Abstract Background: The 2014 and 2020 World Health Organization (WHO) diagnostic classification guidelines for epithelial ovarian cancer (EOC) standardized histotype classification, improved reproducibility across pathologists, and revealed distinct survival differences by histotype. EOC histotype distributions have not been characterized by racial/ethnic groups on a population level using these updated guidelines. We performed centralized pathology review using the WHO 2020 guidelines to characterize distributions of EOC histotypes across Black, Hispanic, non-Hispanic (NH) Asian and Pacific Islander (API), and NH white groups. Methods: The Kaiser Permanente Research on Ovarian Cancer Survival study includes 6,067 EOC cases ages 18 years and older diagnosed in 2000-2022 who received care for their EOC at Kaiser Permanente Northern California. Original diagnostic slides were centrally reviewed using 2020 WHO guidelines for a subset of 2,470 cases (median 8 slides/patient, range 1-80). Slides for 20 cases did not contain tumor, and 109 were determined not to be EOC, leaving 2,341 cases for analysis. We assessed concordance of the distribution of EOC histotypes before (original diagnosis) and after re-review by calculating unweighted Cohen’s Kappa for the cohort overall, and separately for racial/ethnic groups. Results: Overall there was substantial agreement of histotype assignment between the original diagnosis and the pathologist’s review (Kappa = 0.67). Agreement varied across racial/ethnic groups, with substantial agreement for NH API (n=640), Hispanic (n=522), and NH white groups (n=928; Kappas 0.73, 0.67, and 0.61, respectively), but moderate agreement for Black individuals (n=242; Kappa 0.59). Overall, proportions of the histotypes before and after study review increased for high grade serous (HGSC) from 58% to 62%; 14% to 17% for endometrioid; 2% to 3% for low grade serous; decreased for carcinoma, NOS from 5% to 0.6% and for grouped rare EOC histotypes including mixed from 4% to 2%; and were unchanged for clear cell, mucinous, and carcinosarcoma (9%, 4%, and 3%, respectively). The highest proportion of HGSC was among Black individuals (73%), and the lowest among NH API individuals (50%), with similar prevalences for Hispanic and NH white individuals (64% and 66%, respectively). Endometrioid, clear cell, and mucinous histotypes were more common among NH API individuals (23%, 14%, and 6%, respectively) compared with the other groups (ranges of 12-16%, 6-8%, and 2-3%, respectively). Conclusions: Improved histotype assignment using WHO 2020 refined distinct differences in histotype distributions by race/ethnicity. Specifically, Black individuals are more likely to be diagnosed with the aggressive HGSC histotype, whereas among NH API individuals non-HGSC histotypes were more common, specifically clear cell, endometrioid, and mucinous histotypes. Citation Format: Jennifer Anne Doherty, Martin Koebel, Jia Li, Laurie Grieshober, Valerie S. Lee, Lisa Moy, Juraj Kavecansky, Lindsay Jane Collin, Scarlett L. Gomez, Elisa V. Bandera, Lawrence H. Kushi. Epithelial ovarian cancer histotype distributions by race/ethnicity in Kaiser Permanente Northern California, 2000-2022 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3565.

High-grade serous ovarian carcinoma (HGSC) is an aggressive malignancy for which bulk transcriptomic subtypes are used to stratify tumors, interpret biology, and guide biomarker development. The four TCGA-derived subtypes, mesenchymal (C1.MES), immunoreactive (C2.IMM), proliferative (C5.PRO), and differentiated (C4.DIF), are consistently observed across cohorts. However, despite their prominence, these subtypes have not translated into therapeutic utility, and their biological basis remains unresolved. Here, we show that HGSC transcriptomic subtypes are largely determined by tumor cellular composition rather than intrinsic malignant transcriptional programs. By integrating controlled single-cell-derived pseudobulk simulations with deconvolution-based analysis of 1,834 primary HGSC tumors across RNA-seq and microarray cohorts, we demonstrate that subtype probabilities align along a composition-driven axis of stromal and immune variation. Cellular composition alone predicted subtype labels with high accuracy (ROC-AUC = 0.81-0.95) and explained a substantial fraction of subtype-associated transcriptomic variation, with the mesenchymal (C1.MES) subtype representing the most robust and reproducible example of composition-driven signal. Although a secondary, composition-independent expression signal is detectable, it does not define the dominant structure of subtype classification. These findings redefine HGSC transcriptomic subtypes as features of the tumor ecosystem rather than discrete malignant states. This reinterpretation has immediate implications for studies that use subtype labels to infer tumor-intrinsic biology and provides a generalizable framework for separating composition-driven and intrinsic signals in bulk tumor data.

