Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.

INTRODUCTION: Cancer health disparities are widespread. Nevertheless, the disparities in outcomes among diverse survivors of cancer ages 65 years and older ("older") have not been systematically evaluated. METHODS: We conducted a scoping review of original research articles published between January 2016 and September 2023 and indexed in Medline (Ovid), Embase, Scopus, and CINAHL databases. We included studies evaluating racial, ethnic, socioeconomic disadvantaged, geographic, sexual and gender, and/or persons with disabilities disparities in treatment, survivorship, and mortality among older survivors of cancer. We excluded studies with no a priori aims related to a health disparity, review articles, conference proceedings, meeting abstracts, studies with unclear methodologies, and articles in which the disparity group was examined only as an analytic covariate. Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. RESULTS: After searching and removing duplicates, 2573 unique citations remained and after screening 59 articles met the inclusion criteria. Many investigated more than one health disparity, and most focused on racial and ethnic (n = 44) or socioeconomic (n = 25) disparities; only 10 studies described geographic disparities, and none evaluated disparities in persons with disabilities or due to sexual and gender identity. Research investigating disparities in outcomes among diverse older survivors of cancer is increasing gradually-68% of eligible articles were published between 2020 and 2023. Most studies focused on the treatment phase of care (n = 28) and mortality (n = 26), with 16 examined disparities in survivorship, symptoms, or quality of life. Most research was descriptive and lacked analyses of potential underlying mechanisms contributing to the reported disparities. CONCLUSION: Little research has evaluated the effect of strategies to reduce health disparities among older patients with cancer. This lack of evidence perpetuates cancer inequities and leaves the cancer care system ill equipped to address the unique needs of the rapidly growing and increasingly diverse older adult cancer population.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes. OBJECTIVE: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. METHODS: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. RESULTS: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (ß = 0.03; 95 % CrI = 0.20, 0.25), 50th (ß = 0.02; 95 % CrI = -0.16, 0.19), and 90th (ß = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture. CONCLUSION: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

PURPOSE: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. METHODS: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. RESULTS: Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms. CONCLUSIONS: Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium.

BACKGROUND: Most studies examining post-menopausal menopausal hormone therapy (MHT) use and ovarian cancer risk have focused on White women and few have included Black women. METHODS: We evaluated MHT use and ovarian cancer risk in Black (n = 800 cases, 1783 controls) and White women (n = 2710 cases, 8556 controls), using data from the Ovarian Cancer in Women of African Ancestry consortium. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MHT use with ovarian cancer risk, examining histotype, MHT type and duration of use. RESULTS: Long-term MHT use, ≥10 years, was associated with an increased ovarian cancer risk for White women (OR = 1.38, 95%CI: 1.22-1.57) and the association was consistent for Black women (OR = 1.20, 95%CI: 0.81-1.78, pinteraction = 0.4). For White women, the associations between long-term unopposed estrogen or estrogen plus progesterone use and ovarian cancer risk were similar; the increased risk associated with long-term MHT use was confined to high-grade serous and endometroid tumors. Based on smaller numbers for Black women, the increased ovarian cancer risk associated with long-term MHT use was apparent for unopposed estrogen use and was predominately confined to other epithelial histotypes. CONCLUSION: The association between long-term MHT use and ovarian cancer risk was consistent for Black and White women.

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

BACKGROUND: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. METHODS: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. RESULTS: Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. CONCLUSION: Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Racial Differences in the Association of Endometriosis and Uterine Leiomyomas With the Risk of Ovarian Cancer.

