SMI by normalisation with body height. The relationships between L3, volumetric SMIs, and survival outcomes were evaluated. Results Setting 39.0 cm2/m2 of L3 SMI as cut-off value for sarcopenia, sarcopenia (

Abstract Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P

ObjectiveTumor-promoting inflammation is among the hallmarks of cancer. Prekallikrein is among the acute-phase reactants in the inflammatory response; moreover, neutrophils release nuclear contents into the extracellular space to create neutrophil extracellular traps (NET). We aimed to investigate the diagnostic and prognostic utilities of circulating plasma NET markers and prekallikrein for high-grade serous ovarian cancer (HGSOC).MethodsCirculating levels of three NET markers (histone-DNA complex, cell-free DNA, and neutrophil elastase) and prekallikrein were measured in 75 patients with HGSOC and 23 healthy controls. We used an area under the receiver operating characteristic curve (AUC) analysis to investigate their diagnostic and prognostic utilities for HGSOC.ResultsCompared with healthy controls, patients with HGSOC showed significantly higher levels of the three NET markers and prekallikrein. Patients with advanced-stage HGSOC showed significantly higher levels of the cell-free DNA (87.4 vs. 79.5 ng/ml; P = 0.013), compared with those with early-stage HGSOC. Further, the levels of histone-DNA complex, neutrophil elastase, and prekallikrein did not significantly differ according to the cancer stage. All markers showed significant diagnostic utility. Notably, a logistic regression-based model that comprised all four markers showed the strongest diagnostic power (AUC, 0.966; 95% confidence interval [CI], 0.933−1.000). Specifically, neutrophil elastase was identified as an independent poor prognostic factor for overall survival (adjusted hazard ratio [aHR], 10.17; 95% CI, 1.09−94.97; P = 0.042) and progression-free survival (aHR, 14.47; 95% CI, 1.52−137.35; P = 0.020) in patients with HGSOC.ConclusionsThe levels of the three NET markers and prekallikrein might be novel diagnostic and prognostic markers for HGSOC.

BackgroundA positive relationship was reported between metabolic syndrome and the risk of endometrial cancer. Studies on the relationship between metabolic syndrome and endometrial cancer have been mainly conducted in post-menopausal women. We aimed to investigate the risk of endometrial cancer according to metabolic syndrome and menopausal status using the Korean nationwide population-based cohort.MethodsWe enrolled 2,824,107 adults (endometrial cancer group; N = 5,604 and control group; N= 2,818,503) from the Korean National Health Insurance Service checkup database from January 1 to December 31, 2009. The median follow-up duration was 8.37 years. Metabolic syndrome was diagnosed as having at least three of the following five components: abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, raised blood pressure, and hyperglycemia. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate endometrial cancer risk.ResultsThe endometrial cancer risk was higher in the metabolic syndrome group than that in the non-metabolic syndrome group (HR, 1.362; 95% CI, 1.281–1.449). The association between metabolic syndrome and endometrial cancer risk was significant in the premenopausal subgroup (HR, 1.543; 95% CI, 1.39–1.713) and postmenopausal subgroup (HR, 1.306; 95% CI, 1.213–1.407). The incidence of endometrial cancer was more closely related to metabolic syndrome components in the pre-menopausal subgroup than those in the post-menopausal subgroup (for waist circumference, blood pressure, triglycerides and high-density lipoprotein cholesterol, all p for interaction

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Background/Aim: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinumresistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. Patients and Methods: We retrospectively divided patients with PRROC into two groups: bevacizumab plus chemotherapy (BEVCT group) and chemotherapy alone (CT group). Progressionfree survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. Results: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. Conclusion: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity. [ABSTRACT FROM AUTHOR]

Abstract Background To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy. Methods In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups. Results The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84–1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72–2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery. Conclusions More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy.

Sarcopenia, loss of skeletal muscle and function, is a common condition among the elderly and is known to cause adverse health outcomes and increased risk of morbidity and mortality. This progressive and generalized disorder imposes a considerable socioeconomic burden. Sarcopenia is observed commonly in cancer patients. As Asia is one of the fastest aging regions in the world, it is clear that incidences of both sarcopenia and ovarian cancer will increase together in Asian countries. Ovarian cancer patients are vulnerable to develop sarcopenia during the treatment course and progress of disease, and a considerable number of patients with ovarian cancer seems to have physical inactivity and sarcopenia already at the time of diagnosis. Therefore, management of sarcopenia should be conducted together in parallel with ovarian cancer treatment and surveillance. Thus, in this article, we will review the clinical importance of sarcopenia in the aspect of ovarian cancer. Definition of sarcopenia, diagnosis, etiology, and intervention will be also introduced.

