Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Trends of Ovarian Cancer Incidence by Histotype and Race/Ethnicity in the United States 1992-2019.

The effect of risk factors on ovarian cancer differs by histotype, and the prevalence of such risk factors varies by race/ethnicity. It is not clear how ovarian cancer incidence has changed over time by histotype and race/ethnicity. We used the Surveillance, Epidemiology, and End Results Program (SEER-12) 1992-2019 data to examine the trend of ovarian cancer incidence for three histotypes (high-grade serous N = 19,691, endometrioid N = 3,212, and clear cell N = 3,275) and four racial/ethnic groups (Asian/Pacific Islander, Hispanic, non-Hispanic Black, and non-Hispanic White). Joinpoint and age-period-cohort analyses were conducted to analyze ovarian cancer incidence trends. High-grade serous cancer was the most common histotype, but its incidence has significantly decreased over time for all racial/ethnic groups; the decrease was largest for non-Hispanic White women (average annual percent change AAPC during 2010-2019 = -6.1; 95% confidence interval (CI), -8.0 to -4.2). Conversely, clear cell cancer was most common in the Asian/Pacific Islanders, and its incidence has increased over time, particularly among Hispanic and Asian/Pacific Islander women (AAPC during 2010-2019 = 2.8; 95% CI, 0.8 to 4.7, and AAPC = 1.5; 95% CI, 0.7 to 2.2, respectively). Endometrioid cancer incidence has decreased in non-Hispanic White but increased in Hispanic women (AAPC during 2010-2019 = -1.3; 95% CI, -1.9 to -0.8, and AAPC = 3.6; 95% CI, 1.0 to 6.3, respectively). The differential incidence trends by histotype and race/ethnicity underscore the need to monitor incidence and risk factor trends across different groups and develop targeted preventive interventions to reduce the burden of ovarian cancer and disparity by race/ethnicity. Significance: During 1992-2019, high-grade serous ovarian cancer incidence has decreased while clear cell cancer incidence has increased regardless of race/ethnicity. Endometrioid cancer incidence has decreased in non-Hispanic White but increased in Hispanic women. Differential ovarian cancer incidence trends highlight the need for targeted preventive interventions by histotype and race/ethnicity.

Assessing frequency and clinical outcomes of BRCA mutated ovarian cancer in Saudi women.

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.

Racial disparities in non-recommendation of adjuvant chemotherapy in stage II-III ovarian cancer.

OBJECTIVES: To identify patient factors associated with not receiving a recommendation for adjuvant chemotherapy after primary surgery for ovarian cancer. METHODS: This retrospective cohort study used the National Cancer Database (NCDB) data from 2004 to 2015 to identify patients with stage II-III ovarian cancer who underwent primary surgery. Multivariate logistic regression analyses evaluated factors associated with notation in the NCDB that "chemotherapy was not recommended/administered because it was contraindicated due to patient risk factors (i.e., comorbid conditions, advanced age)." Survival data were assessed via Kaplan-Meier analyses. RESULTS: Of the 48,245 patients who met the inclusion criteria, 522 (1.08%) did not receive adjuvant chemotherapy because it was determined to be contraindicated. In multivariate analyses, independent predictors for not receiving a recommendation for adjuvant chemotherapy were age ≥ 70 years old (adjusted odds ratio, aOR = 2.43, p < 0.0001), non-zero Charlson-Deyo comorbidity scores (score 1, aOR = 1.41, p = 0.002; score ≥ 2, aOR = 2.57, p < 0.0001), and Black race (aOR = 2.12, p < 0.0001). For Black patients, recommendation against adjuvant chemotherapy occurred at a younger median age (64.5 years vs. 72 years) and was associated with lower 5-year survival (25.9% vs. 40.3%, p < 0.0001). CONCLUSIONS: Patients with ovarian cancer who underwent surgery but did not receive chemotherapy "because it was contraindicated due to patient risk factors" were older and had higher comorbidity scores. Even after controlling for these differences, Black patients were disproportionately not recommended for chemotherapy, which was associated with worse survival. Determining eligibility for adjuvant chemotherapy requires an individualized approach, and the possible influence of racial bias on risk estimation should be further investigated.