Supplementary Table from Body Mass Index and Mammographic Density in a Multiracial and Multiethnic Population-Based Study

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content.RESULTSPositive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8+ T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype.CONCLUSIONThe tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy.FUNDINGOvarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; Medical Research Council (MRC); National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Abstract Based on previous models, among individuals who are not known to carry a pathogenic variant, lifetime risk of ovarian cancer ranges between ~0.1% and ~11%. Risk stratification to identify the people at the higher end of this lifetime risk range is of paramount importance for prevention efforts. Previous risk stratification models for ovarian cancer were based on a limited number of risk/protective factors. Further, we have also shown that risk estimates differ by menopausal status which most models have not considered. We aimed to develop and internally validate a risk stratification model for ovarian cancer that considers 15 unequivocal risk/protective factors and properly accounts for effect modification by menopausal status. We used data from nine studies (7,984 cases, 12,260 controls) participating in the Ovarian Cancer Association Consortium (OCAC). The data were split into a training set and a test set that comprised 80% and 20% of the OCAC dataset, respectively. Seven risk factors (body mass index, height, later age at menopause, menopausal hormonal therapy use, first-degree family history of ovarian cancer, endometriosis, and a polygenic score of 36 common genetic variants) and eight protective factors (later age at menarche, parity, breastfeeding, incomplete pregnancy, later age at last pregnancy, tubal ligation, combined oral contraceptive use and depot-medroxyprogesterone acetate use) were included. Other risk/protective factors such as talcum powder or aspirin use were not included due to high proportions of missing values. We fit multiplicative logistic regression models separately by menopausal status group in the training set to determine the associations between the factors and ovarian cancer. All models were adjusted for race/ethnicity, education level, age and OCAC study. In the test set, we calculated a summary relative risk for every combination of the 15 risk/protective factors (hereafter called a risk profile) based on the estimates from the training set. The summary relative risk was then translated into an absolute risk: the frequency-weighted average of all the profile-specific relative risks was scaled to the average absolute risk, and then this scaling factor was applied to each profile-specific relative risk and its confidence interval (CI). The range of absolute lifetime risks observed in the test set was 0.1%-7.2% using 15 factors, accounting for menopausal status. The area under the receiving operating curve (AUC) was 0.67 (95% CI 0.65-0.68). This is slightly higher than the previous risk stratification models (AUC=0.55-0.66). External validation of our risk stratification model in a longitudinal cohort is warranted, as our findings suggest that there is a subset of individuals at the higher end of the risk range who would be potential candidates for primary prevention strategies including salpingectomy. Citation Format: Minh Tung Phung, Alice W. Lee, Karen McLean, Lilah Khoja, Hoda Anton-Culver, Elisa V. Bandera, Jennifer Anne Doherty, Renee T. Fortner, Marc T. Goodman, Francesmary Modugno, Paul D. P. Pharoah, Kathryn L. Terry, Penelope M. Webb, Anna H. Wu, Andrew Berchuck, Gillian E. Hanley, Bhramar Mukherjee, Malcolm C. Pike, Celeste Leigh Pearce, Britton Trabert. Development and validation of an improved risk stratification model for ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B047.

