Women's Circle Research Articles

The social lives of married women: Peer effects in female autonomy and investments in children

In patriarchal societies, sticky norms affect married women's social circles, their autonomy, and the outcomes of intra-household bargaining. This paper uses primary data on women's social networks in Uttarakhand, India; the modal woman has only three friends, and over 80 percent do not have any friends of another caste. This paper examines the effect of a shock to friends' empowerment on a woman's autonomy, specifically physical mobility, access to social safety nets, and employment outside the household; perceived social norms; and an outcome of household bargaining: investments in her children. The analysis instruments for endogenous network formation using a woman's age and her caste network in the village. The key peer effect is the impact of having a friend who received an empowerment shock on a woman who did not receive that shock. The results show significant peer effects on only a few of the examined measures of women's autonomy. In contrast, peer effects exist on all considered outcomes of a daughters' diet and time spent on chores. The findings suggest a large decay rate between effects on own empowerment and peer effects. Interventions targeting child welfare through women's empowerment may generate second-order effects on intra-household decision-making, albeit with substantial decay rates, and thus benefit from targeted rather than randomized rollout. In contrast, interventions on gender roles and women's autonomy may be limited by the stickiness of social norms.

From Tupperware to Scentsy: The gendered culture of women and direct sales

AbstractConsumer culture has transformed the lives of working women and family life for well over a century. Perhaps one of the most gender distinct forms of consumer culture introduced in the 20th century was the direct sales industry. The business model of direct sales depends on women's social circles as a means to market products directly to consumers, antithetical to retail spaces of malls and shopping outlets. In this literature review, I explore how women construct meaning behind products in this sales culture, while examining the emotional investment that women make as direct sales consultants and the personal outcomes of this investment. To begin, I include a brief history of the direct sales industry with a focus on three pioneering companies: Avon, Tupperware, and Mary Kay as foundational to women's contributions and involvement in the industry today. Next, I explore the pathways that motivate women's draw to direct selling as a form of emotional labor that allows them to balance professional work and family life while yielding minimal financial gain. I analyze the messaging of direct sales companies that cleverly speak directly to women's needs for recognition and assist in constructing personal identity and self‐worth. Finally, I examine trends for the future of direct sales companies as they look to maintain relevance through global markets and brand recognition that will expand beyond women's social circles and parties.

Abstract P4-06-05: PanCancer profiling reveals population difference in breast cancer immune microenvironment

Abstract BACKGROUND. Breast Cancer (BC) outcome in patients (pts) of African ancestry (AA) is worse than pts of European ancestry (EA) despite accounting for socioeconomic status and access. AA have higher hormone receptor negative (HR-) and Triple Negative (TNBC) tumors, subtypes associated with stronger presence of tumor infiltrating lymphocytes (TILs). We hypothesize that BC Immune Microenvironment (IME) composition differs by ancestry, and describe IME from two independent datasets. METHODS. Transcriptome data from the Cancer Genome Atlas (TCGA) (Group 1, Gp1) were used to estimate 22 IME cell types in BC samples by CIBERSORT. Clinical and overall survival (OS) data were accessed from XENA. Gp2 tissue samples were obtained from Women's Circle of Health study and Pathology Resource Network at Roswell Park Comprehensive Cancer Center and processed using NanoString™ PanCancer Immune Profiling panel, consisting of 770 immunity-related genes describing 24 IME cell types. Immune Dysfunction and Exclusion (TIDE) scores were derived from an algorithm by Jiang et al. RESULTS. Gp1 consisted of 183 AA and 752 EA, with median age older in EA (54.5 vs 59). On CIBERSORT IME analysis by race, AA had higher IME infiltrates including macrophages (Mp), dendritic cells (DC) and TILs; notably T regulatory (Treg) and T Follicular Helper (Tfh) cells. The ratios of Tregs and Tfh to total TILs were also elevated. When stratified by subtypes, AAs with TNBC/Basal-like BC had higher Tregs and Tfh cells. CD8+ cells were higher in HR+ and high-grade AA pts only. CD4+/total T-cells was higher in AA across all subtypes, and predicted worse OS (HR 3.15[1.07-9.2]). Gp2 had 190 AA and 177 EA with comparable median age at diagnosis (53 versus 54) and tumor grade. By subtype, TNBC had significantly higher total TILs, CD45+, CD8+, exhausted CD8+, Treg, cytotoxic T cells, B, natural killer (NK), activated NK, DC and Mp; yet significantly lower mast cells and neutrophils (p <0.01). CD8+/Exhausted CD8+ and CD8+/Treg ratios were lower in TNBC and higher-grade tumors, and lowest in HR- grade III. Most of immune pathways were enriched in HR- tumors, with only exception being cell cycle genes being remarkably enriched in HR+ tissues (p <0.01). TIDE demonstrated high immune dysfunction in HR- and high exclusion in HR+ tumors. When compared to EA, AA had more TILs, including B, cytotoxic T-cells, exhausted CD8+, NK, activated NK and Tregs (p <0.01). Neutrophils, Mp and CD8+ were higher in EA. EA also had significantly higher ratio of immune cell types to total TILs across cytotoxic, exhausted CD8+ and Tregs, as well as persistent higher neutrophils, Mp and CD8+ ratios. CD8+/Treg ratio was higher in EA. Consistent with Gp1; CD4+/total T-cell ratio was higher in AA across all subtypes. CONCLUSION. IME differed significantly by HR, grade and ancestry. Aggressive BC demonstrated stronger overall immune response but dysfunctional IME phenotype (higher Treg, lower granulocytes and mast cells ratios). AA had more TILs across all subtypes, but lower ratios of activator (CD8+, Cytotoxic) to suppressor TILs (Treg, exhausted CD8+), demonstrating immune tolerance and immune-desert model, exception being persistently high fraction of CD4+ ratio predicting worse OS. Citation Format: Elkhanany A, Takabe K, Khoury T, Omilian A, Cheng D, Katsuta E, Davis W, Yan L, Hong C-C, Bandera E, Ambrosone C, Yao S. PanCancer profiling reveals population difference in breast cancer immune microenvironment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-05.

