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Physical activity (PA) is associated with decreased signaling in the mTOR pathway in animal models of mammary cancer, which may indicate favorable outcomes. We examined the association between PA and protein expression in the mTOR signaling pathway in breast tumor tissue. Data on 739 patients with breast cancer, among which 125 patients had adjacent-normal tissue, with tumor expression for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-P70S6K were analyzed. Self-reported recreational PA levels during the year prior to diagnosis were classified using the Centers for Disease Control and Prevention guideline as sufficient (for moderate or vigorous) PA or insufficient PA (any PA but not meeting the guideline) or no PA. We performed linear models for mTOR protein and two-part gamma hurdle models for phosphorylated proteins. Overall, 34.8% of women reported sufficient PA; 14.2%, insufficient PA; 51.0%, no PA. Sufficient (vs. no) PA was associated with higher expression for p-P70S6K [35.8% increase; 95% confidence interval (CI), 2.6–80.2] and total phosphoprotein (28.5% increase; 95% CI, 5.8–56.3) among tumors with positive expression. In analyses stratified by PA intensity, sufficient versus no vigorous PA was also associated with higher expression levels of mTOR (beta = 17.7; 95% CI, 1.1–34.3) and total phosphoprotein (28.6% higher; 95% CI, 1.4–65.0 among women with positive expression) in tumors. The study found that guideline-concordant PA levels were associated with increased mTOR signaling pathway activity in breast tumors. Studying PA in relation to mTOR signaling in humans may need to consider the complexity of the behavioral and biological factors.Significance:PA increases energy expenditure and limits energy utilization in the cell, which can influence the mTOR pathway that is central to sensing energy influx and regulating cell growth. We studied exercise-mediated mTOR pathway activities in breast tumor and adjacent-normal tissue. Despite the discrepancies between animal and human data and the limitations of our approach, the findings provide a foundation to study the mechanisms of PA and their clinical implications.

Background: Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later. Methods: 504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models. Results: Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient ( Conclusions: Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis. Impact: Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Supplementary Table from Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study

Supplementary Figure from Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study

Background:Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later.Methods:504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models.Results:Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient (Conclusions:Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis.Impact:Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Supplemental Table 5 reports the association without adjusting BMI as a sensitivity analysis.

Supplemental Table 8 reported stratified analysis for obesity and normal weight/overweight.

Supplemental Table 7 reported stratified analysis for Black and White race.

Supplemental Table 2 shows protein expression in breast cancer tissue and paired adjacent normal tissue.

Supplemental Table 4 shows the associations adjusting covariates and total energy intake.

Supplemental Table 9 reported stratified analysis for postmenopausal and premenopausal women.

Supplemental Table 14 reported stratified analysis for ER+ tumors and ER- tumors.

Physical activity (PA) is associated with decreased signaling in the mTOR pathway in animal models of mammary cancer, which may indicate favorable outcomes. We examined the association between PA and protein expression in the mTOR signaling pathway in breast tumor tissue. Data on 739 patients with breast cancer, among which 125 patients had adjacent-normal tissue, with tumor expression for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-P70S6K were analyzed. Self-reported recreational PA levels during the year prior to diagnosis were classified using the Centers for Disease Control and Prevention guideline as sufficient (for moderate or vigorous) PA or insufficient PA (any PA but not meeting the guideline) or no PA. We performed linear models for mTOR protein and two-part gamma hurdle models for phosphorylated proteins. Overall, 34.8% of women reported sufficient PA; 14.2%, insufficient PA; 51.0%, no PA. Sufficient (vs. no) PA was associated with higher expression for p-P70S6K [35.8% increase; 95% confidence interval (CI), 2.6–80.2] and total phosphoprotein (28.5% increase; 95% CI, 5.8–56.3) among tumors with positive expression. In analyses stratified by PA intensity, sufficient versus no vigorous PA was also associated with higher expression levels of mTOR (beta = 17.7; 95% CI, 1.1–34.3) and total phosphoprotein (28.6% higher; 95% CI, 1.4–65.0 among women with positive expression) in tumors. The study found that guideline-concordant PA levels were associated with increased mTOR signaling pathway activity in breast tumors. Studying PA in relation to mTOR signaling in humans may need to consider the complexity of the behavioral and biological factors.Significance:PA increases energy expenditure and limits energy utilization in the cell, which can influence the mTOR pathway that is central to sensing energy influx and regulating cell growth. We studied exercise-mediated mTOR pathway activities in breast tumor and adjacent-normal tissue. Despite the discrepancies between animal and human data and the limitations of our approach, the findings provide a foundation to study the mechanisms of PA and their clinical implications.