Background Type 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data. Methods This was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM. ICD codes and C-peptide levels were used to identify patients for chart review to confirm ICI-induced T1DM. Baseline blood specimens were studied for proteomic and immunophenotypic changes. Results Between 2011 and 2023, 18 of 3744 patients treated at Huntsman Cancer Institute with ICIs were confirmed to have ICI-induced T1DM (0.48%). Eleven of the 18 patients received anti-PD1 monotherapy, 4 received anti-PD1 plus chemotherapy or targeted therapy, and 3 received ipilimumab plus nivolumab. The mean time to onset was 218 days (range 22-418 days). Patients had sudden elevated serum glucose within 2-3 weeks prior to diagnosis. Sixteen (89%) presented with diabetic ketoacidosis. Three of 12 patients had positive T1DM-associated autoantibodies. All patients with T1DM became insulin-dependent through follow-up. At median follow-up of 21.9 months (range 8.4-82.4), no patients in the melanoma group had progressed or died from disease. In the melanoma group, best responses were 2 complete response and 2 partial response while on active treatment; none in the adjuvant group had disease recurrence. Proteomic analysis of baseline blood suggested low inflammatory (IL-6, OSMR) markers and high metabolic (GLO1, DXCR) markers in ICI-induced T1DM cohort. Conclusions Our case series demonstrates rapid onset and irreversibility of ICI-induced T1DM. Melanoma patients with ICI-induced T1DM display excellent clinical response and survival. Limited proteomic data also suggested a unique proteomic profile. Our study helps clinicians to understand the unique clinical presentation and long-term outcomes of this rare irAE for best clinical management.

Supplemental Methods: to be published with the manuscript.

Ovarian cancer is the fifth leading cause of cancer-associated mortality among US women with survival disparities seen across race, ethnicity, and socioeconomic status, even after accounting for histology, stage, treatment, and other clinical factors. Neighborhood context can play an important role in ovarian cancer survival, and, to the extent to which minority racial and ethnic groups and populations of lower socioeconomic status are more likely to be segregated into neighborhoods with lower quality social, built, and physical environment, these contextual factors may be a critical component of ovarian cancer survival disparities. Understanding factors associated with ovarian cancer outcome disparities will allow clinicians to identify patients at risk for worse outcomes and point to measures, such as social support programs or transportation aid, that can help to ameliorate such disparities. However, research on the impact of neighborhood contextual factors in ovarian cancer survival and in disparities in ovarian cancer survival is limited. This commentary focuses on the following neighborhood contextual domains: structural and institutional context, social context, physical context represented by environmental exposures, built environment, rurality, and healthcare access. The research conducted to date is presented and clinical implications and recommendations for future interventions and studies to address disparities in ovarian cancer outcomes are proposed.

Supplemental Table 1: Detailed characteristics of studies included in the ASSET meta-analysis of DNA damage repair and signaling genes. Supplemental Table 2: DNA repair gene, region, and final SNP selection data, using human reference genome assembly, GRCh38. Supplemental Table 3: List of all DNA repair genes and DNA repair pathways included in this study. Supplemental Table 4: Statistical associations (p-values) for cancer risk versus genetic variation within DNA repair pathways. Sensitivity analysis of Table 3, with RAD51B, MSH5, and BRCA2 gene removed from analysis. Statistically significant values are in bold (p < 0.05). Supplemental Table 5: Statistical associations (p-values) for cancer risk versus genetic variation within DNA repair pathways. Sensitivity analysis of Table 3, with 6 genes removed from the analysis -- all genes containing loci with individual SNP associations of p < 1 x 10-4. Statistically significant values are in bold (p < 0.05).