DNA Methylation Profiles of Ovarian Clear Cell Carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC. METHODS: We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways. RESULTS: Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 (N = 137), Cluster 1 cases (N = 134) presented at a more advanced stage, were less likely to be of Asian ancestry, and tended to have poorer outcomes including macroscopic residual disease following primary debulking surgery (P < 0.10). Subset analyses of targeted tumor sequencing and IHC data revealed that Cluster 1 tumors showed TP53 mutation and abnormal p53 expression, and Cluster 2 tumors showed aneuploidy and ARID1A/PIK3CA mutation (P < 0.05). Cluster-defining CpGs included 1,388 CpGs residing within 200 bp of the transcription start sites of 977 genes; 38% of these genes (N = 369 genes) were differentially expressed across cluster in transcriptomic subset analysis (P < 10-4). Differentially expressed genes were enriched for six immune-related pathways, including IFNα and IFNγ responses (P < 10-6). CONCLUSIONS: DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways. IMPACT: This work serves as a foundation for integrative analyses that better understand the complex biology of OCCC in an effort to improve potential for development of targeted therapeutics.

Nurse-led exercise and cognitive-behavioral care against nurse-led usual care between and after chemotherapy cycles in Han Chinese women of ovarian cancer with moderate to severe levels of cancer-related fatigue: A retrospective analysis of the effectiveness.

ABSTRACT: Women with ovarian cancer are reported to fatigue over time. Moderate to severe levels of cancer-related fatigue is fluent in Han Chinese patients with cancer. Comprehensive Cancer Network guidelines are recommending exercise and cognitive behavioral therapy to reduce cancer-related fatigue. Exercise is an easy, cost-effective, and non-pharmacological approach. The objective of the study was to evaluate the effectiveness of nurse-led exercise and cognitive-behavioral care against nurse-led usual care in Han Chinese women of ovarian cancer regarding cancer-related fatigue, depressive symptoms, and sleep quality.Han Chinese women with moderate to severe levels of cancer-related fatigue have received 30 minutes, 5 times/week nurse-led exercise and 60 min/week cognitive-behavioral care (EC cohort, n = 118) or nurse-led usual care regarding educations and recommendations only (UC cohort, n = 126) or have not received nurse-led exercise, cognitive-behavioral care, educations, and recommendations (NC cohort, n = 145) between and after chemotherapy cycles. The Piper Fatigue Scale, the Zung Self-rating Depression Scale, and Pittsburgh Sleep Quality Index questionnaires were evaluated at the start and the end of non-pharmacological treatment.At the end of treatment as compared to the start of treatment, only women of EC cohort had decrease Piper Fatigue Scale (5.40 ±â€Š1.49/woman vs 6.06 ±â€Š1.49/woman, P < .0001, q = 4.973) and Zung Self-rating Depression Scale score (48.67 ±â€Š4.24/woman vs 49.93 ±â€Š4.29/woman, P = .001, q = 3.449). Also, at the end of treatment, as compared to the start of treatment, only women of EC cohort have increased Pittsburgh Sleep Quality Index score (14.76 ±â€Š2.18/woman vs 13.94 ±â€Š2.90/woman, P = .045, q = 3.523). Only exercise and cognitive-behavioral care were successful in a decrease in the numbers of women with depression (the Mandarin Chinese version of the Zung Self-rating Depression Scale score >53, 32 vs 16, P = .015).Nurse-led exercise and cognitive-behavioral care can help Han Chinese women with ovarian cancer to decrease cancer-related fatigue and depression. Also, it can improve the quality of sleep.Evidence Level: 4.Technical Efficacy: Stage 5.

