Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES).

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

Recreational physical activity and survival in African-American women with ovarian cancer.

PURPOSE: While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women. METHODS: We analyzed data from 264 EOC survivors enrolled in a population-based, case-control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1 year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models. RESULTS: RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were < 1.0 but not statistically significant after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for > 0-9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for > 9 MET-hours/week. CONCLUSIONS: Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.

Dietary inflammatory index and risk of epithelial ovarian cancer in African American women.

Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one's diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study, the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR = 1.10, 95% CI = 1.03-1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1 = 1.72; 95% CI = 1.18-2.51). We also observed effect modification by age (p < 0.05), where a strong, significant association between the E-DII and EOC risk was observed among women older than 60 years, but no association was observed in women aged 60 years or younger. Our findings suggest that a more pro-inflammatory diet was associated with an increased EOC risk, especially among women older than 60 years.

Premenopausal Hysterectomy and Risk of Ovarian Cancer in African-American Women.

Although the inverse association between hysterectomy and epithelial ovarian cancer (EOC) was considered well established, investigators in recent studies including women diagnosed after 2000 have observed modest increases in risk. Most studies have been conducted in white women with little representation of African-American women. We examined the relationship between premenopausal hysterectomy and EOC in African-American women and explored whether hormone therapy (HT) modified this association in 614 cases and 743 controls enrolled in the African American Cancer Epidemiology Study (2010-2015). Premenopausal hysterectomy was inversely associated with the odds of EOC (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.56, 1.01). Qualitative interaction by estrogen-only HT was present; among never users of estrogen-only HT, premenopausal hysterectomy was associated with a significantly decreased odds of EOC (OR = 0.65, 95% CI: 0.46, 0.92), whereas among users of estrogen-only HT, a positive association was observed (OR = 1.71, 95% CI: 0.76, 3.84). In a population of African-American women diagnosed after 2000, our overall results are consistent with the inverse association observed in the era before 2000, yet the effect modification by HT suggests that HT use among women who have had hysterectomies may negate the protective effects of hysterectomy on EOC, creating the appearance of a null or slightly increased risk.

Lifetime number of ovulatory cycles and epithelial ovarian cancer risk in African American women.

PURPOSE: Incessant ovulation has been consistently linked to epithelial ovarian cancer (EOC). Although reproductive characteristics differ substantially by race, the association between incessant ovulation and EOC has been evaluated only in populations of predominantly white women. In the present study, we examined the association between lifetime number of ovulatory cycles (LOCs) and EOC risk among African American (AA) women. METHODS: We used data from 534 cases and 722 controls enrolled in the African American Cancer Epidemiology Study. LOCs were determined using the standard method, with modifications to include episodes of irregular or missed periods. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between LOCs and EOC risk overall and by age, while adjusting for appropriate confounders. RESULTS: The mean number of LOCs was 378.2 ± 105.8 for cases and 346.4 ± 117.3 for controls. Women in the highest tertile of LOCs had 59% higher odds of EOC compared to women in the lowest tertile (OR = 1.59; 95% CI = 1.15-2.20). When examining this relationship by age, the positive association with EOC was stronger among women <50 years of age (OR for highest vs. lowest tertile = 2.61; 95% CI = 1.15-5.94), followed by women aged 50-60 years (OR = 2.27; 95% CI = 1.30-3.94). Yet, no association was present among women aged >60 years (OR = 0.79; 95% CI = 0.45-1.40). CONCLUSIONS: In a population of AA women, we observed a positive association between LOCs and EOC risk, providing further support for the hypothesis that incessant ovulation contributes to the etiology of EOC.

Tubal ligation and ovarian cancer risk in African American women.

PURPOSE: Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. METHODS: Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors. RESULTS: An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68-1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35 years or older (OR 0.64; 95% CI 0.41-0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74-1.29) (p for interaction = 0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14-0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36-2.12) and serous (OR 0.94, 95% CI 0.71-1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58-5.82) was based on a low number of cases. CONCLUSIONS: Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.

Analgesic medication use and risk of epithelial ovarian cancer in African American women.