Oko poetki. Uwagi o twórczości Ewy Elżbiety Nowakowskiej

The article describes the work of the poet from Cracow,the author of short stories, essayist and translator – Ewa Elżbieta Nowakowska. Her poems were situated on the map of Polish literature among the “born in the seventies”, in the strand of “emboldened imagination” poetry, in the background of “Cracow school of poetry”, in a circle of women’s poetry. The main themes of her work: religion, the world of nature, history, culture and were presented by selecting relevant examples of her poems. In the conclusion, it was hypothesized that the varied work of the poet combines with the interest in perception and cognition, for what is available for the sense of sight as well as for what is hidden: transcendence and the mystery of being, expressed in the poet’s works by the broad metaphor of “the eye”.

Abstract A57: Validity of self-reported body mass index among African American breast cancer survivors: The Women's Circle of Health Follow-Up Study

Abstract Background: Compared to interviewer-measured, self-reported weight and height are oftentimes less burdensome to participants and less costly in epidemiologic studies. Validity studies of body mass index (BMI) based on self-reported weight and height have shown that individuals commonly underestimate their BMI, but the accuracy varies by participants' characteristics such as weight status and race/ethnicity. However, information is lacking on the validity of self-reported BMI among African American breast cancer survivors, who are known to have a high prevalence of obesity. Objective: The primary objective of this study was to evaluate the validity of BMI, based on self-reported weight and height, among African American breast cancer survivors. The secondary aim was to identify factors associated with BMI misreporting. Methods: The Women's Circle of Health Follow-Up Study is an ongoing population-based longitudinal study of African American breast cancer survivors in New Jersey. Eligible participants at baseline include self-identified African American women aged 20 to 75 years, with histologically confirmed breast cancer diagnosis. Active follow-up visits are ongoing to obtain updated information including self-reported and interviewer-measured anthropometric data. To date, 243 women completed the follow-up 1 visit and their self-reported and interviewer-measured anthropometric data were available for comparison. Pearson correlation and Cohen's kappa coefficients were used to describe the relationship between self-reported and interviewer-measured BMI (at follow-up 1) as continuous and categorical, respectively. Multinomial logistic regressions were used to identify factors associated with reporting accuracy. We also evaluated the associations of self-reported and interviewer-measured BMI with obesity-related health outcomes, using hypertension as an example, to evaluate the impact of potential misreporting. Results: The mean difference (standard deviation) between self-reported and measured BMI was -0.41 (1.49) kg/m2. Self-reported and interviewer-measured BMI values were highly correlated among all participants (r = 0.97) and when stratified by participants' characteristics (e.g., age, smoking, tumor grade; all r >0.90). The agreement between BMI categories (i.e., normal weight, overweight, obese I, II, and III) based on self-reported and interviewer-measured data was good (kappa = 0.75). Women who were older, had higher-grade tumors, and had greater BMI, percent body fat, and waist-to-hip ratio were more likely to under-report their BMI by ≥3%. Women who were current smokers, had higher-grade and ER-negative tumors, and had lower BMI and percent body fat were more likely to over-report by ≥3%. The BMI-hypertension association was similar using self-reported BMI (OR per 5 kg/m2 increase: 1.63; 95% CI: 1.27-2.10) and measured BMI (OR per 5 kg/m2 increase: 1.58; 95% CI: 1.23-2.03). Conclusion: Women who were older, current smokers, had higher-grade and ER-negative tumors, and had higher BMI, percent body fat, and waist-to-hip ratio had higher odds of misreporting their BMI. However, overall, self-reported BMI was reasonably accurate among African American breast cancer survivors in this study. Citation Format: Bo Qin, Adana A.M. Llanos, Elizabeth A. Szamreta, Jesse J. Plascak, Christine Ambrosone, Kitaw Demissie, Chi-Chen Hong, Elisa V. Bandera. Validity of self-reported body mass index among African American breast cancer survivors: The Women's Circle of Health Follow-Up Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A57.