Abstract Background: Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality among women in the US. Racial and ethnic disparities in ovarian cancer outcomes exist, wherein non-Hispanic Black (NHB) women are 40% more likely to die compared with non-Hispanic White (NHW) women. Comorbidity burden is differential by race and ethnicity and has the potential to affect treatment and outcomes. Our objective was to evaluate the association between comorbidities, present at the time of diagnosis, and mortality, and to evaluate if comorbidities contributed to racial and ethnic disparities in mortality. Methods: The KP ROCS (Kaiser Permanente Research on Ovarian Cancer Survival) Study includes women diagnosed with invasive ovarian, fallopian, or peritoneal cancer between 2000 and 2018 at KP Northern California, older than 18 years and residing in California at diagnosis. Comorbidities were identified using ICD-9/10 and procedural codes up to five years preceding the ovarian cancer diagnosis. We computed hazard ratios (HRs) and 95% confidence intervals (CIs) associating individual comorbidities and the Charlson Comorbidity Index (CCI) with all-cause mortality, and the racial disparities (Hispanic, non-Hispanic Asian, and NHB vs. NHW) in all-cause mortality by comorbidity, adjusting for age and stage. Results: Of 4,910 ovarian cancer patients in the KP ROCS cohort, 605 (12%) are Hispanic, 672 (13%) are non-Hispanic Asian, 282 (5.5%) are NHB, and 3,321 (74%) are NHW. At diagnosis, NHB and Hispanic ovarian cancer patients were more likely to present with diabetes than non-Hispanic Asian and NHW women (NHB=16%, Hispanic=13% vs non-Hispanic Asian=10%, NHW=8%). Cardiovascular disease was more common among NHB women compared with other racial and ethnic groups (NHB=37% vs. Hispanic=26%, non-Hispanic Asian=19%, NHW=32%). Moreover, the net burden of comorbidities (CCI=3+) was higher among NHB women compared with other racial and ethnic groups (NHB=22% vs non-Hispanic Asian=9%, Hispanic=13%, NHW=13%). In the multivariable-adjusted models, ovarian cancer patients with diabetes (HR=1.16, 95%CI 1.03, 1.31), cardiovascular disease (HR=1.32, 95% CI 1.22, 1.44), hypertension (HR=1.07, 95%CI 0.99, 1.16), or renal disease (HR=1.25, 95%CI, 1.14, 1.38 at the time of their diagnosis were more likely to die than those without the corresponding comorbidity. NHB ovarian cancer patients had an increased hazard of mortality across nearly all comorbid conditions compared with NHW patients, whereas Hispanic women had equivalent mortality rates as NHW patients, and non-Hispanic Asian patients had reduced mortality rates compared with NHW patients across each individual comorbidity. Conclusions: These analyses indicate that the presence of comorbid conditions negatively impacts survival among ovarian cancer patients. Moreover, NHB ovarian cancer patients are more likely to present with comorbidities at the time of their ovarian cancer diagnosis compared with other racial and ethnic groups, which may partially explain the observed disparities. Citation Format: Lindsay J. Collin, Jia Li, Valerie S. Lee, Juraj Kavecansky, Christine Garcia, Carola Sanchez Diaz, Scarlett Lin Gomez, Jennifer A. Doherty, Elisa V. Bandera, Lawrence H. Kushi. Contribution of comorbid conditions to racial and ethnic disparities in ovarian cancer survival [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B102.

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.

Abstract Introduction Body mass index (BMI) fails to identify up to one‐third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity‐related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk. Methods National Health and Nutrition Examination Survey participants from 1999 to 2018 (N = 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC. Results With metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n = 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer‐free individuals (n = 18,972). Compared with MHNW participants, MUNW participants had a 2.2‐times higher ORC risk [OR (95%CI) = 2.21 (1.27–3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46–4.42), 1.56 (0.91–2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW. Conclusions MUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted.

