A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

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.

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.

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.

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.

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.

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 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.

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.

A population-based psychometric analysis of the insomnia severity index in black women with and without a history of cancer.

Black women are under-represented in insomnia research. Further, cancer treatments increase the risk of late effects, thus affecting the sleep of psychologically and medically vulnerable cancer survivors. The Insomnia Severity Index (ISI) is widely used, but has not been researched in black women, and research in cancer survivors is limited. Prior studies demonstrate that psychometric properties of the ISI are not consistent across samples. This study examined the internal consistency and factor structure of the ISI in 29,500 participants from the Black Women's Health Study, an epidemiological study of black women in the United States. This cohort included 28,214 women without a cancer history and 1,286 cancer survivors. Exploratory, confirmatory and multigroup analyses were conducted to determine the psychometric properties of the ISI in these groups. The mean ISI score was 7.18 (standard deviation [SD] = 6.82). Findings supported the internal consistency reliability of the ISI in black women with (Ω = 0.896) and without (Ω = 0.892) a cancer history. Exploratory factor analyses supported a one-factor structure. Confirmatory factor analyses indicated that fit of this one-factor model was not robust in survivors (Satorra-Bentler chi-square [χSB2 (14)] = 197.78, comparative fit index [CFI] = 0.928, root mean-square error of approximation [RMSEA] = 0.143) or in women with no cancer history (χSB2 (14) = 2,887.93, CFI = 0.945, RMSEA = 0.121), but the alternative models we examined were not superior. Although factor structures in previous studies have varied considerably, we found a one-factor structure. Although internal consistency reliability was strong, factor analytic results did not further support the ISI. Inconsistencies in ISI measurement properties across studies may reflect differences in sample sizes and populations.

Correlates of plasma concentrations of per- and poly-fluoroalkyl substances among reproductive-aged Black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. METHODS: We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23-35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010-2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. RESULTS: PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (-34.7; -43.0, -25.1) and PFOA (-33.1; -39.2, -26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (-31.1; -37.8, -23.7), PFHxS (-24.2; -34.5, -12.3), and PFOS (-18.4; -28.3, -7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (-33.1; -39.6, -25.8), PFHxS (-29.3; -39.0, -18.1), PFNA (-25.2; -32.7, -16.8), and PFOS (-18.3; -28.3, -6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (-18.8; -28.3, -8.2), PFOS (-16.4; -24.9, -7.1), PFNA (-10.5; -17.8, -2.6), and PFOA (-10.0; -17.2, -2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4). CONCLUSIONS: Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use).

First- and second-degree family history of ovarian and breast cancer in relation to risk of invasive ovarian cancer in African American and white women.

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

Loneliness and mental health during the COVID-19 pandemic in older breast cancer survivors and noncancer controls.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had wide-ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. METHODS: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web-based or telephone COVID-19 survey, between May 27 and September 11, 2020. Mixed-effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies-Depression [CES-D] scale) from before to during the pandemic in survivors versus controls and to test survivor-control differences in the associations between changes in loneliness and changes in mental health, including depression (CES-D, excluding the loneliness item), anxiety (the State-Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID-19 death rates, and time between assessments. RESULTS: Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor-control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor-control differences. CONCLUSIONS: Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic.

A Prospective Ultrasound Study of Plasma Polychlorinated Biphenyl Concentrations and Incidence of Uterine Leiomyomata.

BACKGROUND: Uterine leiomyomata, or fibroids, are hormone-dependent neoplasms of the myometrium that can cause severe gynecologic morbidity. In previous studies, incidence of these lesions has been positively associated with exposure to polychlorinated biphenyls (PCBs), a class of persistent endocrine-disrupting chemicals. However, previous studies have been retrospective in design and none has used ultrasound to reduce disease misclassification. METHODS: The Study of Environment, Lifestyle, and Fibroids is a prospective cohort of 1,693 reproductive-aged Black women residing in Detroit, Michigan (enrolled during 2010-2012). At baseline and every 20 months for 5 years, women completed questionnaires, provided blood samples, and underwent transvaginal ultrasound to detect incident fibroids. We analyzed 754 baseline plasma samples for concentrations of 24 PCB congeners using a case-cohort study design. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals for the association between plasma PCB concentrations and ultrasound-detected fibroid incidence over a 5-year period. RESULTS: We observed little association between PCB congener concentrations and fibroid incidence. The HR for a one-standard deviation increase in log-transformed total PCBs was 0.94 (95% CI = 0.78, 1.1). The PCB congener with the largest effect estimate was PCB 187 (HR for a one-standard deviation increase in log-transformed exposure = 0.88, 95% CI = 0.73, 1.1). Associations did not seem to vary strongly across PCB groupings based on hormonal activity. CONCLUSIONS: In this cohort of reproductive-aged Black women, plasma PCB concentrations typical of the contemporary general population were not appreciably associated with higher risk of fibroids.