Supplemental Table 3 shows protein expression distribution in adjacent normal tissue by PA level.

List of Disease and Phenotype Associations used to Generate list of GWAS genes used to prioritize immune pathways

Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk.Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index.Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype.Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes.Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.

Description of Study Populations in AMBER Consortium

Immune-related genes found to be associated with breast cancer in AMBER

Supplemental Table S1. Pooled Odds Ratios and 95% Confidence Intervals Representing the Association Between Physical Inactivity and Epithelial Ovarian Cancer by Menopause Status. Supplemental Table S2. Age-Adjusted And Multivariable-Adjusted Pooled Odds Ratios And 95% Confidence Intervals (CI) Representing The Association Between Physical Inactivity And Epithelial Ovarian Cancer By Race. Supplemental Table S3. Pooled odds ratios and 95% confidence intervals representing the association between physical inactivity and epithelial ovarian cancer by standard BMI classification. Supplemental Table S4. Pooled odds ratios and 95% confidence intervals representing the association between physical inactivity and epithelial ovarian cancer by dichotomous BMI classification

Background: African American (AA) women have higher incidence of aggressive, young-onset (Methods: We examined tumor characteristics and breast cancer risk factors associated with premenopausal young (Results: Premenopausal AA women Conclusions: Among premenopausal AA women, diagnosis before age 40 is associated with more aggressive breast tumor biology and some etiologic differences.Impact: Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1722–9. ©2017 AACR.

Supplemental Table 1. Covariate characteristics of cases controls in the AMBER Consortium stratified by study; Supplemental Table 2. Recent alcohol intake (drinks per week) in relation to invasive breast cancer stratified by smoking status in the AMBER Consortium; Supplemental Table 3. Recent alcohol intake (drinks per week) in relation to invasive breast cancer stratified by lifetime duration of oral contraceptive use in the AMBER consortium; Supplemental Table 4. Recent alcohol intake (drinks per week) in relation to invasive breast cancer stratified by menopausal status in the AMBER consortium; Supplemental Figure 1. Flexible modeling of drinks per week as a squared term versus the log odds (95% confidence interval) of breast cancer in the AMBER consortium

Case-control ORs of breast cancer risk factors by ER status among young (

Background: Constitutional immunity shaped by exposure to endemic infectious diseases and parasitic worms in Sub-Saharan Africa may play a role in the etiology of breast cancer among African American (AA) women.Methods: A total of 149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based pathway analyses were conducted using the adaptive rank truncated product statistic for overall breast cancer risk, and risk by estrogen receptor (ER) status. Unconditional logistic regression analysis was used to estimate ORs and 95% confidence intervals (CIs) for single variants.Results: The top pathways were Interleukin binding (P = 0.01), Biocarta TNFR2 (P = 0.005), and positive regulation of cytokine production (P = 0.024) for overall, ER+, and ER− cancers, respectively. The most significant gene was IL2RB (P = 0.001) for overall cancer, with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79–0.92). Only BCL3 contained a significant variant for ER+ breast cancer. Variants in IL2RB, TLR6, IL8, PRKDC, and MAP3K1 were associated with ER− disease. The only genes showing heterogeneity between ER− and ER+ cancers were TRAF1, MAP3K1, and MAPK3 (P ≤ 0.02). We also noted genes associated with autoimmune and atopic disorders.Conclusions: Findings from this study suggest that genetic variants in immune pathways are relevant to breast cancer susceptibility among AA women, both for ER+ and ER− breast cancers.Impact: Results from this study extend our understanding of how inherited genetic variation in immune pathways is relevant to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 27(3); 321–30. ©2018 AACR.

