Risk Of Ovarian Cancer In Women Research Articles

Abstract A006: Disparities, social determinants of health, and ovarian cancer: predicting ovarian cancer using sociodemographic information and comorbidities as risk factors

Abstract Introduction In this study, we aimed to identify associations between ovarian cancer (OC) and patient information, including demographics and comorbidities in order to increase awareness of OC risk factors and the ways in which disparities affect individual risk. Methods Administrative data analysis was performed using Florida state inpatient data collected by the Healthcare Cost and Utilization Project in 2012. Demographic variables included age, race, insurance type, and income level. Comorbidities included hypothyroidism, diabetes, hysterectomy, obesity, alcohol abuse, and drug abuse. For each variable, descriptive and logistic regression analyses were performed using SAS software and confirmed with SPSS software to determine frequencies within binary OC outcomes and calculate associations. Results Descriptive analysis revealed that OC was most frequent in white women (73.47%) over 65 (50.17%), who were Medicare beneficiaries (57.00%) within the second quartile of annual income ($38,000-$48,000) (30.71%). Most OC patients did not have any comorbidities. Logistic regression analysis revealed higher risk of OC in women over 65 compared to younger women (OR= 4.277; 95% CI= 3.585-5.103). Black women had reduced odds of OC compared to White women (OR=0.790; 95% CI= 0.693-0.900). Privately insured women had higher odds of OC compared to women with Medicare (OR= 1.426; 95% CI= 1.245-1.634). The risk of OC was reduced in patients in the first, second, and third quartiles of annual income when compared to the highest quartile of annual income (OR= 0.606; 95% CI= 0.527-0.698, OR= 0.618; 95% CI= 0.537-0.710, OR= 0.644; 95% CI= 0.557-0.743, respectively). The risk of OC was increased in women with hypothyroidism (OR= 1.083; 95% CI= 1.021-1.148), diabetes (OR= 1.134; 95% CI= 0.973-1.331), and women who had a hysterectomy (OR= 18.543; 95% CI= 15.262-22.530), compared to those without. Odds of OC were significantly reduced in women with obesity (OR= 0.574; 95% CI= 0.503-0.654) compared to those without. Women who abused alcohol or drugs had lower odds of OC than those who did not (OR= 0.296; 95% CI= 0.205-0.426, OR= 0.280; 95% CI= 0.205-0.382, respectively). Conclusions This study identifies OC risk factors and highlights differences in the prevalence and risk of OC between women of different sociodemographic groups and between women with and without various comorbidities. Groups with socioeconomic privilege were at higher risk of OC. Financial stability and access to healthcare increase the likelihood of receiving a diagnosis, suggesting potential detection bias. Decreased risk of OC was observed in patients with stigmatized comorbidities such as obesity and substance abuse disorders. Under-investigation of symptoms is common in patients with these conditions, leading to underdiagnosis. Health and socioeconomics are inextricable, so it is necessary to understand the relationship between these aspects of patient health and OC to more accurately assess individual risk. Citation Format: Anna E. Langston, Zahra Bahrani-Mostafavi. Disparities, social determinants of health, and ovarian cancer: predicting ovarian cancer using sociodemographic information and comorbidities as risk factors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A006.

Caregiver burden and risk of epithelial ovarian cancer in the Nurses' Health Studies.

Psychosocial stress may increase ovarian cancer risk and accelerate disease progression. We examined the association between caregiver burden, a common stressor, and risk of epithelial ovarian cancer. We prospectively followed 67,724 women in the Nurses' Health Study (NHS; 1992-2012) and 70,720 women in the NHSII (2001-2009) who answered questions on informal caregiving (i.e., caregiving outside of work). Women who reported no informal caregiving were considered non-caregivers while, among women who provided care outside of work, caregiver burden was categorized by time spent caregiving and perceived stress from caregiving. For the 34% of women who provided informal care for ≥15 hours per week, 42% described caregiving as moderately to extremely stressful. Pooled multivariate analyses indicated no difference in ovarian cancer risk for women providing ≥15 hours of care per week compared to non-caregivers (hazard ratio (HR)=0.96; 95% confidence interval (CI): 0.79-1.18), and no association was evident for women who reported moderate or extreme stress from caregiving compared to non-caregivers (HR=0.96; 95% CI: 0.75-1.22). Together with prior work evaluating job strain and ovarian cancer risk, our findings suggest that, when evaluating a stressor's role in cancer risk, it is critical to consider how the stressor contributes to the overall experience of distress.

Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.

Abdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity. Female C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated. While limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this 'genetic fingerprint' is important for ovarian metastases to the OFB. In accordance with the 'seed and soil' theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.

The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk.

One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk. In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L). Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83-1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11-0.98) and clear cell (4.74, 1.39-16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81-1.86), but not CRP≤3.0 mg/L (0.83, 0.66-1.05). Other associations did not vary across CRP categories. Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions. This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.

Serial monitoring of ovarian cancer risk in women with adnexal mass.

e17608 Background: Monitoring of ovarian malignancy risk in indeterminate masses is typically done using TVUS and other clinical factors. No biomarkers are available to assist physicians in clinical management of benign or indeterminate adnexal mass either on initial visit or in follow-up. We recently characterized the clinical performance of a deep neural network-derived multivariate index assay (MIA3G) [1] to assess ovarian malignancy risk in retrospective and prospectively collected multi-site clinical studies. Here we present data on MIA3G serial follow-up to monitor ovarian cancer risk in women presented with adnexal mass from the prospective studies. Methods: Data are presented from ongoing multisite clinical studies in which total 924 patients presented with adnexal masses were enrolled. Follow-up visits, scheduled at clinician’s discretion, may have included imaging and blood collection. Specimens were processed for serum and run on a clinical analyzer. MIA3G score from 0-10 was calculated using seven serum biomarkers coupling with patient age and menopausal status based on previously published neural network-based algorithm. MIA3G with NPV of 99.7% (CI:99.2–99.9) was used to risk stratify the patient with an adnexal mass into low probability of malignancy or indeterminate with a validated cut off at 5.0. For this analysis, MIA3G scores were binned into the following Zones: I (0-2.49), II (2.50 -4.99) and II (5.00-10.00). Results: Of 924 enrolled patients, 538 patients had completed clinical and biomarker data on initial study draw. Of these, 145 had at least one follow-up test and 31 had at least two follow-up test. Median duration to first follow-up test was 108 d (~3.6 mon), and median duration to second follow-up test was 272 d (~9.1 mon). Follow-up in 3 MIA3G score zones at the 0 -3.6 and 3.6 - 9.1 mon interval consistently showed 88% patients within zone I remained unchanged, whereas 12% of patients moved to zones II and III. In the 0 - 3.6 mon interval, the median change in MIA3G score from I to II was 2.25 (n = 9, range 0.54 - 3.52) and from I to III was 5.92 (n = 8, range 5.08-7.62 ). In the 3.6 - 9.1 mon testing interval, the median change in MIA3G score from zone I to II was 3.11 (n = 2, range 2.75 to 3.46) and the single patient change from I to III was 6.89. Across both testing intervals, 17%-50% of patients in zone II remain unchanged while approximately 25% patients had score increase to zone III. Importantly, 50% of patients in zone III remained unchanged in the absence of clinical intervention whereas 50% had MIA3G score reduction in association with clinical management. Conclusions: These results indicate that i) the serial follow-up with MIA3G is recommended to monitor the clinical status of the adnexal mass every 3 months, ii) MIA3G score changes of > 2.25 suggest clinical follow-up, and finally iii) the MIA3G is a suitable tool for the effectiveness of clinical management of adnexal mass. [1]: DOI 10.3389/fmed.2023.1102437.

Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium.

Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Risk of ovarian cancer in women who give birth after assisted reproductive technology (ART)-a registry-based Nordic cohort study with follow-up from first pregnancy.