BACKGROUND: Existing literature examining analgesic medication use and epithelial ovarian cancer (EOC) risk has been inconsistent, with the majority of studies reporting an inverse association. Race-specific effects of this relationship have not been adequately addressed. METHODS: Utilising data from the largest population-based case-control study of EOC in African Americans, the African American Cancer Epidemiology Study, the relationship between analgesic use (aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen) and risk of EOC was estimated by multivariate logistic regression. The association of frequency, duration, and indication of analgesic use on EOC risk was also assessed. RESULTS: Aspirin use, overall, was associated with a 44% lower EOC risk (OR=0.56; 95% CI=0.35-0.92) and a 26% lower EOC risk was observed for non-aspirin NSAID use (OR=0.74; 95% CI=0.52-1.05). The inverse association was strongest for women taking aspirin to prevent cardiovascular disease and women taking non-aspirin NSAIDs for arthritis. Significantly decreased EOC risks were observed for low-dose aspirin use, daily aspirin use, aspirin use for <5 years, and occasional non-aspirin NSAID use for a duration of ⩾5 years. No association was observed for acetaminophen use. CONCLUSIONS: Collectively, these findings support previous evidence that any NSAID use is inversely associated with EOC risk.

The Quality of Peer-Reviewed Publications on Surgery for Early Stage Lung Cancer Within the Veterans Health Administration.

The peer-reviewed literature is often referenced to generalize outcomes for lung cancer surgeries performed within the Veterans Health Administration (VHA) and include assessments following resection of early stage non-small-cell lung cancer (NSCLC). We sought to determine the reliability of these reports that are publicly available. A systematic review was undertaken to identify PubMed indexed articles that report postoperative outcomes following surgical resections for stage I NSCLC within the VHA. Only studies that reported American Joint Committee on Cancer staging were included. Eleven studies spanning 49 years (1966-2015) met the inclusion criteria. Two reported findings from national VHA databases while 9 reported outcomes from single institutions. Reporting of outcomes and prognostic factors varied widely between studies and were frequently omitted. This made it difficult to evaluate prognostic factors that may be associated with a wide range of 30- and 90-day perioperative mortality (0-3.8% and 0-6.4%), 3- and 5-year cause-specific survival (72-92% and 32-84%), and 3- and 5- year overall survival (47-85.7% and 24-74%). The quality of peer-reviewed literature that reports outcomes following thoracic surgery for stage I NSCLC in the VHA is inconsistent and precludes accurate assessments for generalizations about the quality of care in this healthcare system. Efforts to develop a dedicated outcome tracking and registry system can provide more meaningful evidence to identify areas for improvement for this often-curable malignancy.

Individual, Social, and Societal Correlates of Health-Related Quality of Life Among African American Survivors of Ovarian Cancer: Results from the African American Cancer Epidemiology Study.

OBJECTIVE: While the incidence of epithelial ovarian cancer (EOC) is lower among African American (AA) women compared with European American (EA) women, AA women have markedly worse outcomes. In this study, we describe individual, social, and societal factors in health-related quality of life (HRQL) in AA women diagnosed with EOC in the African American Cancer Epidemiology Study (AACES) that we hypothesize may influence a patient's capacity to psychosocially adjust to a diagnosis of cancer. METHODS: There were 215 invasive EOC cases included in the analysis. HRQL was measured using the SF-8 component scores for physical (PCS) and mental (MCS) health. We used least squares regression to test the effects of individual dispositional factors (optimism and trait anxiety); social level (perceived social support); and societal-level factors (SES defined as low family income and low educational attainment, and perceived discrimination) on HRQL, while adjusting for patient age, tumor stage, body mass index, and comorbidity. Mediation analysis was applied to test whether social support and physical activity buffer impacts of EOC on HRQL. RESULTS: Optimism, trait anxiety, social support, poverty, and past perceived discrimination were significantly associated with HRQL following diagnosis of EOC. Specifically, higher family income, lower phobic anxiety, and higher social support were associated with better wellbeing on the MCS and PCS (p < 0.01). Higher perceived discrimination was associated with both lower MCS and PCS, whereas higher optimism was associated with higher MCS. Physical activity (MET-min/week) and social support displayed significant overall mediation for effects of SES on MCS and PCS, but not for trait anxiety. CONCLUSIONS: Both pre- and postdiagnosis characteristics of AA women with EOC are important predictors of HRQL after cancer diagnosis. Individual, social, and societal-level factors each contribute to HRQL status with EOC and should be assessed.

Effect of Cultural, Folk, and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women.

BACKGROUND: Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer. METHODS: Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses. RESULTS: Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality. CONCLUSIONS: Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.

Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled analysis of 12 case-control studies.