ObjectiveTo compare the incidence and survival rates of primary ovarian clear cell carcinoma (OCCC) and ovarian serous carcinoma (OSC) from a nationwide collected database.MethodsWe extracted information of patients with primary OCCC and OSC from the Korea Central Cancer Registry recorded between 1999 and 2018, including age at diagnosis and the Surveillance, Epidemiology, and End Results summary stage. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Baseline characteristics and overall survival (OS) were compared between the OCCC and OSC groups.ResultsOverall, the incidence rate of primary OCCC increased markedly from 1999 (ASR, 0.16/100,000) to 2018 (0.76/100,000) (APC, 7.85%; P

The purpose of this study was to investigate the impact of sarcopenia and body composition change during primary treatment on survival outcomes in patients with early cervical cancer. We retrospectively identified patients diagnosed with 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 cervical cancer who underwent primary radical hysterectomy between 2007 and 2019. From pre-treatment CT scans (n = 306), the skeletal muscle area at the third lumbar vertebra (L3) and the waist skeletal muscle volume were measured using an artificial intelligence-based tool. These values were converted to the L3 and volumetric skeletal muscle indices by normalization. We defined L3 and volumetric sarcopenia using 39.0 cm2/m2 and the first quartile (Q1) value, respectively. From pre- and post-treatment CT scan images (n = 192), changes (%) in waist skeletal muscle and fat volumes were assessed. With the use of Cox regression models, factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Between the L3 sarcopenia and non-sarcopenia groups, no differences in PFS and OS were observed. In contrast, volumetric sarcopenia was identified as a poor prognostic factor for PFS (adjusted hazard ratio [aHR], 1.874; 95% confidence interval [CI], 1.028–3.416; p = 0.040) and OS (aHR, 3.001; 95% CI, 1.016–8.869; p = 0.047). During primary treatment, significant decreases in waist skeletal muscle (median, −3.9%; p < 0.001) and total fat (median, −5.3%; p < 0.001) were observed. Of the two components, multivariate analysis revealed that the waist fat gain was associated with worse PFS (aHR, 2.007; 95% CI, 1.009–3.993; p = 0.047). The coexistence of baseline volumetric sarcopenia and waist fat gain further deteriorated PFS (aHR, 2.853; 95% CI, 1.257–6.474; p = 0.012). In conclusion, baseline volumetric sarcopenia might be associated with poor survival outcomes in patients with early cervical cancer undergoing primary RH. Furthermore, sarcopenia patients who gained waist fat during primary treatment were at a high risk of disease recurrence.

Background: : Studies examining the relationship between obesity and female-specific cancers have been mainly conducted in Western populations. We aimed to investigate the risk of female-specific cancers according to obesity and menopausal status using a nationwide cohort in Korea. Methods: : We identified 2,708,938 women from the National Health Insurance Service cohort, and obtained baseline body mass index (BMI), waist circumference (WC), and other healthcare data, measured and collected during a health examinations and cancer-screening survey. By setting a normal weight/WC group (BMI, 18•5–22•9 kg/m2 or WC, 80•0–84•9 cm) as the reference, we conducted multivariate analyses using the Cox proportional hazard model to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for each cancer. Findings: : The total follow-up duration was 22389854•63 person-years. In post-menopausal women, the risk of breast, endometrial, and ovarian cancers significantly increased as the BMI classification level increased from normal to class II obesity (aHRs [95% CIs], 1•49 [1•38–1.61], 2•11 [1•81–2•46], and 1•38 [1•20–1•58], respectively). The risk of breast and endometrial cancers also increased as the WC classification increased from < 75•0 to ≥ 95•0 cm. With a WC of 80•0–84•9 cm as the reference, the lowest risk of breast and endometrial cancers was observed in WC < 75•0 cm (aHRs [95% CIs], 0•85 [0•81–0•89] and 0•75 [0•67–0•84], respectively) while the highest risk was observed in WC ≥ 95•0 cm (aHRs [95% CIs], 1•19 [1•10–1•29] and 1•56 [1•33–1•82], respectively). In pre-menopausal women, the risk of breast cancer significantly decreased in those with class I and II obesity compared to those with normal BMI (aHRs [95% CIs], 0•96 [0•92–0•999] and 0•89 [0•81–0•97], respectively), whereas the trends of endometrial and ovarian cancer incidence in pre-menopausal women were similar to those observed in post-menopausal women. For cervical cancer, only class II obesity was significantly associated with increased risks in both post-menopausal and pre-menopausal women (aHRs [95% CIs], 1•18 [1•01–1•39] and 1•27 [1•02–1•57], respectively). Interpretation: : In this large population-based cohort study in Korean women, we observed that the impact of obesity on the development of female-specific cancers differs according to the malignancy type and menopausal status. Similar trends were observed between Korean and Western women. Funding: : The Korea Health Industry Development Institute (no. HI16C2037).