Correlates of Persistent Endocrine-Disrupting Chemical Mixtures among Reproductive-Aged Black Women.

Black women are exposed to multiple endocrine-disrupting chemicals (EDCs), but few studies have examined their profiles of exposure to EDC mixtures. We identified biomarker profiles and correlates of exposure to EDC mixtures in a cross-sectional analysis of data from a prospective cohort study of 749 Black women aged 23-35 years. We quantified plasma concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS) in nonfasting samples collected at baseline. Demographic, behavioral, dietary, and reproductive covariates were also collected at baseline. We used k-means clustering and principal component analysis (PCA) to describe concentration profiles of EDC mixtures (17 PCBs, 6 PBDEs, 4 OCPs, 6 PFAS), followed by multinomial logistic and multivariable linear regression to estimate mean differences in PCA scores (ß) and odds ratios (ORs) of cluster membership with their respective 95% confidence intervals (CIs). Older age (per 1 year increase: ß = 0.47, CI = 0.39, 0.54; OR = 1.27, CI = 1.20, 1.35), lower body mass index (per 1 kg/m2 increase: ß = -0.14, CI = -0.17, -0.12; OR = 0.91, CI = 0.89, 0.94), and current smoking (≥10 cigarettes/day vs never smokers: ß = 1.37, CI = 0.20, 2.55; OR = 2.63, CI = 1.07, 6.50) were associated with profiles characterized by higher concentrations of all EDCs. Other behaviors and traits, including dietary factors and years since last birth, were also associated with EDC mixtures.

Air pollution and breast cancer risk in the Black Women's Health Study.

BACKGROUND: Air pollution contains numerous carcinogens and endocrine disruptors which may be relevant for breast cancer. Previous research has predominantly been conducted in White women; however, Black women may have higher air pollution exposure due to geographic and residential factors. OBJECTIVE: We evaluated the association between air pollution and breast cancer risk in a large prospective population of Black women. METHODS: We estimated annual average ambient levels of particulate matter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) at the 1995 residence of 41,317 participants in the Black Women's Health Study who resided in 56 metropolitan areas across the United States. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for an interquartile range (IQR) increase in each pollutant. We evaluated whether the association varied by menopausal status, estrogen receptor (ER) status of the tumor and geographic region of residence. RESULTS: With follow-up through 2015 (mean = 18.3 years), 2146 incident cases of breast cancer were confirmed. Higher exposure to NO2 or O3 was not associated with a higher risk of breast cancer. For PM2.5, although we observed no association overall, there was evidence of modification by geographic region for both ER- (p for heterogeneity = 0.01) and premenopausal breast cancer (p for heterogeneity = 0.01). Among women living in the Midwest, an IQR increase in PM2.5 (2.87 µg/m3), was associated with a higher risk of ER- (HR = 1.53, 95% CI: 1.07-2.19) and premenopausal breast cancer (HR = 1.32, 95% CI: 1.03-1.71). In contrast, among women living in the South, PM2.5 was inversely associated with both ER- (HR = 0.74, 95% CI: 0.56-0.97) and premenopausal breast cancer risk (HR = 0.75, 95% CI: 0.62-0.91). DISCUSSION: Overall, we observed no association between air pollution and increased breast cancer risk among Black women, except perhaps among women living in the Midwestern US.

Aspirin use and risk of breast cancer in African American women.