There is concern that assisted reproductive technology (ART) may increase ovarian cancer risk, but previous studies are inconclusive. We compared ovarian cancer risk for women who gave birth after ART vs natural conception. Through linkage of nationwide registry data, we followed 3,303,880 initially nulliparous women in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015) from first pregnancy ≥22 weeks to ovarian cancer, emigration, death or end of follow-up (2014/2015). We estimated hazard ratios (HRs), adjusting for age, parity, maternal birth year and country, and for body mass index and smoking in subsamples. Mean age at first birth was 27.7 years. During a mean follow-up of 14.4 person-years, 2683 participants (0.08%) developed ovarian cancer; 135 after ART and 2548 after natural conception only (incidence rates 11.6 and 5.5 per 100,000 person-years, respectively). The risk was higher for women who ever gave birth after ART (HR 1.70, 95% confidence interval 1.42-2.03) compared to natural conception. Associations were stronger for conventional in vitro fertilisation than for intracytoplasmic sperm injection. Among parous women, ART-conception was associated with a higher risk of ovarian cancer than natural conception. Further studies should decipher whether this is causal or confounded by infertility or other factors.

The clinical features and management of Lynch syndrome-associated ovarian cancer.

Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, characterized by mutations in mismatch repair genes and autosomal dominant inheritance. Women with LS have an additional increased risk of gynecologic malignancies, including endometrial cancer (EC) and ovarian cancer (OC). Compared with EC, OC is relatively under investigation. This review thoroughly summarizes the current clinical evidence of surveillance, screening, and prevention strategies, and describes the molecular and clinical characteristics of LS-associated OC. An electronic search from databases of PubMed and Google Scholar was carried out using key words pertaining to Lynch syndrome and ovarian cancer. A review of the literatures including review articles, experimental, and observational studies published between 2000 and 2021 was conducted. The lifetime risk of OC in women with LS of MLH1, MSH2, and MSH6 mutations is approximately 7%, with the median age at onset being 46 years, 10-15 years earlier than that in sporadic cases. Histologically, LS-associated OCs are primarily endometrioid (40%), high-grade (25%), and low-grade (11%) serous, or clear cell (6%) in nature. Eighty-five percent of patients are diagnosed at an early stage, presenting with a good prognosis at 84% 5-year survival. Optimal screening strategies for OC in LS are controversial; combined screening of patients' clinical and family history, immunohistochemical analysis, and microsatellite instability testing for mismatch repair deficiency have been proven efficient. The clinical features were different between ovarian cancer in Lynch syndrome and sporadic cases. More research are needed for a greater understanding of the prevention and medical treatment of LS-associated OC.

Nitrogen-based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older.

BackgroundThere are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype.MethodsWe conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia’s universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression.ResultsEver use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes.ConclusionUse of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.

Serum-based assay for adnexal mass risk of ovarian malignancy.

5551 Background: A Deep learning neural network was developed to assess ovarian cancer risk in women presenting with adnexal mass into risk categories. The algorithm shows potential to improve on the performance of CA-125 as the standard biomarker to monitor women as a clinical management metric to trace increased risk of malignancy. Methods: Serum specimens from an enriched biobank (N = 2688) were collected during previous clinical studies from women presenting with an adnexal mass at risk of ovarian cancer. Protein biomarker data from these specimens were used to develop a novel neural network for binary stratification of ovarian cancer risk assessment. These specimens were divided between training and testing data sets using 5-fold cross validation during training. A randomized, separate sample set was withheld from use in training and testing the algorithm for independent validation purposes. As algorithm inputs seven biomarkers are used in the network: cancer antigen 125, human epididymis protein, beta-2 microglobulin, apolipoprotein A-1, transferrin, transthyretin, and follicle stimulating hormone. In addition to these biomarkers, the patient’s age and menopausal status are used. Menopause was defined as the absence of menses for ≥12 months. The algorithm uses supervised learning with known histopathology diagnoses as the labels for training. The algorithm is a classification deep feedforward neural network. The neural network is regularized using node dropout to reduce overfitting. The final layer of the neural network has two nodes and uses the softmax function to assign a binary classification of low or high-risk of malignancy. Results: Algorithm performance metrics are also shown comparing predicted results from the algorithm to the known malignancy diagnoses. The performance metrics are also compared below to the standard of care biomarker test, cancer antigen 125 (CA125), reporting increased sensitivity by 26.1%, and failure to reject the null hypothesis of equivalent specificity. Conclusions: The algorithm detected 91% of malignancies in the independent validation data. This high sensitivity in malignancy detection paired with the failure to reject the null hypothesis of equivalent specificity (Pearson’s chi-squared test p-value of 0.281) and negative predictive value (NPV) suggest the algorithm could be used two-fold. First, surgical referral to gynecological oncologists for women classified in the high-risk cohort. The second as a goal with future clinical validation, is that women with a low risk of malignancy might be able to delay surgery and enter into a serial monitoring clinical management care pathway.[Table: see text]