Background: Ovarian cancer incidence differs substantially by race/ethnicity, but the reasons for this are not well understood. Data were pooled from the African American Cancer Epidemiology Study (AACES) and 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences in epidemiological characteristics with suspected involvement in epithelial ovarian cancer (EOC) aetiology. Methods: We used multivariable logistic regression to estimate associations for 17 reproductive, hormonal and lifestyle characteristics and EOC risk by race/ethnicity among 10 924 women with invasive EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233 Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to evaluate heterogeneity in the risk factor associations by race/ethnicity. Results: We observed statistically significant racial/ethnic heterogeneity for hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02] compared with other racial/ethnic groups. Although not statistically significant, the associations for parity, first-degree family history of ovarian or breast cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had the greatest magnitude of association for parity (≥3 births: OR = 0.38, 95% CI = 0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77, 95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55). Conclusions: Although racial/ethnic heterogeneity was observed for hysterectomy, our findings support the validity of EOC risk factors across all racial/ethnic groups, and further suggest that any racial/ethnic population with a higher prevalence of a modifiable risk factor should be targeted to disseminate information about prevention.

Recreational physical activity and ovarian cancer risk in African American women.

The literature on recreational physical activity (RPA) and ovarian cancer risk is inconclusive and most studies of RPA and ovarian cancer have been conducted in white populations. This study is the first to investigate the association between RPA and ovarian cancer in an exclusively African American (AA) population. We analyzed data from an ongoing U.S. population-based, case-control study of AA women, which included 393 women recently diagnosed with invasive epithelial ovarian cancer (IEOC) and 611 controls. A baseline interview assessed RPA frequency, intensity, and duration. Each RPA intensity was assigned a metabolic equivalent of task (MET) value and MET-min/week were calculated. Unconditional multivariable logistic regression was performed to investigate associations between RPA and IEOC risk. Compared with sedentary women, predominantly mild intensity RPA was significantly inversely associated with IEOC risk for women reporting above median (>297) MET-min/week (odds ratio [OR] = 0.52; 95% confidence interval [CI]: 0.34, 0.78) and nonsignificantly for <297 MET-min/week (OR = 0.71; 95% CI: 0.44, 1.12). Predominantly moderate intensity RPA was associated with significantly increased risk for women reporting above median (>540) MET-min/week (OR = 1.51; 95% CI: 1.03, 2.23). Predominantly strenuous intensity RPA was nonsignificantly associated with lower IEOC risk for women reporting above median (>1800) MET-min/week (OR = 0.72; 95% CI: 0.33, 1.57). The inverse associations for mild and strenuous intensity RPA were most pronounced in obese women (body mass index >30 kg/m(2) ). The findings that mild and strenuous RPA may reduce the risk of IEOC particularly among obese women are difficult to reconcile with the increased risk observed for moderate RPA. Further research is warranted to determine whether these findings are genuine and, if so, their mechanistic basis.

Association between Body Powder Use and Ovarian Cancer: The African American Cancer Epidemiology Study (AACES).

BACKGROUND: Epidemiologic studies indicate increased ovarian cancer risk among women who use genital powder, but this has not been thoroughly investigated in African American (AA) women, a group with a high prevalence of use. We evaluate the relationship between use of genital powder and nongenital powder in invasive epithelial ovarian cancer (EOC). METHODS: Subjects are 584 cases and 745 controls enrolled in the African American Cancer Epidemiology Study (AACES), an ongoing, population-based case-control study of EOC in AA women in 11 geographic locations in the United States. AA controls were frequency matched to cases on residence and age. Logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between genital and nongenital powder exposure and EOC risk, controlling for potential confounders. RESULTS: Powder use was common (62.8% of cases and 52.9% of controls). Genital powder was associated with an increased risk of EOC (OR = 1.44; 95% CI, 1.11-1.86) and a dose-response relationship was found for duration of use and number of lifetime applications (P < 0.05). Nongenital use was also associated with EOC risk, particularly among nonserous EOC cases (OR = 2.28; 95% CI, 1.39-3.74). An association between powder use and upper respiratory conditions suggests an enhanced inflammatory response may explain the association between body powder and EOC. CONCLUSIONS: In a study of AA women, body powder use was significantly associated with EOC risk. IMPACT: The results support that body powder is a modifiable risk factor for EOC among AA women. Cancer Epidemiol Biomarkers Prev; 25(10); 1411-7. ©2016 AACRSee related commentary by Trabert, p. 1369.