Number Of Ovarian Cancer Cases Research Articles

Opportunistic Salpingectomy at the Time of Laparoscopic Cholecystectomy for Ovarian Cancer Prevention: A Cost-effectiveness Analysis.

To perform a cost-effectiveness analysis to examine the utility and effectiveness of OS performed at the time of elective cholecystectomy [laparoscopic cholecystectomy (LAP-CHOL)]. OS has been adopted as a strategy to reduce the risk of ovarian cancer in women undergoing hysterectomy and tubal sterilization, although the procedure is rarely performed as a risk reducing strategy during other abdominopelvic procedures. A decision model was created to examine women 40, 50, and 60 years of age undergoing LAP-CHOL with or without OS. The lifetime risk of ovarian cancer was assumed to be 1.17%, 1.09%, and 0.92% for women age 40, 50, and 60 years, respectively. OS was estimated to provide a 65% reduction in the risk of ovarian cancer and to require 30 additional minutes of operative time. We estimated the cost, quality-adjusted life-years, ovarian cancer cases and deaths prevented with OS. The additional cost of OS at LAP-CHOL ranged from $1898 to 1978. In a cohort of 5000 women, OS reduced the number of ovarian cancer cases by 39, 36, and 30 cases and deaths by 12, 14, and 16 in the age 40-, 50-, and 60-year-old cohorts, respectively. OS during LAP-CHOL was cost-effective, with incremental cost-effectiveness ratio of $11,162 to 26,463 in the 3 age models. In a probabilistic sensitivity analysis, incremental cost-effectiveness ratio for OS were less than $100,000 per quality-adjusted life-years in 90.5% or more of 1000 simulations. OS at the time of LAP-CHOL may be a cost-effective strategy to prevent ovarian cancer among average risk women.

The Burden of Gynecologic Cancers in the UAE

There is limited published data about gynecological cancers in the UAE. The latest cancer registry data published in 2020 for the 2017 reports a total of 7% (301/4299 ) out of the total cases of all cancer among the UAE population. The most diagnosed gynecologic cancers were uterine, cervix uteri and ovarian cancer, which ranked 5th, 6th, and 8th, respectively among all female malignant cancers in the UAE. There were 111 cases of uterus cancer, which accounted for 4.93% of all cancer cases among females, diagnosed in 2017. Due to various well-structured programs in the UAE for cervical cancer prevention, including implementation of HPV vaccination for females, aged 15-26 years and screening with a pap test for women 25-65 years, regardless of their HPV vaccination status. The rate of carcinoma in situ of cervix uteri in the UAE has declined by over 50% (from 81 cases in 2015 to 38 cases in 2017). There were 70 cases of ovarian cancer, accounted for 3.11% of all cancer cases among females, diagnosed in 2017. The highest number of ovarian cancer cases has been reported in the age group of 50-54. The malignant neoplasm of cervix uteri makes up to 1.9% of the total deaths (ranked 6th), caused by cancer in the UAE population, in 2017. Currently, the gynecology cancer research in the UAE is very limited. There is a need for initiation of gynecology specific working groups to facilitate the research in this area with focus on prevention, early diagnosis, and screening specific to the UAE population.

Abstract 4623: External validation of the BOADICEA model for predicting ovarian cancer risk: The Breast Cancer Family Registry