The NanoString GeoMx digital spatial profiling is a new multiplexed platform that quantifies the abundance of tumor‐ and immune‐related proteins in a spatially resolved manner. We performed DSP for the simultaneous assessment of 52 analytes within spatially resolved tissue compartments defined by pan‐cytokeratin expression. We compared protein targets between 94 African American/Black and 65 European American/White cases, tumor and stromal tissue compartments, estrogen receptor alpha (ER)‐positive and ER‐negative cases, and explored potential biomarkers of survival. Of 33 analytes with robust signal for analysis, results were highly replicable. For a subset of markers, correlative analyses between DSP analytes and traditional immunohistochemistry scores revealed moderate to very strong associations between the two platforms. Similarly, DSP analytes and gene expression scores were concordant for 21 of 25 markers with overlap between the two datasets. Several analytes varied by ER status, and across the 25 immune markers surveyed, 14 had a significant inverse association with ER expression. B7 homolog 3 (B7‐H3; encoded by CD276) was the only analyte to show a significant difference by race, being lower in both the tumor and stromal compartments in Black women. DSP markers that were associated with survival included CD8, CD25, CD56, CD127, EpCAM, ER, Ki‐67, and STING. We conclude that DSP is an efficient tool for screening tumor‐ and immune‐related markers in a simultaneous fashion and yields results that are concordant with established immune profiling assays. DSP immune analytes were inversely associated with ER expression, in agreement with a substantial body of previous work that documents higher immune infiltration in ER‐negative breast cancers. This technology revealed that scores of the B7‐H3 protein were significantly lower in breast cancers from Black women compared with White women, an intriguing finding that requires replication in independent and racially diverse female populations., We evaluated the NanoString GeoMx digital spatial profiling platform for highly multiplexed immune profiling in a population of Black and White women with invasive breast cancer. Using DSP for discovery and conventional immunohistochemistry and gene expression data for validation, we found the DSP technology to be efficient, reproducible, and to yield results that are concordant with established immune profiling assays.

Background Mounting evidence supports associations between objective neighborhood disorder, perceived neighborhood disorder, and health, yet alternative explanations involving socioeconomic and neighborhood social cohesion have been understudied. We tested pathways between objective and perceived neighborhood disorder, perceived neighborhood social cohesion, and socioeconomic factors within a longitudinal cohort. Methods Demographic and socioeconomic information before diagnosis was obtained at interviews conducted approximately 10 months post-diagnosis from participants in the Women’s Circle of Health Follow-up Study – a cohort of breast cancer survivors self-identifying as African American or Black women (n = 310). Neighborhood perceptions were obtained during follow-up interviews conducted approximately 24 months after diagnosis. Objective neighborhood disorder was from 9 items audited across 23,276 locations using Google Street View and scored to estimate disorder values at each participant’s residential address at diagnosis. Census tract socioeconomic and demographic composition covariates were from the 2010 U.S. Census and American Community Survey. Pathways to perceived neighborhood disorder were built using structural equation modelling. Model fit was assessed from the comparative fit index and root mean square error approximation and associations were reported as standardized coefficients and 95% confidence intervals. Results Higher perceived neighborhood disorder was associated with higher objective neighborhood disorder (β = 0.20, 95% CI: 0.06, 0.33), lower neighborhood social cohesion, and lower individual-level socioeconomic factors (final model root mean square error approximation 0.043 (90% CI: 0.013, 0.068)). Perceived neighborhood social cohesion was associated with individual-level socioeconomic factors and objective neighborhood disorder (β = − 0.11, 95% CI: − 0.24, 0.02). Conclusion Objective neighborhood disorder might be related to perceived disorder directly and indirectly through perceptions of neighborhood social cohesion.

Breast cancer is the leading cause of death among Hispanic women. The number of Hispanic breast cancer survivors is increasing because the US Hispanic population is fast-growing and breast cancer survival is improving. However, this vulnerable population has received little attention. Obesity and weight gain affect Hispanic and African American/Black women disproportionately. Obesity affects several factors relevant to cancer survivorship, including cancer treatment and patient-reported outcomes such as health-related quality of life (QoL). As a first step toward addressing these issues, a pilot study was conducted to assess the feasibility of assembling a cohort of Hispanic breast cancer survivors in New Jersey. Methods were similar to those used in the ongoing Women’s Circle of Health Follow-Up Study, a cohort of African American/Black breast cancer survivors in New Jersey. Hispanic breast cancer survivors were very interested and willing to participate. There were interesting differences in body mass index and central adiposity between Hispanic and African American/Black breast cancer survivors, but both groups had a high prevalence of body fatness and comorbidities. Hispanic breast cancer survivors had lower QoL, particularly obese women. More research is needed to understand survivorship needs in minority and medically underserved women after a breast cancer diagnosis.