A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene.

BACKGROUND: Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function in homologous recombination (HR) of DNA, could involve pathogenic variants in other DNA repair pathway genes. METHODS: Whole exome sequencing was used to identify rare variants in HR genes in a BRCA1 and BRCA2 pathogenic variant negative OC family of French Canadian (FC) ancestry, a population exhibiting genetic drift. OC cases and cancer-free individuals from FC and non-FC populations were investigated for carrier frequency of FANCI c.1813C>T; p.L605F, the top-ranking candidate. Gene and protein expression were investigated in cancer cell lines and tissue microarrays, respectively. RESULTS: In FC subjects, c.1813C>T was more common in familial (7.1%, 3/42) than sporadic (1.6%, 7/439) OC cases (P = 0.048). Carriers were detected in 2.5% (74/2950) of cancer-free females though female/male carriers were more likely to have a first-degree relative with OC (121/5249, 2.3%; Spearman correlation = 0.037; P = 0.011), suggesting a role in risk. Many of the cancer-free females had host factors known to reduce risk to OC which could influence cancer risk in this population. There was an increased carrier frequency of FANCI c.1813C>T in BRCA1 and BRCA2 pathogenic variant negative OC families, when including the discovery family, compared to cancer-free females (3/23, 13%; OR = 5.8; 95%CI = 1.7-19; P = 0.005). In non-FC subjects, 10 candidate FANCI variants were identified in 4.1% (21/516) of Australian OC cases negative for pathogenic variants in BRCA1 and BRCA2, including 10 carriers of FANCI c.1813C>T. Candidate variants were significantly more common in familial OC than in sporadic OC (P = 0.04). Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the Fanconi anaemia (FA) pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level, destabilized by DNA damaging agent treatment in both HeLa and OC cell lines, and exhibited sensitivity to cisplatin but not to a poly (ADP-ribose) polymerase inhibitor. By tissue microarray analyses, FANCI protein was consistently expressed in fallopian tube epithelial cells and only expressed at low-to-moderate levels in 88% (83/94) of OC samples. CONCLUSIONS: This is the first study to describe candidate OC variants in FANCI, a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that pathogenic FANCI variants may modify OC risk in cancer families.

High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients.

OBJECTIVE: Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. MATERIALS AND METHODS: 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. RESULTS: Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). CONCLUSION: Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

Germline mutations in Black patients with ovarian, fallopian tube and primary peritoneal carcinomas.

OBJECTIVE: Routine genetic testing for ovarian cancer and identification of germline mutations can help improve early detection of cancer as well as guide treatment. Knowledge of genetic counseling and referral rates for genetic testing has been lower for Black patients, compared to White patients. We aimed to describe the demographics and presence of germline mutations in Black individuals with ovarian, fallopian tube or peritoneal carcinoma at two large academic institutions. METHODS: Fifty-one Black patients with invasive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma were identified via institutional tissue banks over a 20-year time-period. Germline DNA was sequenced using BROCA, a targeted capture and parallel sequencing assay that identified pathogenic germline mutations in ovarian carcinoma susceptibility genes. RESULTS: Germline mutations in ovarian cancer susceptibility genes were found in 25.5% of women, most commonly BRCA1 and BRCA2. This mutation frequency mirrors those previously described among predominantly White populations. Our data suggests there may be an advantage in survival among those with germline mutations, although this was not statistically significant. CONCLUSIONS: Given similar frequencies of germline mutations between Black and White patients with ovarian cancer, we conclude that there are not major differences in the genetic predisposition to ovarian carcinoma. Equitable access to genomic advancements including germline and tumor sequencing would facilitate equal access to PARP inhibitors, the standard of care for patients with BRCA mutated advanced ovarian cancer.

Disparities in ovarian cancer treatment and overall survival according to race: An update.