Abstract Purpose: In the U.S., ovarian cancer is the most fatal of the gynecological cancers with an overall five-year survival rate of 47.6%. While women with a BRCA1 or BRCA2 mutation are at a much higher risk of developing ovarian cancer, mutations in these genes account for less than 50 percent of the familial aggregation of ovarian cancer. Being able to identify women at greatest risk, including those with increased familial risk without a BRCA1 or BRCA2 mutation, is critical for clinical decision-making; however, there is a lack of risk prediction models for ovarian cancer and those that do exist have modest discriminatory power. Therefore, we externally validated the BOADICEA model, a breast and ovarian cancer risk prediction model based on a woman's multigenerational family history and genetic information, for predicting ovarian cancer risk in an independent, prospective cohort of women. Methods: We used data from the Breast Cancer Family Registry (BCFR), a cohort of families with breast and ovarian cancer at baseline that have been prospectively followed. We assessed the 10-year performance of the BOADICEA model (version 3) for ovarian cancer risk overall, and by known BRCA1 or BRCA2 mutation statuses. We included women who did not have an ovarian cancer diagnosis or a bilateral oophorectomy prior to baseline, and who had sufficient data to calculate the 10-year BOADICEA risk score. We assessed model calibration using the ratio of the expected (E) to the observed (O) number of ovarian cancer cases in the cohort (E/O), and model discrimination by the concordance statistics (C-statistic) derived from the receiver operating characteristic curves. Results: There were 125 prospective ovarian cancer cases over a median of 12.3 years of follow-up among 18,534 women eligible for this analysis. For the overall cohort, the BOADICEA model was well calibrated with an E/O of 0.87, 95% confidence interval (CI) (0.70, 1.08). There was a suggestion of model underprediction in the top quartile of assigned risk (1.33% observed risk vs. 1.09% predicted risk), however it was not statistically significant (p=0.15). The C-statistic was 0.77, 95% CI (0.73, 0.82). For known BRCA1 or BRCA2 mutation carriers combined, the E/O was 0.91, 95% CI (0.63, 1.32) and the C-statistic was 0.75, 95% CI (0.67, 0.83). For non-carriers, the E/O was 0.85, 95% CI (0.65, 1.11) and the C-statistic was 0.68, 95% CI (0.59, 0.74). Conclusion: The BOADICEA model is well-calibrated in predicting ovarian cancer risk over 10 years and has good discriminatory power for women at increased familial risk of breast and ovarian cancer, with or without a known mutation in BRCA1 or BRCA2. Therefore, BOADICEA has clinical utility for evaluating ovarian cancer risk based on a woman's family cancer history and genetic information. Citation Format: Jennifer S. Ferris, Jeanine M. Genkinger, Mary Beth Terry, Yuyan Liao, Robert J. MacInnis, Irene L. Andrulis, Saundra S. Buys, Mary B. Daly, Esther M. John, John L. Hopper. External validation of the BOADICEA model for predicting ovarian cancer risk: The Breast Cancer Family Registry [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4623.

Cost-effectiveness of opportunistic salpingectomy vs tubal ligation at the time of cesarean delivery

Removal of the fallopian tubes at the time of hysterectomy or interval sterilization has become routine practice to prevent ovarian cancer. While emerging as a strategy, uptake of this procedure at the time of cesarean delivery for pregnant women seeking permanent sterilization has not been widely adopted due to perceptions of increased morbidity and operative difficulty with a lack of available data in this setting. We sought to conduct a cost-effectiveness analysis comparing strategies for long-term sterilization and ovarian cancer risk reduction at the time of cesarean delivery, including bilateral tubal ligation, opportunistic salpingectomy, and long-acting reversible contraception. A decision-analytic and cost-effectiveness model was constructed for pregnant women undergoing cesarean delivery who desired permanent sterilization in the US population, comparing 3 strategies: (1) bilateral tubal ligation, (2) bilateral opportunistic salpingectomy, and (3) postpartum long-acting reversible contraception. This theoretic cohort consisted of 110,000 pregnant women desiring permanent sterilization at the time of cesarean delivery and ovarian cancer prevention at an average of 35 years who were monitored for an additional 40 years based on an average US female life expectancy of 75 years. The primaryoutcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured as quality-adjusted life years. Secondary outcomes included: the number of ovarian cancer cases and deaths, procedure-related complications, and unintended and ectopic pregnancies. The 1-, 2-, and 3-way and Monte Carlo probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set at $100,000. Both bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery have favorable cost-effectiveness ratios. In the base case analysis, salpingectomy was more cost-effective with an incremental cost-effectiveness ratio of $23,189 per quality-adjusted life year compared to tubal ligation. Long-acting reversible contraception after cesarean was not cost-effective (ie, dominated). Although salpingectomy and tubal ligation were both cost-effective over a wide range of cost and risk estimates, the incremental cost-effectiveness ratio analysis was highly sensitive to the uncertainty around the estimates of salpingectomy cancer risk reduction, risk of perioperative complications, and cost. Monte Carlo probabilistic sensitivity analysis estimated that tubal ligation had a 49% chance of being the preferred strategy over salpingectomy. If the true salpingectomy risk of perioperative complications is >2% higher than tubal ligation or if the cancer risk reduction of salpingectomy is <52%, then tubal ligation is the preferred, more cost-effective strategy. Bilateral tubal ligation and bilateral opportunistic salpingectomy with cesarean delivery are both cost-effective strategies for permanent sterilization and ovarian cancer risk reduction. Although salpingectomy and tubal ligation are both reasonable strategies for cesarean patients seeking permanent sterilization and cancer risk reduction, threshold analyses indicate that the risks and benefits of salpingectomy with cesarean delivery need to be better defined before a preferred strategy can be determined.

