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The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS.Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53).The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Objective To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. Methods We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). Results Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). Conclusions The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend

Objectives: Disparities among Black women with cervical cancer in the United States are well known; however, the etiology is not fully understood. Access to oncologic care and adequate insurance coverage likely affect these racial disparities. The aim of this study was to describe factors affecting the ability to receive oncologic care in cervical cancer as a function of race among different regions in the U.S. Methods: A retrospective cohort study was performed using the National Cancer Database (NCDB) among women with stage I-IVA cervical cancer from 2004-2014. To identify factors associated with the receipt of optimal treatment, multivariate logistic regression was used, including an interaction term to determine the relationship of race and region. To evaluate overall survival, a Cox multivariate proportional hazards model was performed, including a similar interaction term. Publicly available data from the NCI, the Society of Gynecologic Oncology, and the United States Census were utilized to compile data regarding availability of cancer centers, gynecologic oncologists, and insurance status by region. Results: A total of 55,659 women with cervical cancer were identified, of whom 9,153 were Black (16.4%). Fewer Black women presented with stage I disease (37.8% versus 47.8%, p Download : Download high-res image (149KB) Download : Download full-size image Conclusions: Black women living in the South of the United States are at particular risk of both inadequate treatment and worse overall survival for cervical cancer after controlling for confounding factors. Population-level data suggests that women in the South may be underinsured and lack access to cancer centers and gynecologic oncologists.

Objective We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status. Methods Tissue microarrays were used to assess ERα and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n=954) on diagnosis date and birth year. NECC controls (n=725) were frequency matched on age. Cases were considered receptor positive if ≥1% of tumor cells stained positive. Associations by ERα and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test. Results 45% of ovarian tumors were PR(+), 78% were ERα(+) and 45% were ERα(+)/PR(+), while 22% were ERα(–)/PR(–). Postmenopausal status was associated with an increased risk of PR(–) tumors (OR: 2.07; 95%CI: 1.15–3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR(–) tumors (OR, per 5years: 0.77; 95%CI: 0.61–0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). Number of children and tubal ligation were more strongly associated with ERα(–) versus ERα(+) tumors (p-het=0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use. Conclusions Postmenopausal women have an increased risk of developing PR(–) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ERα and PR pathways may differ.

Introduction Despite strides in identifying factors that predict risk of ovarian cancer and improvements in ovarian cancer treatment, little is known about factors that predict ovarian cancer survival. Methods We reviewed the literature for analyses of factors before, at, or after diagnosis that may predict survival outcomes, including demographics (e.g., age and race), genetics (e.g., inherited BRCA mutations), hormonal factors (e.g., parity and hormone use), and lifestyle (e.g., physical activity and diet). Results While treatment factors, tumor characteristics and genetic syndromes are predictive of survival, few studies of most hormonal and lifestyle factors have been published; most have evaluated pre-diagnosis factors. For example, we identified eight studies that examined menopausal hormone use prior to diagnosis, reporting a non-significant survival benefit for users compared to non-users, while four studies reported better survival with use after surgery, though only two were significant. Similarly, while increased body size has been extensively studied as potentially associated with reduced survival, other modifiable factors, such as diet and physical activity remain understudied. We identified three studies of pre-diagnosis physical activity and five studies of pre-diagnosis diet, with a suggestive benefit of higher vegetable intake and vigorous physical activity. By contrast, large studies of the impact of race/ethnicity and socioeconomic status (SES) confirm that non-white women and women of lower SES fare more poorly than white women and women of higher SES, respectively. Conclusions Our review of the published literature on predictors of ovarian cancer survival revealed that modifiable lifestyle factors may be related to survival, but that hormonal factors do not strongly predict outcomes in ovarian cancer patients. However, more attention should be paid to women's post-diagnosis survival experience. The dearth of literature on post-diagnosis factors that may improve outcomes makes it difficult to make specific recommendations for survivors.