Background The mechanistic target of rapamycin (mTOR) pathway promoted by positive energy imbalance and insulin-like growth factors can be a mechanism by which obesity influences breast cancer risk. We evaluated the associations of body fatness with the risk of breast cancer varied with phosphorylated (p)-mTOR protein expression, an indication of the pathway activation. Methods Women with newly diagnosed breast cancer (n = 715; 574 [80%] Black and 141 [20%] White) and non-cancer controls (n = 1983; 1280 [64%] Black and 713 [36%] White) were selected from the Women’s Circle of Health Study. Surgical tumor samples among the cases were immunostained for p-mTOR (Ser2448) and classified as p-mTOR-overexpressed, if the expression level ≥ 75th percentile, or p-mTOR-negative/low otherwise. Anthropometrics were measured by trained staff, and body composition was determined by bioelectrical impedance analysis. Odds ratios (ORs) of p-mTOR-overexpressed tumors and p-mTOR-negative/low tumors compared to controls were estimated using polytomous logistic regression. The differences in the associations by the p-mTOR expression status were assessed by tests for heterogeneity. Results Cases with p-mTOR-overexpressed tumors, but not cases with p-mTOR-negative/low tumors, compared to controls were more likely to have higher body mass index (BMI), percent body fat, and fat mass index (P-heterogeneity P-heterogeneity = 0.27 and 0.48, respectively). Conclusions Our findings suggest that in this population composed of predominately Black women, body fatness is associated with breast cancer differently for p-mTOR overexpression and p-mTOR negative/low expression. Whether mTOR plays a role in the obesity and breast cancer association warrants confirmation by prospective studies.

Background: In preclinical models of breast cancer (BC), chronic stress enhances tumor growth and metastasis through β-adrenergic signaling as part of the “fight or flight” stress response pathway. These effects involve norepinephrine-mediated sympathetic regulation of cancer-related immunity. In a novel discovery, adrenergic stress in tumor-bearing mouse models of BC was associated with symptoms of intense cold discomfort, reduced CD8+ T cells, and higher immunosuppressive myeloid derived suppressor cells (MDSC) and regulatory T cells. BC survivors often experience heightened sympathetic activation and anecdotally report symptoms of feeling overly cold. Based on preclinical findings, symptoms of cold discomfort reported by BC survivors are hypothesized to identify those with reduced anti-cancer immunity and increased immunosuppression. Methods: Women with incident stage I to III BC were prospectively enrolled into the Women’s Health after Breast Cancer Study prior to BC treatment at Roswell Park Comprehensive Cancer Center. Participants provided blood samples and completed a survey assessing BC risk factors at the time of diagnosis and survivorship outcomes one-year post. Symptoms of being persistently and inappropriately cold as well as the occurrence of hot flashes and sweats were assessed using a Likert scale patterned on the validated Multidimensional Assessment of Fatigue Scale. A total of 424 women who had questionnaire data and plasma samples were included in the study. A panel of 27 Th1, Th2, Th9, and Th17 cytokines were assayed using a multiplex Luminex bead-based approach. Perceived symptoms of thermal discomfort were evaluated using logistic regression over cytokine tertiles (T1, T2, T3). Principal component analysis (PCA) was used to identify clusters of cytokines associated with symptoms of thermal discomfort. Cytokine composite scores were further refined based on their role with anti-tumor or pro-tumor activity. Multivariate models were adjusted for age, race, menopausal status, body mass index, stage, estrogen receptor status, grade, and treatment received. Results: Forty-six percent (195/424) of patients reported symptoms of feeling cold while 65% (275/424) experienced hot flashes and night sweats. There were no differences in patient or tumor characteristics between women who reported feeling cold versus those who did not, with women receiving chemotherapy more likely to report feeling cold (p = 0.01). Importantly, menopausal onset occurring after BC diagnosis or receipt of hormonal therapy were not associated with symptoms of feeling cold, but as expected were associated with experiencing hot flashes indicating that feeling cold is a distinct symptom from hot flashes. Higher pre-treatment levels of IL-6 was associated with 40-55% lower risk of feeling inappropriately cold 1-year post-diagnosis (T3 vs T1: OR=0.58, 95% CI: 0.34-1.00, p=0.01). PCA analysis identified a composite cytokine score at 1-year post diagnosis, which included the Th1 cytokines IL-12p70 and TNFα, IL-9 and IL-21 as cytokines involved in Th9 antitumor immunity, and the type 3 interferon IFN-λ2/IL-28α, which are all associated with increased CD8+ T cell activity. Increased scores were associated with reduced odds of feeling cold (T3 vs T1: OR=0.42, 95% CI: 0.23-0.77, p=0.02). Hot flashes in contrast were not associated with individual cytokine levels or composite scores. Conclusions: Symptoms of cold discomfort are less likely to be reported by BC survivors with a composite cytokine pattern associated with increased anti-tumor immunity. Further research is needed to determine if this symptom is associated with increased adrenergic stress and worse BC outcomes as observed in preclinical models. Citation Format: Shipra Gandhi, Maithreyi Sarma, Kristopher Attwood, Christine B. Ambrosone, Elizabeth A. Repasky, Chi-Chen Hong. Symptoms of cold discomfort are reduced in breast cancer patients with a composite cytokine pattern associated with increased anti-tumor immunity [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-16.