Abstract A42: TR3/NR4A1 as a therapeutic target for ovarian cancer

Abstract Background: A key clinical challenge in ovarian cancer is identifying new targets and strategies to treat recurrent and platinum-resistant disease. We and others have previously linked the nuclear orphan receptor NR4A1/Nur77 (TR3) to multiple malignancies; however, the role of TR3 in cancer is complex. In ovarian cancer cells, multiple chemotherapeutic agents stimulate translocation of TR3 to mitochondria to induce apoptosis, whereas nuclear TR3 is a transcription factor with progrowth and prosurvival effects. Moreover, the prognostic value of TR3 expression in ovarian tumors is not fully defined. Two prior reports had contradictory findings, with both positive and negative associations with ovarian cancer survival observed. Objective: We undertook this study to test the therapeutic potential of inhibiting TR3 in ovarian cancer cells and to clarify the prognostic value of TR3 expression in ovarian tumors. Methods: In a panel of established ovarian cancer cell lines, including cisplatin-resistant A2780CP20 and NCI/ADR-RES and their respective isogenic counterparts, A2780PAR and OVCAR-8, we inhibited TR3 function using established chemical antagonists, 1,1-bis(3′-indolyl)-1-(p-methoxyphenyl)methane, 3,3′-[(4-methoxyphenyl)methylene]bis-1H-indole, which is metabolized to an active p-hydroxyphenyl form in cells (C-DIM), and ethyl-2-(2,3,4-trimethoxy-6-(1-octanoyl)phenyl)acetate (TMPA), as well as two distinct siRNAs that targeted TR3. Cell growth was assessed in sulforhodamine B assays; apoptosis was measured by Western blot analysis of cleaved caspase-3 expression. A luciferase reporter plasmid with three consensus TR3 binding sites was used to measure TR3 transactivation and DNA binding activity. In ovarian tumors, TR3 was measured by immunohistochemistry (IHC) on 203 formalin-fixed, paraffin-embedded tissue samples from the Vanderbilt University Medical Center Tissue Repository for Ovarian Cancer (TROC) with linked clinical data abstracted from electronic medical records. TR3 staining intensity (1: weak; 2: moderate; 3: strong) and percent of positive nuclei (0-100) were multiplied to yield an H score. Associations with progression-free survival (PFS) and overall survival (OS) were quantified by hazards ratios (HR) and 95% confidence intervals (CI) from multivariable proportional hazards regression. Results: In our ovarian cancer cell line panel, C-DIM and TMPA induced concentration-dependent decreases in cell growth and TR3 transactivation and stimulated apoptosis. The magnitude of growth inhibition and apoptosis induction in cisplatin-resistant cells was strikingly similar to that seen in isogenic counterparts. Cells with high basal TR3 expression (OVCAR-3 and OVCAR-4) showed greater responses to TR3 inhibitors than those with low TR3 expression (SKOV-3). These effects were mimicked in cells transfected with TR3-targeting siRNA compared to non-targeting siRNA-transfected controls. In 203 TROC cases, TR3 expression lower than the median (&amp;lt;153.6) was more likely among later-stage, higher-grade, type II tumors, with suboptimal cytoreduction and platinum resistant disease. Higher TR3 was associated with better OS (HR: 0.52, 95% CI: 0.37-0.74) in unadjusted analyses. However, after adjustment for prognostic covariates, higher TR3 was associated with significantly shorter PFS (HR: 2.35, 95% CI: 1.29-4.28). Conclusions: Our current results reconcile the discrepancy between prior TR3 reports, as associations differed due to confounding by clinical covariates. Worse outcomes among cases with high TR3 expression are supported by new experimental evidence showing reduced ovarian cancer cell growth and survival following TR3 inhibition. Our findings support further development of TR3 inhibition as a novel therapeutic approach, which could benefit a large number of ovarian cancer cases with recurrent and platinum-resistant disease. Citation Format: Alicia Beeghly-Fadiel, Dajah Chase, Johnathan Cooks, Marta Crispens, Dineo Khabele, Andrew J. Wilson. TR3/NR4A1 as a therapeutic target for ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr A42.

Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

The number of ovarian cancer cases is predicted to rise by 14% in Europe and 55% worldwide over the next 2 decades. The current absence of a screening program, rising drug/treatment costs, and only marginal improvements in survival seen over the past 30 years suggest the need for maximizing primary surgical prevention to reduce the burden of ovarian cancer. Primary surgical prevention through risk-reducing salpingo-oophorectomy (RRSO) is well established as the most effective method for preventing ovarian cancer. In the UK, it has traditionally been offered to high-risk women (>10% lifetime risk of ovarian cancer) who have completed their family. The cost-effectiveness of RRSO in BRCA1/BRCA2 carriers older than 35 years is well established. Recently, RRSO has been shown to be cost-effective in postmenopausal women at lifetime ovarian cancer risks of 5% or greater and in premenopausal women at lifetime risks greater than 4%. The acceptability, uptake, and satisfaction with RRSO at these intermediate-risk levels remain to be established. Prospective outcome data on risk-reducing salpingectomy and delayed-oophorectomy for preventing ovarian cancer is lacking, and hence, this is best offered for primary prevention within the context and safe environment of a clinical trial. An estimated 63% of ovarian cancers occur in women with greater than 4% lifetime risk and 53% in those with 5% or greater lifetime-risk. Risk-reducing salpingo-oophorectomy can be offered for primary surgical prevention to women at intermediate risk levels (4%-5% to 10%). This includes unaffected women who have completed their family and have RAD51C, RAD51D, or BRIP1 gene mutations; first-degree relatives of women with invasive epithelial ovarian cancer; BRCA mutation-negative women from high-risk breast-and-ovarian cancer or ovarian-cancer-only families. In those with BRCA1, RAD51C/RAD51D/MMR mutations and the occasional families with a history of ovarian cancer in their 40s, surgery needs to be considered at younger than 45. In other moderate-risk gene mutation carriers and those with polygenic risk, RRSO needs be considered at 50. There is need for establishment/expansion of well-defined pathways to increase clinical access to RRSO. It is time to lower the risk threshold for RRSO to enable introduction of a targeted primary prevention approach, which could significantly impact the future burden of ovarian cancer.

Commentary on changing the risk threshold for surgical prevention of ovarian cancer.