Pre-diagnosis circulating leukocyte profiles, including higher white blood cell (WBC) counts and neutrophil-to-lymphocyte ratios (NLR), have been reported to be associated with non-small cell lung cancer (NSCLC) risk. Higher neutrophil levels were recently reported to drive NSCLC-WBC count associations, implicating the innate immune response in NSCLC risk and etiology. Though not directly measurable in bio-banked blood, leukocyte subtype proportions can be estimated using established deconvolution algorithms applied to genome-wide DNA methylation data. We previously reported that NSCLC risk was elevated in heavy smokers with greater pre-diagnosis methylation-derived NLR (mdNLR). Here, we examine the influence of each pre-diagnosis mdNLR leukocyte subtype (neutrophils, and lymphocytes: B, Natural Killer, CD8+T, and CD4+T cells), separately on NSCLC risk. In our nested case-control study from the Beta Carotene and Retinol Efficacy Trial of heavy smokers (≥20 pack years), 243 NSCLC cases were 1:1 matched to controls on age (±5 years), sex, race and ethnicity, enrollment (±2 years), smoking status (ever/never), asbestos exposure, and follow-up time. Methylation was assayed on the Illumina EPIC array in whole blood collected on average 4.4 years (range 0.1-10.1) before diagnosis in NSCLC cases. We assessed conditional logistic regression models for each mdNLR-related leukocyte subtype, dichotomized at the median in controls, and further adjusted for continuous age and smoking pack years at blood draw. We evaluated NSCLC risk overall, and in subgroup strata: histotype, sex, smoking status, asbestos exposure, stage at diagnosis, age at blood draw, age at diagnosis, and time between blood draw and diagnosis. A greater than median level of neutrophils was suggestively associated with NSCLC risk (OR=1.40, 95% CI: 0.93-2.12); this association was restricted to squamous cell carcinoma (SCC n=103 pairs; 2.00, 1.03-3.86), with no association for adenocarcinoma (n=132 pairs; 0.99, 0.57-1.73). SCC-neutrophil associations were strongest among former smokers (n=26 pairs; 6.81, 1.48-31.3), cases with ≤ 4.4 years between blood draw and diagnosis (n=48 pairs; 3.00, 1.10-8.14), cases aged > 64.8 years at blood draw (n=56 pairs; 2.66, 1.05-6.73), and cases diagnosed at stage III or IV (n=61 pairs; 2.21, 0.92-5.30). Greater than median lymphocyte levels were suggestively associated with reduced NSCLC (0.71, 0.47-1.08) and SCC risk (0.62, 0.32-1.21), but less so for adenocarcinoma (0.85, 0.48-1.50). Though statistically imprecise, SCC-lymphocyte associations were strongest for CD4+T cells (0.56, 0.28-1.12). Our results indicate that greater pre-diagnosis neutrophil levels may be a biomarker for SCC, but not adenocarcinoma, in heavy smokers. Given the descriptive nature of this analysis, small sample size, and multiple testing, additional research is needed to replicate these findings. Citation Format: Laurie Grieshober, Stefan Graw, Matt J. Barnett, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty. Pre-diagnostic methylation-based leukocyte profiles and non-small cell lung cancer risk in heavy smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3005.

Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.

Abstract Background: Mammographic density (MD) is strongly associated with breast cancer risk. We examined whether body mass index (BMI) partially explains racial and ethnic variation in MD. Methods: We used multivariable Poisson regression to estimate associations between BMI and binary MD [Breast Imaging Reporting and Database System (BI-RADS) A&B versus BI-RADS C&D] among 160,804 women in the Utah mammography cohort. We estimated associations overall and within racial and ethnic subgroups and calculated population attributable risk percents (PAR%). Results: We observed the lowest BMI and highest MD among Asian women, the highest BMI among Native Hawaiian and Pacific Islander women, and the lowest MD among American Indian and Alaska Native (AIAN) and Black women. BMI was inversely associated with MD [RRBMI≥30 vs. BMI<25 = 0.43; 95% confidence interval (CI), 0.42–0.44] in the full cohort, and estimates in all racial and ethnic subgroups were consistent with this strong inverse association. For women less than 45 years of age, although there was statistical evidence of heterogeneity in associations between BMI and MD by race and ethnicity (P = 0.009), magnitudes of association were similar across groups. PAR%s for BMI and MD among women less than 45 years were considerably higher in White women (PAR% = 29.2, 95% CI = 28.4–29.9) compared with all other groups with estimates ranging from PAR%Asain = 17.2%; 95% CI, 8.5 to 25.8 to PAR%Hispanic = 21.5%; 95% CI, 19.4 to 23.6. For women ≥55 years, PAR%s for BMI and MD were highest among AIAN women (PAR% = 37.5; 95% CI, 28.1–46.9). Conclusions: While we observed substantial differences in the distributions of BMI and MD by race and ethnicity, associations between BMI and MD were generally similar across groups. Impact: Distributions of BMI and MD may be important contributors to breast cancer disparities.