What happens after menopause? (WHAM): A prospective controlled study of depression and anxiety up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy

ObjectiveRisk-reducing bilateral salpingo-oophorectomy (RRBSO) substantially reduces ovarian cancer risk in women with pathogenic gene variants and is generally recommended by age 34–45 years. Natural menopause is a vulnerable period for mood disturbance, but the risk of depression and anxiety in the first 12 months after RRBSO and potential modifying effect of hormone therapy are uncertain. MethodsProspective controlled observational study of 95 premenopausal women planning RRBSO and a Comparison group of 99 premenopausal women who retained their ovaries,- 95% of whom were at population level risk of ovarian cancer. Clinically significant symptoms of depression and anxiety were measured using standardised instruments at baseline, 3, 6 and 12 months. Chi-square tests and adjusted logistic regression models compared differences between groups. ResultsBaseline symptoms and previous depression or anxiety did not differ between groups. At 3 months after RRBSO clinically significant depressive symptoms were doubled (14.5% vs 27.1%, p = 0.010), which persisted at 12 months. Depressive symptoms were stable in comparisons. At 3 months after RRBSO, clinically significant anxiety symptoms almost trebled (6.1% vs 17.7%, p = 0.014) before plateauing at 6 months and returning to baseline at 12 months. Compared to comparisons, RRBSO participants were at 3.0-fold increased risk of chronic depressive symptoms (Wald 95% CI 1.27–7.26), 2.3-fold increased risk of incident depression (95% Wald CI 1.08–5.13) and 2.0-fold increase of incident anxiety (Wald 95% CI 0.78–5.00). Depression and anxiety were slightly more common in Hormone Therapy users after RRBSO vs non-users. ConclusionsRRBSO leads to a rapid increase in clinically significant depressive and anxiety symptoms despite Hormone Therapy use.

Urinary PGE-M Levels and Risk of Ovarian Cancer.

Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

Posttraumatic Stress Disorder Is Associated with Increased Risk of Ovarian Cancer: A Prospective and Retrospective Longitudinal Cohort Study.

Ovarian cancer is the deadliest gynecologic cancer. Chronic stress accelerates tumor growth in animal models of ovarian cancer. We therefore postulated that posttraumatic stress disorder (PTSD) may be associated with increased risk of ovarian cancer. We used data from the Nurses' Health Study II, a longitudinal cohort study with 26 years of follow-up, conducted from 1989 to 2015 with 54,710 subjects. Lifetime PTSD symptoms were measured in 2008. Self-reported ovarian cancer was validated with medical records. Risk of ovarian cancer was estimated with Cox proportional hazards models and further adjusted for known ovarian cancer risk factors (e.g., hormonal factors) and health risk factors (e.g., smoking). Fully prospective secondary analyses examined incident ovarian cancer occurring after PTSD assessment in 2008. In addition, we examined associations by menopausal status. During follow-up, 110 ovarian cancers were identified. Women with high PTSD symptoms had 2-fold greater risk of ovarian cancer versus women with no trauma exposure [age-adjusted HR = 2.10; 95% confidence interval (CI), 1.12-3.95]. Adjustment for health and ovarian cancer risk factors moderately attenuated this association (HR = 1.86; 95% CI, 0.98-3.51). Associations were similar or moderately stronger in fully prospective analyses (age-adjusted HR = 2.38; 95% CI, 0.98-5.76, N cases = 50) and in premenopausal women (HR = 3.42; 95% CI, 1.08-10.85). In conclusion, we show that PTSD symptoms are associated with increased risk of ovarian cancer. Better understanding of the underlying molecular mechanisms could lead to interventions that reduce ovarian cancer risk in women with PTSD and other stress-related mental disorders. SIGNIFICANCE: PTSD is associated with ovarian cancer risk, particularly in premenopausal women. Understanding the underlying molecular mechanisms will aid in formulating ways to reduce ovarian cancer risk associated with chronic stress.