Ovarian cancer (OC) remains a lethal disease and a major cause of deaths from gynaecological cancer particularly in western countries. Despite advances in treatment, there have been only marginal improvements in survival rates over the last 30years. Additionally, the number of OC cases in the UK is estimated to increase by 27-45%, which translates to a 15% rise in the incidence rate by 2035.(1) A national OC screening programme is unavailable as this has not yet shown a conclusive mortality benefit.(2) Hence, primary prevention continues to be the cornerstone in reducing the burden of OC and improving health outcomes. This is essential to achieve long term transformational change and cost-efficiencies in our health-system. Its importance is amplified by current economic restraints, with a ~2.4% funding shortfall reported in the UK National-Health-Service (NHS). This article is protected by copyright. All rights reserved.

BRCA-like classification in ovarian cancer: Results from the AGO-TR1-trial.

5546 Background: BRCA associated cancers show a distinct pattern of genomic gains and losses that is associated with impaired repair of DNA double-strand breaks via homologous recombination (HR). We investigated whether BRCA1- and BRCA2-like classifiers could predict BRCA1 and BRCA2 mutation status in ovarian cancer. In addition, we explored whether promoter hypermethylation or mutations in other genes involved in DNA repair associate with a BRCA-like profile in ovarian cancer. Methods: The AGO-TR1 cohort study (NCT02222883 ) enrolled 525 consecutive patients with primary (PR) and platinum sensitive relapsed (RE) ovarian cancer to perform paired mutational analysis of germline and tumor tissue. We performed mutation panel sequencing, BRCA1 promoter hypermethylation and low-coverage whole genome sequencing to classify samples as BRCA1-like or BRCA2-like in 298 ovarian cancer samples (PR: n = 159, RE: n = 139). Results: A BRCA-like profile was observed in 58.1% of the samples without germline or somatic mutation in BRCA1/2 (n = 179; BRCA1-like: n = 26, BRCA2-like: n = 23, BRCA1- and 2-like: n = 55). There was no significant difference between PR- and RE-cases (54.5% vs 61.3%). 64 of 70 BRCA1 germline mutation carriers could be identified by the BRCA1-like classifier (sensitivity: 0.91). The BRCA2-like classifier identified BRCA2 germline mutation carrier with a sensitivity of 0.71 (17 of 24). The complementary use of both classifiers led to the detection of 22 of 25 somatic mutations in BRCA1 (16/16) or - 2 (6/9). Remarkably, 12 of 13 tumor samples from germline RAD51C mutation carriers were recognized by the BRCA1-like classifier (sensitivity: 0.92). No correlation of PALB2 mutation status (n = 7) with BRCA-like profile was observed. Of 28 tumor samples with a BRCA1 promoter hypermethylation 26 had a BRCA1-like profile (sensitivity: 0.93). Conclusions: A high number of ovarian cancer cases display a BRCA-like profile. Mutations (germline and somatic) in BRCA1, BRCA2, RAD51C as well as BRCA1 hypermethylation strongly associate with a BRCA-like profile and can explain 146 of 212 cases. Future studies will investigate whether the classifiers identify patients who benefit from HR-deficiency directed approaches beyond the BRCA mutation status. Clinical trial information: NCT02222883.

Abstract B35: Ovarian cancer incidence projections in the United States: Expected increases through 2030.