BACKGROUND: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Few studies have investigated these associations among African American women. METHODS: To assess the relation of aspirin use to risk of breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort study of 59,000 African American women. On baseline and follow-up questionnaires, women reported regular use of aspirin (defined as use at least 3 days per week) and years of use. During follow-up from 1995 through 2017, 1919 invasive breast cancers occurred, including 1112 ER+, 569 ER-, and 284 triple-negative (TN) tumors. We used age-stratified Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+, ER-, and TN breast cancer, adjusted for established breast cancer risk factors. RESULTS: Overall, the HR for current regular use of aspirin relative to non-use was 0.92 (95% CI 0.81, 1.04). For ER+, ER-, and TN breast cancer, corresponding HRs were 0.98 (0.84, 1.15), 0.81 (0.64, 1.04), and 0.70 (0.49, 0.99), respectively. CONCLUSIONS: Our findings with regard to ER- and TN breast cancer are consistent with hypothesized inflammatory mechanisms of ER- and TN breast cancer, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- and TN breast cancer.

Dietary Fat Intake and Risk of Uterine Leiomyomata: A Prospective Ultrasound Study.

Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced ω-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010-2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and trans-fat were not appreciably associated with UL incidence. Intake of the marine ω-3 polyunsaturated fatty acid, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: hazard ratio = 1.49, 95% confidence interval: 1.04, 2.14; P for trend = 0.01). Intakes of total marine ω-3 polyunsaturated fatty acids were similarly associated with elevated UL incidence (hazard ratio = 1.35, 95% confidence interval: 0.94, 1.93; P for trend = 0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association.

Correlates of organochlorine pesticide plasma concentrations among reproductive-aged black women.

BACKGROUND: Organochlorine pesticides (OCPs) are lipophilic persistent organic pollutants associated with adverse health outcomes. Black women have higher body burdens compared with other U.S. populations and research on their correlates is limited. METHODS: Using baseline data from a prospective cohort study of Black women aged 23-35 years from the Detroit, Michigan metropolitan area (enrolled 2010-2012), we examined correlates of plasma concentrations of the following OCPs: dichlorodiphenyltrichloroethane (p,p'-DDE), hexachlorobenzene (HCB), oxychlordane, and trans-nonachlor. At enrollment, we collected non-fasting blood samples from 742 participants. We also collected data on demographic, behavioral, dietary, occupational, and medical history factors via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent (%) differences across categories of each correlate and 95% confidence intervals (CIs). RESULTS: In models adjusted for all other correlates, a 5-year increase in age was associated with 24% higher oxychlordane (95% CI: 12%, 38%) and 26% higher trans-nonachlor (95% CI: 12%, 42%) plasma concentrations. Heavy alcohol use was associated with 7-9% higher plasma concentrations of p,p'-DDE, oxychlordane, and trans-nonachlor. Current smoking was associated with 10-19% higher plasma concentrations of all four OCPs, and was highest for current smokers of ≥10 cigarettes/day (% differences ranged from 22 to 29%). Compared with having never been breastfed during infancy, having been breastfed for ≥3 months was associated with 15% higher concentrations of p,p'-DDE (95% CI: 6%, 25%), 14% higher oxychlordane (95% CI: 5%, 24%), and 15% higher trans-nonachlor (95% CI: 5%, 27%). Consumption of ≥5 vs. ≤2 glasses/day of tap or bottled water was associated with 8-15% higher plasma concentrations of all four OCPs, and was highest for trans-nonachlor (% difference: 15%; 95% CI: 6%, 26%). No other dietary predictors were appreciably associated with plasma OCP concentrations. Obesity, parity, higher birth order, and longer lactation duration were inversely associated with plasma OCP concentrations. CONCLUSIONS: In Black U.S. women of reproductive age, older age was an important correlate of plasma OCP concentrations. Exposure to OCPs earlier in life appears to contribute to current blood concentrations. In addition, tobacco, alcohol, and drinking water may be important sources of exposure.

Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: a resource of harmonized data from eight epidemiologic studies of African American and white women.

PURPOSE: Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. METHODS: We harmonized risk factors and prognostic characteristics from eight U.S. STUDIES: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). RESULTS: Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. CONCLUSION: OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.