PURPOSE:National Cancer Institute (NCI)-Designated Cancer Centers are required to assess and address the needs of their catchments. In rural regions, catchment areas are vast, populations small, and infrastructure for data capture limited, making analyses of cancer patterns challenging.METHODS:The four NCI-Designated Comprehensive Cancer Centers in the southern Rocky Mountain region formed the Four Corners Collaboration (4C2) to address these challenges. Colorectal cancer (CRC) was identified as a disease site where disparities exist. The 4C2 leaders examined how geographic and sociodemographic characteristics were correlated to stage at diagnosis and survival in the region and compared those relationships to a sample from the surveillance, epidemiology, and end results (SEER) program.RESULTS:In 4C2, Hispanics were more likely to live in socioeconomically disadvantaged areas relative to their counterparts in the SEER program. These residency patterns were positively correlated with later stage diagnosis and higher mortality. Living in an area with high-income inequality was positively associated with mortality for Non-Hispanic whites in 4C2. In SEER, Hispanics had a slightly higher likelihood of distant stage disease, and disadvantaged socioeconomic status was associated with poor survival.CONCLUSION:CRC interventions in 4C2 will target socioeconomically disadvantaged areas, especially those with higher income inequality, to improve outcomes among Hispanics and Non-Hispanic whites. The collaboration demonstrates how bringing NCI-Designated Cancer Centers together to identify and address common population catchment issues provides opportunity for pooled analyses of small, but important populations, and thus, capitalize on synergies among researchers to reduce cancer disparities.

Objective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.Setting: Population-based.Patient(s): We included 8,500 women with ovarian cancer, 13,592 control women.Intervention(s): Ten well-established ovarian cancer risk factors.Main Outcome Measure(s): Risk of ovarian cancer for women with and without endometriosis.Result(s): Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-<30 kg/m2 was associated with increased ovarian cancer risk among women with endometriosis (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.00-1.60), but not associated with the risk among women without endometriosis (OR = 0.97; 95% CI, 0.91-1.05) when compared with BMI 18.5-<25 kg/m2; an increased risk was observed for a BMI >= 30 kg/m2, although there was little difference comparing women with endometriosis (OR = 1.21; 95% CI, 0.94- 1.57) to women without (OR = 1.13; 95% CI, 1.04-1.22) (P-interaction = .51). Genital talcum powder use and long-term menopausal estrogen-only therapy use showed increased ovarian cancer risk, but risk appeared greater for those with endometriosis vs. those without (genital talcum powder: OR = 1.38; 95% CI, 1.04-1.84 vs. OR = 1.12; 95% CI, 1.01-1.25, respectively; >= 10 years of estrogen-only therapy: OR = 1.88; 95% CI, 1.09-3.24 vs. OR = 1.42; 95% CI, 1.14-1.76, respectively); neither of these interactions were statistically significant (P-interaction = .65 and P-interaction = .96, respectively).Conclusion(s): The associations between ovarian cancer and most risk factors were similar among women with and without endome-triosis. However, there was some suggestion of differences by endometriosis status for BMI, menopausal hormone therapy use, and gen-ital talcum powder use, highlighting the complexity of ovarian cancer etiology. (Fertil Sterile 2022;118:960-9. (c) 2022 by American Society for Reproductive Medicine.)El resumen esta disponible en Espanol al final del articulo.

Background: The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns sim-ilar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone.Methods: The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchro-nous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endo-metrioid cancers, and stage IA cancers.Results: Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers.Conclusions: We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy.Impact: The possible misdiagnosis associated with clinicopath-ologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level.