OBJECTIVE: To determine whether guideline non-adherence is associated with Black race. METHODS: A retrospective review of National Cancer Database records of women diagnosed with epithelial ovarian cancer from 2012 to 2016 who identified as "White" or "Black" was performed. Exposure was adherence or non-adherence to National Comprehensive Cancer Network guidelines for treatment. Outcomes were differences in disease characteristics and overall survival in months. RESULTS: Of the 29,948 eligible patients, 93% (n = 27,744) were White and 7% (n = 2204) were Black. Having stage IV disease (OR 1.45, 95% CI 1.23-1.70; P < 0.001) and treatment in a comprehensive (OR 1.58, 95% CI 1.16-2.15; P = 0.0039) or academic (OR 2.30, 95% CI 1.70-3.12; P < 0.001) treatment facility were associated with Black race. Adherence to guidelines did not predict Black race (OR for adherence 1.0021, 95% CI 0.89-1.13; P = 0.97). Median survival for White patients with adherent care was 63.4 months and 51.4 months for Black patients (P = 0.0001). Median survival for White patients with non-adherent care was 60.5 months and 47.2 months for Black patients (P < 0.0001). Median overall survival was 61.1 months in White patients and 49.3 months in Black patients (P < 0.0001). CONCLUSIONS: Our data suggest that while Black patients and patients who receive non-NCCN guideline directed care have worse survival outcomes, guideline adherence is not independently associated with Black race. We must consider other socioeconomic, environmental and system factors that are contributing to the survival discrepancy in Black patients with ovarian cancer.

A multi-ethnic analysis of immune-related gene expression signatures in patients with ovarian clear cell carcinoma.

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation, and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Genital Powder Use and Risk of Epithelial Ovarian Cancer in the Ovarian Cancer in Women of African Ancestry Consortium.

BACKGROUND: Genital powder use is more common among African-American women; however, studies of genital powder use and ovarian cancer risk have been conducted predominantly in White populations, and histotype-specific analyses among African-American populations are limited. METHODS: We used data from five studies in the Ovarian Cancer in Women of African Ancestry consortium. Participants included 620 African-American cases, 1,146 African-American controls, 2,800 White cases, and 6,735 White controls who answered questions on genital powder use prior to 2014. The association between genital powder use and ovarian cancer risk by race was estimated using logistic regression. RESULTS: The prevalence of ever genital powder use for cases was 35.8% among African-American women and 29.5% among White women. Ever use of genital powder was associated with higher odds of ovarian cancer among African-American women [OR = 1.22; 95% confidence interval (CI) = 0.97-1.53] and White women (OR = 1.36; 95% CI = 1.19-1.57). In African-American women, the positive association with risk was more pronounced among high-grade serous tumors (OR = 1.31; 95% CI = 1.01-1.71) than with all other histotypes (OR = 1.05; 95% CI = 0.75-1.47). In White women, a significant association was observed irrespective of histotype (OR = 1.33; 95% CI = 1.12-1.56 and OR = 1.38; 95% CI = 1.15-1.66, respectively). CONCLUSIONS: While genital powder use was more prevalent among African-American women, the associations between genital powder use and ovarian cancer risk were similar across race and did not materially vary by histotype. IMPACT: This is one of the largest studies to date to compare the associations between genital powder use and ovarian cancer risk, overall and by histotype, between African-American and White women.

Distinctive pattern of left-right asymmetry of ovarian benign teratomas in Chinese population: a 12-year-long cross-sectional study.