Background: The disproportionate burden of more aggressive breast cancer subtypes among African American/Black women may stem from multilevel determinants. However, data are limited regarding the impacts of neighborhood social environmental characteristics among Black women. Methods: We evaluated the association between neighborhood-level socioeconomic status (nSES) and breast cancer subtypes in the Women's Circle of Health and Women's Circle of Health Follow-up Study, which included 1,220 Black women diagnosed from 2005 to 2017 with invasive breast cancer. nSES at diagnosis was measured using NCI's census tract-level SES index. We used multilevel multinomial logistic regression models to estimate the association of nSES with breast cancer subtypes [triple-negative breast cancer (TNBC), HER2-positive vs. luminal A], adjusting for individual-level SES, body mass index, and reproductive factors. We tested for interactions by neighborhood racial composition. Results: Compared with census tracts characterized as high nSES, the relative risk ratios (RRR) for TNBC were 1.81 [95% confidence interval (CI): 1.20–2.71] and 1.95 (95% CI: 1.27–2.99) for women residing in areas with intermediate and low nSES, respectively (Ptrend = 0.002). Neighborhood racial composition modified the association between nSES and TNBC; the highest relative risk of TNBC was among women residing in low nSES areas with low proportions of Black residents. Conclusions: Black women residing in socioeconomically disadvantaged neighborhoods may have an increased risk of TNBC, particularly in areas with lower proportions of Black residents. Impact: Places people live may influence breast tumor biology. A deeper understanding of multilevel pathways contributing to tumor biology is needed.

PURPOSE: Diabetes and hypertension are two common comorbidities that affect breast cancer patients, particularly Black women. Disruption of chronic disease management during cancer treatment has been speculated. Therefore, this study examined the implementation of clinical practice guidelines and health outcomes for these comorbidities before and during cancer treatment. METHODS: We used a population-based, prospective cohort of Black women diagnosed with breast cancer (2012–2016) in New Jersey (N=563). Chronic disease management for diabetes and hypertension were examined 12-months before and after breast cancer diagnosis and compared using McNemar’s test for matched paired and paired t-tests. RESULTS: Among this cohort, 18.1% had a co-diagnosis of diabetes and 47.2% had a co-diagnosis of hypertension. Implementation of clinical practice guidelines and health outcomes that differed in the 12-months before and after cancer diagnosis included: lipid screening (64.5% before versus 50.0% after diagnosis; p=0.004), glucose screening (72.7% versus 90.7%; p

Background:Evidence suggests etiologic heterogeneity among breast cancer subtypes. Previous studies with six-marker IHC classification of intrinsic subtypes included small numbers of black women.Methods:Using centralized laboratory results for estrogen receptor (ER), progesterone receptor, HER2, proliferation marker, Ki-67, EGFR, and cytokeratin (CK)5/6, we estimated case-only and case–control ORs for established breast cancer risk factors among cases (n = 2,354) and controls (n = 2,932) in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. ORs were estimated by ER status and intrinsic subtype using adjusted logistic regression.Results:Case-only analyses by ER status showed etiologic heterogeneity by age at menarche, parity (vs. nulliparity), and age at first birth. In case–control analyses for intrinsic subtype, increased body mass index and waist-to-hip ratio (WHR) were associated with increased risk of luminal A subtype, whereas older age at menarche and parity, regardless of breastfeeding, were associated with reduced risk. For basal-like cancers, parity without breastfeeding and increasing WHR were associated with increased risk, whereas breastfeeding and age ≥25 years at first birth were associated with reduced risk among parous women. Basal-like and ER−/HER2+ subtypes had earlier age-at-incidence distribution relative to luminal subtypes.Conclusions:Breast cancer subtypes showed distinct etiologic profiles in the AMBER consortium, a study of more than 5,000 black women with centrally assessed tumor biospecimens.Impact:Among black women, high WHR and parity without breastfeeding are emerging as important intervention points to reduce the incidence of basal-like breast cancer.