Abstract Background: Several reports have shown that age-standardized ovarian cancer rates are decreasing in recent years in the United States. While these reported rates are useful to compare trends across certain groups, they do not always accurately convey the burden of ovarian cancer, nor do they provide information on the actual numbers of ovarian cases diagnosed each year. Since age is the greatest risk factor for ovarian cancer, and the older population of the Unites States is growing, the accurate assessment of future ovarian cancer trends is important in order to plan for clinical care needs and allocate resources effectively. Objective: To assess future trends in the United States ovarian cancer burden by projecting the number of new cases of ovarian and fallopian tube cancer cases diagnosed through the year 2030. Methods: We used observed incidence data from 1982-2011 from the SEER program, and population projections based on the 2010 US Census to predict ovarian and fallopian tube cancer cases and rates through 2030. Cases of both ovarian and fallopian tube cancers were included to account for misclassification that often occurs between the two cancer sites and also because some ovarian cases are thought to originate in the fallopian tube. Predictions were made using age-period-cohort regression models implemented in the Nordpred software. Results: The number of ovarian cancer cases is estimated to increase from 23,215 in 2012 to 27,666 in 2030, for a 19.2% total increase in new cases of ovarian cancer in 2030. Fallopian tube cancer cases are expected to increase from 1,621 in 2012 to 3,686 in 2030. Together, 31,352 cases of ovarian and fallopian tube cancers are projected to be diagnosed in 2030, for an overall expected increase of 26.2% for these cancers. Discussion: Given the expected increase in cancer cases, prioritizing resources for ovarian cancer control is warranted. Continued training and outreach of gynecologic oncologists to ensure ovarian cancer patients receive optimal treatment is necessary. Systems changes that ensure referral and accessibility to gynecologic oncologists are also needed. Additional research into genetic and other factors that predispose individuals to ovarian cancer, and the continued characterization of symptoms may help to identify cases earlier, potentially resulting in more treatment options for ovarian cancer patients. Citation Format: Sherri L. Stewart, Trevor D. Thompson, Hannah K. Weir, Sun Hee Rim. Ovarian cancer incidence projections in the United States: Expected increases through 2030. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B35.

Costs and Benefits of Opportunistic Salpingectomy as an Ovarian Cancer Prevention Strategy

Evidence accumulated over the past decade suggests that the majority of ovarian cancers arise in the fallopian tube and not the ovary. This led to the recommendation that opportunistic salpingectomy be offered as an elective concurrent procedure for premenopausal women at average risk of ovarian cancer who undergo either hysterectomy for benign gynecologic conditions or surgical sterilization. It has been estimated that opportunistic salpingectomy could reduce the ovarian cancer risk by 20% to 40% over the next 20 years. There are few hard data, however, on the long-term risks and benefits associated with this procedure. Because a clinical trial is not feasible, a population-based cohort study is essential to establish the long-term risks, benefits, and cost-effectiveness of opportunistic salpingectomy. Such a cohort study would take many years to yield results; more timely data on the likely costs and benefits of this strategy could be obtained from a decision analytic model. The aim of this study was to conduct a cost-effectiveness analysis of opportunistic salpingectomy as an ovarian cancer prevention strategy in the general population. A Markov Monte Carlo simulation model was used to estimate the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of premenopausal Canadian women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization as permanent contraception. Three strategies were compared: hysterectomy alone, hysterectomy with salpingectomy, and hysterectomy with bilateral salpingo-oophorectomy (BSO). The main outcome measure was the incremental cost-effectiveness ratio. Effectiveness was calculated in terms of average years of life expectancy gain. Multiple sensitivity analyses accounted for uncertainty around various parameters, including treatment costs, age at surgery, and estimates of risk reduction attributable to salpingectomy. The number of ovarian cancer cases associated with each strategy was estimated in the simulation model. The model predicted that salpingectomy with hysterectomy would be less costly ($11,044 ± $1.56) and more effective (21.12 ± 0.02 years) than either hysterectomy alone ($11,207 ± $29.81, 21.10 ± 0.03 years) or BSO ($12,627 ± $13.11, 20.94 ± 0.03 years), respectively. The model also predicted that salpingectomy for sterilization would be marginally more costly than tubal ligation ($9720 ± $3.74 vs $9339 ± $26.74) but more effective (22.45 ± 0.02 vs 22.43 ± 0.02 years of life expectancy), with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Results were stable over a wide range of treatment costs and estimates of risk reduction. In the Monte Carlo simulation model, salpingectomy reduced the risk of ovarian cancer by 38.1% (95% confidence interval, 36.5%–41.3%) compared with hysterectomy alone and 29.2% (95% confidence interval, 28.0%–31.4%) compared with tubal ligation. This analytic model shows that opportunistic salpingectomy with hysterectomy for benign conditions has the potential to decrease ovarian cancer risk at acceptable cost and that salpingectomy is a cost-effective alternative to use of tubal ligation for sterilization. These findings suggest that prophylactic salpingectomy should be considered in all women undergoing these procedures.