PURPOSE: Given the lack of research on the left-right asymmetry of ovarian teratoma among Chinese patients, this study aimed to determine the lateral distribution and related clinical characteristics of Chinese ovarian teratoma patients treated at a single center. METHODS: We conducted a cross-sectional study of surgical patients pathologically diagnosed with ovarian teratomas in the gynecology inpatient department of the International Peace Maternity and Child Health Hospital in Shanghai between July 2006 and July 2018. RESULTS: Of the 4417 patients with ovarian teratoma, 3835 were finally analyzed. There were 2030 (53.24%) cases of right-sided benign ovarian teratoma versus 1783 (46.76%) cases of left-sided benign teratoma (P < 0.001). The recurrence rate of benign ovarian teratoma was 4.2%; recurrence occurred more often on the left side (left vs. right = 55 vs. 45%, P = 0.033). Compared with the right-sided ovarian teratoma patients, left-sided ones had significantly high recurrence risk (OR 1.430; 95% CI 1.03-1.99). The rate of ovarian torsion in patients with ovarian mature cystic teratomas (MCTs) during intrauterine pregnancy was 3.17 versus 1.72% in non-pregnant MCT patients (P = 0.049). For those MCT patients with intrauterine pregnancy, ovarian torsion occurs more often on the right side (left vs. right = 16.67 vs. 83.33%, P = 0.028). CONCLUSION: This study confirms a distinctive right-side dominance of benign ovarian teratomas. Compared with the right side, recurrent ovarian teratomas occur more often on the left side, requiring close follow-up. Intrauterine pregnancy may increase the risk of ovarian torsion, particularly on the right side, in MCT patients.

Screening for PIK3CA mutations among Saudi women with ovarian cancer.

The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p = .023), grade (p = .001) and histological types (p = .032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.Impact statementWhat is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA.What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer.What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.

Age at diagnosis of cancer in 185delAG BRCA1 mutation carriers of diverse ethnicities: tentative evidence for modifier factors.

Germline pathogenic sequence variants (PSVs) in BRCA1 substantially increase risk for developing breast (BC) and ovarian cancer (OvC). Yet, incomplete penetrance suggests that modifier factors affect phenotypic expression of mutant BRCA1 alleles. Analysis of identical BRCA1 PSV carriers of diverse ethnicities may provide further evidence for modifier factors. Female carriers of the 185delAG BRCA1 PSV identified through high-risk clinics in Israel, and Manchester England from 1998-2018 were eligible. Data were retrieved from patients records and confirmed (in Israel) by cross referencing with the Israeli National Cancer Registry. Overall, 2503 female carriers were included: 1715 (71.4%) Ashkenazi Jews (AJ), 201 (8.3%) Iraqi Jews and 383 (15.9%) of mixed ethnicity. In 102 (4.2%) cases ethnicity could not be ascertained. Of Israeli AJ carriers 649 (37.8%), 256 (14.9%) and 62 (3.6%) were diagnosed with BC, OvC or both cancers, respectively. For the Iraqi Jews these frequencies were 76 (37.8%), 43 (21.4%), and 8 (3.98%), respectively. Age at diagnosis of BC in AJ and Iraqi Jews was 46.7 ± 12.3 years and 52.8 ± 12.2 years, respectively (p = 0.001). For OvC age at diagnosis for AJ was 53.5 ± 10.7 years and for Iraqi Jews 50.1 ± 8.8 years (p = 0.0027). No differences in these parameters were noted between English Jews (n = 110) and non-Jews (n = 32). Age at diagnosis of BC and OvC differs between AJ and Iraqi Jews who carry an identical BRCA1 PSV. This finding supports the existence of modifier factors that may be ethnic specific.

BRCA1/2 mutations and risk-reducing bilateral salpingo-oophorectomy among Latinas: The UPTAKE study.