PurposeThe diagnosis and treatment of cancer can result in an array of psychological and physical sequelae for patients. Mindfulness-Based Stress Reduction (MBSR) is a well-validated intervention aimed at reducing emotional distress and improving long-term treatment effects in cancer patients. Further studies employing more powerful control group designs are needed to validate MBSR in patients with advanced disease and in novel clinical settings that facilitate enrollment. Patients diagnosed with metastatic disease are highly impacted by their disease and treatment and are an under-examined high-risk population. Methods This study aimed to determine the efficacy of a 6-week modified online MBSR intervention in improving psychological and physical symptoms associated with quality-of-life, as well as biomarkers associated with their disease trajectory, in patients diagnosed with metastatic breast cancer. Results The 6-week online intervention was found to significantly improve measures of mindfulness and several psychological/quality of life indices. There were no intervention effects on biomarkers of stress or inflammation, although improved levels of mindfulness due to the intervention were negatively correlated with several pro-inflammatory cytokines, including IL-6, IL-8, and TNFα. Patients indicated high satisfaction with the content and delivery method of the intervention. Conclusions Addressing the multidimensional needs of metastatic patients requires service delivery models that integrate powerful interventions into care settings while minimizing participant burden. This study developed a novel online MBSR treatment for distressed metastatic breast cancer patients that was found to be effective in improving mindfulness and several areas pertinent to patient quality of life.

PURPOSE Unfavorable weight change after breast cancer diagnosis increases the risk of mortality, but individual and neighborhood risk factors affecting postdiagnosis weight and body fat changes are unclear among Black women, who have higher rates of obesity and mortality than any other racial/ethnic group. METHODS Adiposity changes during the period approximately 10 months-24 months after diagnosis were evaluated among 785 women diagnosed between 2012 and 2018 and enrolled in the Women's Circle of Health Follow-Up Study, a population-based prospective cohort of Black breast cancer survivors in New Jersey. Multilevel factors for weight and fat mass change (with gain or loss defined as a relative difference of 3% or more, and considering whether changes were intentional or unintentional) were estimated using multivariable polytomous logistic regressions and multilevel models. RESULTS Adiposity gain was prevalent: 28% and 47% gained weight and body fat, respectively, despite a high baseline prevalence of overweight or obesity (86%). Risk factors for fat mass gain included receiving chemotherapy (relative risk ratio: 1.59, 95% CI, 1.08 to 2.33) and residing in neighborhoods with a greater density of fast-food restaurants (relative risk ratio comparing highest with lowest tertile: 2.18, 95% CI, 1.38 to 3.46); findings were similar for weight gain. Only 9% of women had intentional weight loss, and multilevel risk factors differed vastly from unintentional loss. CONCLUSION Both individual and neighborhood factors were associated with adiposity change among Black breast cancer survivors. Residential environment characteristics may offer clinically meaningful information to identify cancer survivors at higher risk for unfavorable weight change and to address barriers to postdiagnosis weight management.

This study tested spatio-temporal model prediction accuracy and concurrent validity of observed neighborhood physical disorder collected from virtual audits of Google Street View streetscapes. We predicted physical disorder from spatio-temporal regression Kriging models based on measures at three dates per each of 256 streestscapes (n = 768 data points) across an urban area. We assessed model internal validity through cross validation and external validity through Pearson correlations with respondent-reported perceptions of physical disorder from a breast cancer survivor cohort. We compared validity among full models (both large- and small-scale spatio-temporal trends) versus large-scale only. Full models yielded lower prediction error compared to large-scale only models. Physical disorder predictions were lagged at uniform distances and dates away from the respondent-reported perceptions of physical disorder. Correlations between perceived and observed physical disorder predicted from the full model were higher compared to that of the large-scale only model, but only at locations and times closest to the respondent's exact residential address and questionnaire date. A spatio-temporal Kriging model of observed physical disorder is valid.

PURPOSE: Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology is not well understood. METHODS: NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks). RESULTS: Black race was associated with lower gene expression of LEPR (P=0.002) and ADIPOR1 (P=0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P=0.0007, P