BackgroundThe incidence of breast cancer has been gradually increasing in Korea. Recently, the elevated level of serum gamma-glutamyltransferase (GGT) has emerged to be associated with the development and progression of some malignancies. This study aimed to determine the effect of serum GGT levels on the risk of developing breast cancer in Korean women.MethodsWe used National Health Insurance Service Health Checkup data to examine the association between serum GGT levels and breast cancer development in Korean women. Women aged 40 years or older who participated in the Korean National Health Screening Examination between January 2009 and December 2009 and who did not develop any cancer within 1-year post examination were included in this analysis (n = 3,109,506). Cox proportional hazard regression analysis was conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOverall, an elevated serum GGT level was associated with the increased risk of developing breast cancer; compared to the Q1 group, the Q4 group showed a significantly increased breast cancer risk (HR: 1.120,95% CI: 1.08–1.162). Such a relationship was stronger in post-menopausal women than pre-menopausal women (HR: 1.173, 95% CI: 1.107–1.243; HR: 1.070, 95% CI:1.019–1.124). Women with a high GGT level (Q4) were also at an increased risk of developing carcinoma in situ (CIS) (HR: 1.114, 95% CI: 1.04–1.192). In post-menopausal women, the Q4 group also exhibited higher CIS risk (HR: 1.266, 95% CI: 1.132–1.416). However, no significant difference in the risk of developing CIS was observed between the Q1 and Q4 groups in pre-menopausal women. Further analysis revealed that obese, post-menopausal women with a high GGT level (Q4) were associated with an increased risk of developing breast cancer (HR: 1.214, 95% CI: 1.125–1.31) and CIS (HR: 1.348, 95% CI: 1.159–1.569).ConclusionsOur study results demonstrate that increased serum GGT level is a risk factor for developing breast cancer. The post-menopausal women group with obesity and elevated serum GGT level showed the highest incidence of breast cancer. Thus, serum GGT concentration could be a novel and potential risk factor for breast cancer. Further validation in different ethnic groups would be warranted.

The 8th Biennial Meeting of the Asian Society of Gynecologic Oncology took place in Taipei, Taiwan in December 2023. The meeting aimed to advance the study, prevention, and treatment of gynecological cancer in Asia through scientific exchange, collaboration, and education. The event featured presentations on cutting-edge research and high-technology practices related to gynecological cancer. Notably, studies presented at the meeting showed that durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab improved survival rates in patients with recurrent or metastatic cervical cancer, and carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib had a significant benefit in patients with advanced or recurrent endometrial cancer. The meeting also included symposia on various topics related to gynecologic oncology and featured social events such as a gala dinner and a laparoscopic surgery workshop. [Extracted from the article]

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate impact of germline BRCA mutational status on prognosis in patients with advanced ovarian cancer. Methods A total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study. We compared patients’ clinicopathological characteristics and survival outcomes after primary treatment according to germline BRCA mutational status. Treatment-related factors that might affect patients’ survival outcome were also investigated. Results Germline BRCA1/2 mutations were observed in 51 women (39.8%). There were no differences in age and serum CA-125 levels at the time of HGSOC diagnosis, use of neoadjuvant chemotherapy (NAC), extent of debulking surgery, and overall survival (OS) between the BRCA mutation and wild-type BRCA groups. In contrast, the BRCA mutation group displayed longer progression-free survival (PFS) (median, 22.9 vs. 16.9 months, P = 0.001). Multivariate analyses identified germline BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted HR, 0.502; 95% CI, 0.318–0.795; P = 0.003). In the wild-type BRCA group, patients who received NAC as the primary treatment had shorter PFS compared to those who received primary debulking surgery (PDS) (median, 14.2 vs. 16.9 months, P = 0.003). However, in the BRCA mutation group, PFS did not differ between the NAC and PDS groups (P = 0.082). Conclusions In advanced-stage HGSOC, patients with germline BRCA1/2 mutations have better prognosis with longer PFS than those lacking BRCA mutations. Prognosis after NAC was different according to the BRCA mutational status.

Abstract Background Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC. Methods In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified. Results Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P

Ovarian cancer is one of the leading causes of cancer-related deaths in gynecological malignancies. Over 70% of ovarian cancer cases are high-grade serous ovarian cancers and have high death rates due to their resistance to chemotherapy. Despite advances in surgical and pharmaceutical therapies, overall survival rates are not good, and making an accurate prediction of the prognosis is not easy because of the highly heterogeneous nature of ovarian cancer. To improve the patient’s prognosis through proper treatment, we present a prognostic prediction model by integrating high-dimensional RNA sequencing data with their clinical data through the following steps: gene filtration, pre-screening, gene marker selection, integrated study of selected gene markers and prediction model building. These steps of the prognostic prediction model can be applied to other types of cancer besides ovarian cancer.