An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study.

Background:Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents.Methods:We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study.Results:Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81–1.01), in general there was no evidence for miscalibration.Conclusion:Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.

Epidemiology of epithelial ovarian cancer, a single institution-based study in India

Background: Ovarian cancer is the leading cause of mortality among all cancers of female genital tract in countries where effective cervical cancer screening program exists. As the world's population ages, remarkable increase in the total number of ovarian cancer cases are expected. This is preliminary epidemiological study to decide priorities in ovarian cancer research. Materials and Methods: A retrospective study was conducted with primary epithelial ovarian cancer cases registered in J. K. Cancer Institute, Kanpur (Uttar Pradesh), from 2007 to 2009. Patients' age at diagnosis, clinical feature, parity of patients, tumor histological type, Federation of Gynecology and Obstetrics stage, chemotherapy regimens, and overall survival data were collected and analyzed. Results: One hundred and sixty-three cases of primary ovarian epithelial cancer were analyzed. Patients' mean age at diagnosis was 55.98 ± 9.24 (median = 55). Serous adenocarcinoma (49.69%) was the most prevalent type of histopathology followed by endometroid (19.1%), mucinous (10.42%) and clear cell (4.29%). Combination of taxane and platin was most commonly used first line regimen in newly diagnosed as well as in relapsed patients post 1 year. Survival was not significantly different in various histopathology (log-rank P = 0.7406), but advancing stage demonstrated gradually poor survival (log-rank P Conclusion: Research efforts should be in the direction to find early diagnostic and effective screening tools as well as better therapeutic approaches for advanced epithelial ovarian cancer.

Incidence rate of ovarian cancer cases in Saudi Arabia: an observational descriptive epidemiological analysis of data from Saudi Cancer Registry 2001-2008.

PurposeThis study provides descriptive epidemiological data, such as the percentage of cases diagnosed, crude incidence rate (CIR), and age-standardized incidence rate (ASIR) of ovarian cancer in Saudi Arabia from 2001–2008.Patients and methodsA retrospective descriptive epidemiological analysis of all ovarian cancer cases recorded in the Saudi Cancer Registry (SCR) from January 2001–December 2008 was performed. The data were analyzed using descriptive statistics, analysis of variance tests, Poisson regression, and simple linear modeling.ResultsA total of 991 ovarian cancer cases were recorded in the SCR from January 2001–December 2008. The region of Riyadh had the highest overall ASIR at 3.3 cases per 100,000 women, followed by the Jouf and Asir regions at 3.13 and 2.96 cases per 100,000 women. However, Hail and Jazan had the lowest rates at 1.4 and 0.6 cases per 100,000 women, respectively. Compared to Jazan, the incidence rate ratio for the number of ovarian cancer cases was significantly higher (P<0.001) in the Makkah region at 6.4 (95% confidence interval [CI]: 4.13–9.83), followed by Riyadh at 6.3 (95% CI: 4.10–9.82), and the eastern region of Saudi Arabia at 4.52 (95% CI: 2.93–6.98). The predicted annual CIR and ASIR for ovarian cancer in Saudi Arabia could be defined by the equations 0.9 + (0.07× years) and 1.71 + (0.09× years), respectively.ConclusionWe observed a slight increase in the CIRs and ASIRs for ovarian cancer in Saudi Arabia from 2001–2008. Riyadh, Jouf, and Asir had the highest overall ASIR, while Jazan and Hail had the lowest rates. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases. Further analytical studies are required to determine the potential risk factors of ovarian cancer among Saudi women.