To describe the clinical characteristics of patients with endosalpingiosis (ES) and examine its association with endometriosis and gynecologic malignancies.We queried the medical record for patients who underwent gynecologic surgery (Gynecologic Surgery Cohort (GSC), n=58,161) from 1998 to 2013 at a single institution for the presence of "endosalpingiosis" (ES). Demographic and clinical characteristics were collected for patients with pathologically confirmed ES (n=838). Within GSC, we compared the frequency of endometriosis and gynecologic malignancies with and without ES. We estimated the expected distribution of ovarian cancer subtypes using cases from the New England Case Control Study (NECC). We used chi-square tests to test for significant differences in frequency distributions and unconditional logistic regression to calculate multivariate odds ratios for the association between ES and ovarian cancer subtypes.We observed concurrent endometriosis (p0.0001), uterine cancer (p0.0001), and ovarian cancer (p0.0001) more frequently in women with ES. Women from the GSC with ES and ovarian cancer were more likely to have serous borderline (OR=10.2, 95% CI=5.1-20.7), clear cell (OR=3.0, 95% CI=1.1-8.0), and invasive mucinous tumors (OR=5.0, 95% CI=1.5-16.6) as compared to ovarian cancer cases from the NECC without ES, after accounting for age, race, menopausal status, parity, tubal ligation, and endometriosis.Women with ES are more likely to also be diagnosed with endometriosis, uterine, and ovarian cancers. Further study is needed to understand these associations so we may appropriately counsel patients with ES diagnosed at time of gynecologic surgery.

CA125 at presentation of ovarian cancer carries important prognostic significance; but, other than tumor characteristics, little is known about factors that influence CA125 levels. We examined the effect of epidemiologic variables and tumor features on CA125 at diagnosis and their effects on survival.CA125 levels before treatment, tumor features, and questionnaire data from 805 women with ovarian cancer receiving care at Partners Hospitals were recorded. CA125 values were log-normalized and generalized linear, logistic, or Cox proportional hazards models used to identify predictors of CA125 and influence on survival in the subset of women with invasive, nonmucinous tumors.The importance of histology, grade, stage, laterality, and presence of ascites on CA125 level was confirmed. For nonmucinous invasive cancers, Jewish ethnicity, parity, prior breast cancer, and family history of breast or ovarian cancer predicted higher CA125, and greater body mass index (BMI), recurrent yeast infections, colitis, and appendectomy predicted lower CA125. A quadratic model best described the relationship between CA125 and age with lower levels in youngest and oldest women. In multivariate modeling, stage, ascites, and prior breast cancer were the strongest predictors of high CA125 and appendectomy and yeast infections strongest predictors of low CA125. A model with these variables plus CA125 revealed high CA125 remains a predictor of poorer survival.Ovarian tumor features and presence of ascites are key determinants of CA125 at diagnosis, but epidemiologic features such as BMI, parity, prior breast cancer, and history of inflammatory conditions of the genitourinary or gastrointestinal tracts may also play a role.

Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene.We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY).Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies.MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings.

Objective Together, steroidogenic acute regulator (StAR) and the cholesterol side chain cleavage enzyme (P450scc), which is encoded by CYP11A1 , mediate the initial and rate-limiting step in steroidogenesis. Given the role of estrogens in endometrial carcinogenesis, we hypothesized that genetic variation in StAR and CYP11A1 genes may influence endometrial cancer risk. Methods We genotyped four CYP11A1 tagging single nucleotide polymorphisms (SNPs) and two StAR SNPs in endometrial cancer case–control studies nested within the Nurses' Health Study (553 cases and 1339 controls) and the Women's Health Study (137 cases and 411 controls). We calculated odds ratios and 95% confidence intervals using conditional and unconditional logistic regression adjusted for endometrial cancer risk factors to examine the association between SNPs/haplotypes and endometrial cancer. Results We observed an increased risk for women carrying the variant allele for rs4555110 (odds ratio (OR)=1.3, 95% confidence interval (CI)=1.1–1.7), rs3825944 (OR=1.4, 95% CI=1.1–1.8), and rs7173655 (OR=1.3, 95% CI=1.0–1.7) CYP11A1 SNPs but no significant associations with CYP11A1 haplotypes. CYP11A1 SNPs were not predictive of plasma estradiol levels. We observed no associations between StAR SNPs and endometrial cancer risk. Conclusions Genetic variants in CYP11A1 may influence endometrial cancer risk or may be markers for causal variants elsewhere. Polymorphisms in StAR are not associated with endometrial cancer risk, but further research is needed.