OBJECTIVE: To evaluate associations between endometriosis and uterine leiomyomas with ovarian cancer risk by race and the effect of hysterectomy on these associations. METHODS: We used data from four case-control studies and two case-control studies nested within prospective cohorts in the OCWAA (Ovarian Cancer in Women of African Ancestry) consortium. The study population included 3,124 Black participants and 5,458 White participants, of whom 1,008 Black participants and 2,237 White participants had ovarian cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs for the associations of endometriosis and leiomyomas with ovarian cancer risk, by race, stratified by histotype and hysterectomy. RESULTS: The prevalences of endometriosis and leiomyomas were 6.4% and 43.2% among Black participants and 7.0% and 21.5% among White participants, respectively. Endometriosis was associated with an increased risk of endometrioid and clear-cell ovarian cancer in both racial groups (eg, OR for endometrioid tumors for Black and White participants 7.06 [95% CI 3.86-12.91] and 2.17 [95% CI 1.36-3.45], respectively, Phetereogeneity =.003). The association between endometriosis and ovarian cancer risk in White participants was stronger in those without hysterectomy, but no difference was observed in Black participants (all Pinteraction ≥.05). Leiomyomas were associated with an elevated risk of ovarian cancer only in those without hysterectomy in both Black (OR 1.34, 95% CI 1.11-1.62) and White (OR 1.22, 95% CI 1.05-1.41) participants (all Pinteraction ≥.05). CONCLUSIONS: Black and White participants with endometriosis had a higher risk of ovarian cancer, and hysterectomy modified this association among White participants. Leiomyomas were associated with an increased risk of ovarian cancer in both racial groups, with hysterectomy modifying the risk in both groups. Understanding how racial differences in access to care and treatment options (eg, hysterectomy) may help guide future risk reduction strategies.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

BACKGROUND: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. METHODS: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. RESULTS: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. CONCLUSIONS: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

Association between major discrimination and deficit accumulation in African American cancer survivors: The Detroit Research on Cancer Survivors Study.

BACKGROUND: Discrimination can adversely affect health and accelerate aging, but little is known about these relationships in cancer survivors. This study examines associations of discrimination and aging among self-identified African American survivors. METHODS: A population-based sample of 2232 survivors 20-79 years old at diagnosis were enrolled within 5 years of breast (n = 787), colorectal (n = 227), lung (n = 223), or prostate (n = 995) cancer between 2017 and 2022. Surveys were completed post-active therapy. A deficit accumulation index measured aging-related disease and function (score range, 0-1, where <0.20 is robust, 0.20 to <0.35 is pre-frail, and 0.35+ is frail; 0.06 is a large clinically meaningful difference). The discrimination scale assessed ever experiencing major discrimination and seven types of events (score, 0-7). Linear regression tested the association of discrimination and deficit accumulation, controlling for age, time from diagnosis, cancer type, stage and therapy, and sociodemographic variables. RESULTS: Survivors were an average of 62 years old (SD, 9.6), 63.2% reported ever experiencing major discrimination, with an average of 2.4 (SD, 1.7) types of discrimination events. Only 24.4% had deficit accumulation scores considered robust (mean score, 0.30 [SD, 0.13]). Among those who reported ever experiencing major discrimination, survivors with four to seven types of discrimination events (vs. 0-1) had a large, clinically meaningful increase in adjusted deficits (0.062, p < .001) and this pattern was consistent across cancer types. CONCLUSION: African American cancer survivors have high deficit accumulated index scores, and experiences of major discrimination were positively associated with these deficits. Future studies are needed to understand the intersectionality between aging, discrimination, and cancer survivorship among diverse populations.

Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.

PURPOSE: To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls. METHODS: English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results. RESULTS: There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls (P interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance (v controls), with significant interactions with CRP only for the Trails B test. CONCLUSION: Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.

Associations between quantitative measures of TDLU involution and breast tumor molecular subtypes among breast cancer cases in the Black Women's Health Study: a case-case analysis.

BACKGROUND: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women's Health Study (BWHS). METHODS: We assessed quantitative TDLU metrics (TDLU count/100mm2, TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size. RESULTS: Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively. CONCLUSION: Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype.

Racial differences in the association of body mass index and ovarian cancer risk in the OCWAA Consortium.

BACKGROUND: Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race. METHODS: We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models. RESULTS: The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (ORBMI 30+= 1.62, 95% CI: 1.16, 2.26) and White women with obesity (ORBMI 30+= 1.20, 95% CI: 1.02, 2.42) compared to non-obese. Obesity was associated with higher NHGS risk in White women who never used HT (ORBMI 30+= 1.40, 95% CI: 1.08, 1.82). Higher NHGS ovarian cancer risk was observed for AA women who ever used HT (ORBMI 30+= 2.66, 95% CI: 1.15, 6.13), while in White women, there was an inverse association between recent BMI and risk of EOC and HGS in ever-HT users (EOC ORBMI 30+= 0.81, 95% CI: 0.69, 0.95, HGS ORBMI 30+= 0.73, 95% CI: 0.61, 0.88). CONCLUSION: Obesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype.