Surgical practice of UK gynaecological oncologists in the treatment of primary advanced epithelial ovarian cancer (PAEOC): A questionnaire survey

ObjectiveTo assess the routine surgical practices of consultant gynaecological oncologists (CGOs) in the United Kingdom in their management of primary advanced (FIGO stages III and IV) epithelial ovarian cancer (PAEOC). MethodsThe same anonymised questionnaire was sent twice to all consultant gynaecological oncologists (CGOs) working in the UK. The questions enquired about surgical practice of the previous calendar year and the respondents were asked to describe their usual or typical management of patients with PAEOC. Results45 of 85 CGOs responded (53%). The mean number of ovarian cancer cases operated on by an individual surgeon was 47 (range 6–100). 6% of the surgeons never perform pelvic lymphadenectomy, and 22% of the surgeons never perform para-aortic lymphadenectomy in the primary surgery (PS) group, compared to 8% and 30% in the neoadjuvant chemotherapy (NAC) group. In the PS group 17% of the respondents perform pelvic lymphadenectomy routinely (80% or more of patients) compared to 11% of the respondents in the NAC group. The rates of bowel surgery and surgery for upper abdominal disease were highly variable. The average operating time per case was less than 3h in 78% of the respondents. ConclusionsThe mean operating times, caseload, and types of procedure undertaken in the management of advanced ovarian cancer provide compelling evidence that in many UK cancer centres the surgical goal has not been complete cytoreduction. These data have implications for the centralisation of surgical services, subspecialty training, and the lower survival of UK patients compared to other comparable countries.

BRCA1 gene mutations may explain more than 80% of excess number of ovarian cancer cases after breast cancer – a population based study from the Western Sweden Health Care region

Aim. In a previous cohort study, we showed that there was a significant variation in the frequency of ovarian cancer after having breast cancer in Sweden, with the highest risk occuring in the Western region. The present study aimed to evaulate whether the high prevalence of the founder mutation BRCA1 3171ins5 may explain the excess number of ovarian cancer. Method. Among more than 26 000 women with breast cancer in the Western Swedish Health Care Region, 159 cases were subsequently diagnosed with ovarian cancer, whereas the expected number was 96. Archived tissue material was analysed for six common Scandinavian BRCA1 and BRCA2 gene mutations. Results. The excess number of cases was 63 (95% CI 47–77), based on person-years at risk and national incidence rates of ovarian cancer. A BRCA1 gene mutation was detected in 33 cases corresponding to 52% of the excess number. The founder mutation, BRCA1 3171ins5, was detected in 44% of the excess number. The identified mutations decreased from 45% in women less than 50 years of age at follow-up to 14% at 60+ years at follow-up. There was no obvious decrease in mutation frequency by excess numbers with age. Age at follow-up and first-degree relatives with breast and/or ovarian cancer were the best predictors of a mutation in this material. Conclusion. The founder mutation, BRCA1 3171ins5, explains the excess of ovarian cancer after breast cancer in the region. From the relative frequency of the studied mutations found at the cancer genetic counselling clinic, it is estimated that BRCA1 gene mutations are associated with about 80–85% of the excess cases. This means that a negative screening for these mutations in similar cases may have a predictive value and could strongly reduce the risk of ovarian cancer in relatives.

Reproductive and Hormonal Factors, and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Results from the International BRCA1/2 Carrier Cohort Study

Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies. We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework. There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions. The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population.

Offspring of Women Exposed In Utero to Diethylstilbestrol (DES)

Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice. We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters. Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES. Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.

Coffee Consumption Is Not Associated with Ovarian Cancer Incidence

Coffee contains many substances that could conceivably influence the risk of ovarian cancer. In a meta-analysis of the crude data of seven case-control studies of coffee consumption and ovarian cancer published before 1990, the combined odds ratio was 1.3 [95% confidence interval (95% CI), 1.1-1.5]