Bilateral salpingo-oophorectomy (BSO) is a risk management approach with strong evidence of mortality reduction for women with germline mutations in the tumor suppressor genes BRCA1 and BRCA2 (BRCA1/2). Few studies to date have evaluated uptake of BSO in women from diverse racial and ethnic backgrounds who carry BRCA1/2 mutations. The objective of the UPTAKE study was to explore rates and predictors of risk-reducing BSO among Latinas affected and unaffected with breast cancer who had a deleterious BRCA1/2 mutation. We recruited 100 Latina women with deleterious BRCA1/2 mutations from community hospitals, academic health systems, community, and advocacy organizations. Women completed interviews in Spanish or English. We obtained copies of genetic test reports for participants who provided signed medical release. After performing threefold cross-validation LASSO for variable selection, we used multiple logistic regression to identify demographic and clinical predictors of BSO. Among 100 participants, 68 had undergone BSO at the time of interview. Of these 68, 35 were US-born (61% of all US-born participants) and 33 were not (77% of the non-US-born participants). Among Latinas with BRCA1/2 mutations, older age (p = 0.004), personal history of breast cancer (p = 0.003), higher income (p = 0.002), and not having a full-time job (p = 0.027) were identified as variables significantly associated with uptake of BSO. Results suggest a high rate of uptake of risk-reducing BSO among a sample of Latinas with BRCA1/2 mutations living in the US. We document factors associated with BSO uptake in a diverse sample of women. Relevant to genetic counseling, our findings identify possible targets for supporting Latinas' decision-making about BSO following receipt of a positive BRCA1/2 test.

Adherence to treatment guidelines as a major determinant of survival disparities between black and white patients with ovarian cancer.

OBJECTIVE: To evaluate whether non-adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and other factors related to treatment access contribute to racial disparities in ovarian cancer survival. METHODS: This large cohort study included patients from the National Cancer Database who were diagnosed with ovarian cancer between 2004 and 2014, with follow-up data up to 2017. The multivariable Cox regression was used to assess the effect of study variables on five-year overall survival. The proportion contributions of prognostic factors to the survival disparities were estimated using individual and sequential adjustment of these factors based on the Cox proportional hazards models. RESULTS: Of the 120,712 patients eligible for this study, 110,032 (91.1%) were whites and 10,680 (8.9%) were blacks. Black patients, compared with their white counterparts, had a lower adherence to NCCN guidelines (60.8% vs. 70.4%, respectively, P < 0.001), and a higher five-year mortality after cancer diagnosis (age- and tumor characteristics- adjusted hazard ratio: 1.22, 95% confidence interval: 1.19-1.25). Non-adherence to NCCN treatment guidelines was the most significant contributor to racial disparity in ovarian cancer survival, followed by access to care and comorbidity, each explaining 36.4%, 22.7%, and 18.2% of the racial differences in five-year overall survival, respectively. These factors combined explain 59.1% of racial survival disparities. Risk factors identified for non-adherence to treatment guidelines among blacks include insurance status, treatment facility type, educational attainment, age, and comorbidity. CONCLUSIONS: Adherence status to NCCN treatment guidelines is the most important contributor to the survival disparities between black and white patients with ovarian cancer. Our findings call for measures to promote equitable access to guideline-adherence care to improve the survival of black women with ovarian cancer.

Disparities in ovarian cancer survival at the only NCI-designated cancer center in Kansas.

BACKGROUND: This study examined the impact of geographic distance on survival outcomes for patients receiving treatment for ovarian cancer at the only NCI-designated cancer center (NCI-CC) in Kansas. METHODS: We identified ovarian cancer patients treated at the University of Kansas Cancer Center between 2010 and 2015. Demographic factors and clinical characteristics were abstracted. The main outcome measure was overall survival according to geographic distance from the institution. Kaplan Meier survival curves and Cox proportional hazard models were generated using SAS v9.4. RESULTS: 220 patients were identified. Survival analysis based on distance from the institution demonstrated that patients who lived ≤10 miles from the institution had worse overall survival (p = 0.0207) and were more likely to have suboptimal cytoreductive surgery (p = 0.0276). Lower estimated median income was also associated with a 1.54 increased risk of death, 95% CI (1.031-2.292), p = 0.0347. CONCLUSIONS: We determined that ovarian cancer survival disparities exist in our patient population. Lower rates of optimal cytoreductive surgery has been identified as a possible driver of poor prognosis for patients who lived in proximity to our institution.

Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients.

Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM's molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively (p < 0.001). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.