Management of ovarian cancer risk in women with BRCA1/2 pathogenic variants.

KEY POINTS Ovarian cancer has the highest mortality of all female reproductive cancers, largely owing to the absence of early symptoms and lack of effective screening, resulting in diagnosis at an advanced stage. Hereditary breast and ovarian cancers include specifically identified genetic variants

Breastfeeding: Investing in the Future.

Breastfeeding: Investing in the Future.

Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Clinical Practice at a Single Hospital in Korea.

BackgroundThe risk of ovarian malignancy algorithm (ROMA) is used for assessing ovarian cancer risk in women with a pelvic mass. Its diagnostic accuracy is variable. We investigated whether the clinically acceptable minimal sensitivity of >80.0% could be obtained with the suggested cutoff of 7.4%/25.3% for pre/postmenopausal women and with adjusted cutoffs set to a specificity of ≥75.0% or a sensitivity of 95.0%, in a hospital with a lower ovarian cancer (OC) prevalence than previously reported.MethodsROMA scores were calculated from measurements of human epididymis protein 4 and cancer antigen 125 in blood specimens from 443 patients with a pelvic mass. The ROMA-based risk group was compared against biopsy (N=309) or clinical follow-up with imaging (N=134) results. The ROMA sensitivity and specificity for predicting epithelial OC (EOC) and borderline ovarian tumor (BOT) were calculated for the suggested and adjusted cutoff values.ResultsWhen targeting BOT and EOC, the prevalence was 7.4% and sensitivity and specificity at the suggested cutoff were 63.6% and 90.7%, respectively. Sensitivity was 81.8% at the 4.65%/13.71% cutoff set to a specificity of 75.0%. When targeting only EOC, the prevalence was 4.1% and sensitivity and specificity at the suggested cutoff were 77.8% and 89.4%, respectively. Sensitivity was 88.9% at the 4.78%/14.35% cutoff set to a specificity of 75.0%.ConclusionsThe sensitivity of ROMA was lower than expected when using the suggested cutoff. When using the adjusted cutoff, its sensitivity reached 80.0%.

Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study

ObjectivesTo investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.DesignProspective, nationwide cohort study.SettingDenmark,...

New knowledge and insights about the malignant transformation of endometriosis.

Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas. Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long-term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis-associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis.

Long and irregular menstrual cycles, polycystic ovary syndrome, and ovarian cancer risk in a population-based case-control study.

Long and irregular menstrual cycles, a hallmark of polycystic ovary syndrome (PCOS), have been associated with higher androgen and lower sex hormone binding globulin levels and this altered hormonal environment may increase the risk of specific histologic subtypes of ovarian cancer. We investigated whether menstrual cycle characteristics and self-reported PCOS were associated with ovarian cancer risk among 2,041 women with epithelial ovarian cancer and 2,100 controls in the New England Case-Control Study (1992-2008). Menstrual cycle irregularity, menstrual cycle length, and PCOS were collected through in-person interview. Unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for ovarian cancer risk overall, and polytomous logistic regression to evaluate whether risk differed between histologic subtypes. Overall, we observed no elevation in ovarian cancer risk for women who reported periods that were never regular or for those reporting a menstrual cycle length of >35 days with ORs of 0.87 (95% CI = 0.69-1.10) and 0.83 (95% CI = 0.44-1.54), respectively. We observed no overall association between self-reported PCOS and ovarian cancer (OR = 0.97; 95% CI = 0.61-1.56). However, we observed significant differences in the association with menstrual cycle irregularity and risk of ovarian cancer subtypes (pheterogeneity = 0.03) as well as by BMI and OC use (pinteraction < 0.01). Most notable, menstrual cycle irregularity was associated with a decreased risk of high grade serous tumors but an increased risk of serous borderline tumors among women who had never used OCs and those who were overweight. Future research in a large collaborative consortium may help clarify these associations.

Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk

Background/Aims: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. Methods: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. Results: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta-analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). Conclusion: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future.