Correlates of whole blood metal concentrations among reproductive-aged Black women.

BACKGROUND: Metals may influence reproductive health, but few studies have investigated correlates of metal body burden among reproductive-aged women outside of pregnancy. Furthermore, while there is evidence of racial disparities in exposure to metals among U.S. women, there is limited research about correlates of metal body burden among Black women. OBJECTIVE: To identify correlates of whole blood metal concentrations among reproductive-aged Black women. METHODS: We analyzed cross-sectional data from a cohort of 1664 Black women aged 23-35 years in Detroit, Michigan, 2010-2012. We collected blood samples and questionnaire data. We measured concentrations of 17 metals in whole blood using inductively-coupled plasma-mass spectrometer-triple quadrupole and total mercury using Direct Mercury Analyzer-80. We used multivariable linear regression models to identify sociodemographic, environmental, reproductive, and dietary correlates of individual metal concentrations. RESULTS: In adjusted models, age was positively associated with multiple metals, including arsenic, cadmium, and mercury. Education and income were inversely associated with cadmium and lead. Current smoking was strongly, positively associated with cadmium and lead. Alcohol intake in the past year was positively associated with arsenic, barium, copper, lead, mercury, vanadium, and zinc. Having pumped gasoline in the past 24 h was positively associated with cadmium, chromium, and molybdenum. Having lived in an urban area for the majority of residence in Michigan was positively associated with arsenic, lead, and nickel. Higher water intake in the past year was positively associated with several metals, including lead. Fish intake in the past year was positively associated with arsenic, cesium, and mercury. We also observed associations with body mass index, season, and other environmental, reproductive, and dietary factors. SIGNIFICANCE: We identified potential sources of exposure to metals among reproductive-aged Black women. Our findings improve understanding of exposures to metals among non-pregnant reproductive-aged women, and can inform policies in support of reducing disparities in exposures. IMPACT STATEMENT: There are racial disparities in exposures to metals. We analyzed correlates of blood metal concentrations among reproductive-aged Black women in the Detroit, Michigan metropolitan area. We identified sociodemographic, anthropometric, lifestyle, environmental, reproductive, and dietary correlates of metal body burden. Age was positively associated with several metals. Education and income were inversely associated with cadmium and lead, indicating socioeconomic disparities. We identified potential exposure sources of metals among reproductive-aged Black women, including smoking, environmental tobacco smoke, pumping gasoline, living in an urban area, and intake of alcohol, water, fish, and rice.

Associating persistent self-reported cognitive decline with neurocognitive decline in older breast cancer survivors using machine learning: The Thinking and Living with Cancer study.

INTRODUCTION: Many cancer survivors report cognitive problems following diagnosis and treatment. However, the clinical significance of patient-reported cognitive symptoms early in survivorship can be unclear. We used a machine learning approach to determine the association of persistent self-reported cognitive symptoms two years after diagnosis and neurocognitive test performance in a prospective cohort of older breast cancer survivors. MATERIALS AND METHODS: We enrolled breast cancer survivors with non-metastatic disease (n = 435) and age- and education-matched non-cancer controls (n = 441) between August 2010 and December 2017 and followed until January 2020; we excluded women with neurological disease and all women passed a cognitive screen at enrollment. Women completed the FACT-Cog Perceived Cognitive Impairment (PCI) scale and neurocognitive tests of attention, processing speed, executive function, learning, memory and visuospatial ability, and timed activities of daily living assessments at enrollment (pre-systemic treatment) and annually to 24 months, for a total of 59 individual neurocognitive measures. We defined persistent self-reported cognitive decline as clinically meaningful decline (3.7+ points) on the PCI scale from enrollment to twelve months with persistence to 24 months. Analysis used four machine learning models based on data for change scores (baseline to twelve months) on the 59 neurocognitive measures and measures of depression, anxiety, and fatigue to determine a set of variables that distinguished the 24-month persistent cognitive decline group from non-cancer controls or from survivors without decline. RESULTS: The sample of survivors and controls ranged in age from were ages 60-89. Thirty-three percent of survivors had self-reported cognitive decline at twelve months and two-thirds continued to have persistent decline to 24 months (n = 60). Least Absolute Shrinkage and Selection Operator (LASSO) models distinguished survivors with persistent self-reported declines from controls (AUC = 0.736) and survivors without decline (n = 147; AUC = 0.744). The variables that separated groups were predominantly neurocognitive test performance change scores, including declines in list learning, verbal fluency, and attention measures. DISCUSSION: Machine learning may be useful to further our understanding of cancer-related cognitive decline. Our results suggest that persistent self-reported cognitive problems among older women with breast cancer are associated with a constellation of mild neurocognitive changes warranting clinical attention.

Race Differences in the Associations between Menstrual Cycle Characteristics and Epithelial Ovarian Cancer.

BACKGROUND: Menstrual cycle characteristics-including age at menarche and cycle length- have been associated with ovarian cancer risk in White women. However, the associations between menstrual cycle characteristics and ovarian cancer risk among Black women have been sparsely studied. METHODS: Using the Ovarian Cancer in Women of African Ancestry (OCWAA) Consortium that includes 1,024 Black and 2,910 White women diagnosed with epithelial ovarian cancer (EOC) and 2,325 Black and 7,549 White matched controls, we investigated associations between menstrual cycle characteristics (age at menarche, age at menstrual regularity, cycle length, and ever missing three periods) and EOC risk by race and menopausal status. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Black women were more likely to be <11 years at menarche than White women (controls: 9.9% vs. 6.0%). Compared with ≥15 years at menarche, <11 years was associated with increased EOC risk for White (OR = 1.25; 95% CI, 0.99-1.57) but not Black women (OR = 1.10; 95% CI, 0.80-1.55). Among White women only, the association was greater for premenopausal (OR = 2.20; 95% CI, 1.31-3.68) than postmenopausal women (OR = 1.06; 95% CI, 0.82-1.38). Irregular cycle length was inversely associated with risk for White (OR = 0.78; 95% CI, 0.62-0.99) but not Black women (OR = 1.06; 95% CI, 0.68-1.66). CONCLUSIONS: Earlier age at menarche and cycle irregularity are associated with increased EOC risk for White but not Black women. IMPACT: Associations between menstrual cycle characteristics and EOC risk were not uniform by race.

Racial disparities in epithelial ovarian cancer survival: An examination of contributing factors in the Ovarian Cancer in Women of African Ancestry consortium.

Black women diagnosed with epithelial ovarian cancer have poorer survival compared to white women. Factors that contribute to this disparity, aside from socioeconomic status and guideline-adherent treatment, have not yet been clearly identified. We examined data from the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium which harmonized data on 1074 Black women and 3263 white women with ovarian cancer from seven US studies. We selected potential mediators and confounders by examining associations between each variable with race and survival. We then conducted a sequential mediation analysis using an imputation method to estimate total, direct, and indirect effects of race on ovarian cancer survival. Black women had worse survival than white women (HR = 1.30; 95% CI 1.16-1.47) during study follow-up; 67.9% of Black women and 69.8% of white women died. In our final model, mediators of this disparity include college education, nulliparity, smoking status, body mass index, diabetes, diabetes/race interaction, postmenopausal hormone (PMH) therapy duration, PMH duration/race interaction, PMH duration/age interaction, histotype, and stage. These mediators explained 48.8% (SE = 12.1%) of the overall disparity; histotype/stage and PMH duration accounted for the largest fraction. In summary, nearly half of the disparity in ovarian cancer survival between Black and white women in the OCWAA consortium is explained by education, lifestyle factors, diabetes, PMH use, and tumor characteristics. Our findings suggest that several potentially modifiable factors play a role. Further research to uncover additional mediators, incorporate data on social determinants of health, and identify potential avenues of intervention to reduce this disparity is urgently needed.