Abstract 5328: Intergenic DNA methylation differences in ER- breast tumors from African American versus European American women

Abstract Incidence of estrogen receptor (ER)-negative breast cancer, a subtype with worse prognosis, is higher among African American (AA) versus European American (EA) women. The reasons for this gap remain poorly defined, but likely include differences in the prevalence and biological effects of known risk factors for ER- disease (eg. parity without breastfeeding and early menarche). These exposures may influence risk of ER- cancer via multiple mechanisms, one of which is epigenetic regulation of gene expression. Altered expression of genes controlling the proliferation and/or differentiation of luminal progenitor cells in the breast is likely to affect the propensity of such cells to give rise to ER- versus ER+ cancer. We previously conducted genome-wide DNA methylation profiling of 224 ER- tumor samples from 141 AA and 83 EA women in the Women's Circle of Health Study, and identified 374 differentially methylated loci (DML) by race. Our initial analysis focused on DMLs mapping to annotated genes, and revealed that a key pro-luminal transcription factor gene, FOXA1, was hypermethylated and repressed in AA compared to EA tumors. Moreover, parity without breastfeeding, more common among AAs, was associated with increased FOXA1 methylation. In this study, motivated by the biological importance of the non-coding genome, we focused on ~100 intergenic DML, and used paired 450K and RNA-seq data to assess the relationship between CpG methylation and RNA expression of genes located up to 50 kb away. Methylation at ten DML was significantly correlated with paired gene expression (FDR q<0.05). For seven of these loci, lower methylation tracked with higher expression of the paired gene. One such CpG, hypomethylated in AA versus EA tumors, mapped to a putative enhancer element located 19 kb upstream of, and predicted to interact with, the promoter of LEMD1, a pro-tumorigenic cancer-testis antigen. Analysis of an independent set of 207 ER- breast cancers from TCGA confirmed that LEMD1 RNA expression was higher in AA compared to EA tumors (P=0.01, log2FC=0.95). Our findings suggest that epigenetic differences between AA and EA ER- tumors are linked to altered gene expression and may hold functional significance in breast cancer pathogenesis. Further studies are needed to extend these results to normal breast tissues from cancer-free women, and explore a potential role for FOXA1/LEMD1 epigenetic regulation in luminal progenitor cell homeostasis. Citation Format: Matthew F. Buas, Jianhong Chen, Qiang Hu, Song Liu, Zhihong Gong, Michael J. Higgins, Christine B. Ambrosone. Intergenic DNA methylation differences in ER- breast tumors from African American versus European American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5328.

Abstract 3242: Differences in stromal tumor-infiltrating lymphocytes in breast cancer from women of African and European ancestry after accounting for tumor characteristics

Abstract Background: Women of African ancestry (AA) have higher breast cancer mortality than other US racial/ethnic groups, attributed to a number of social and economic factors. However, breast tumors in AA women are more likely to present with higher grade and lacking estrogen receptor (ER) expression compared to those from women of European ancestry (EA), suggesting the importance of tumor factors in breast cancer disparities. Emerging evidence suggests that stromal tumor-infiltrating lymphocytes (TIL-str) have a role in immune response to therapy and prognosis of breast cancer. The objective of this study was to examine associations between risk factors for breast cancer and TIL-str, with consideration of tumor characteristics. Methods: We reviewed the hematoxylin and eosin slides from surgical or biopsy tumor blocks of invasive breast cancer from 1,385 cases (986 AA and 399 EA women, aged 20-75 years) in the Women's Circle of Health Study, a multicenter case-control study in New York and New Jersey. In-person interviews were conducted at diagnosis to obtain data on demographics, family histories, hormone use, and reproductive and menstrual histories. Anthropometric measurements were taken by trained staff. TIL-str were scored as 0%, 1%, and 10% to 100% in increments of 10%. Linear regressions were performed to estimate differences in TIL-str scores (β). Results: In univariate analysis, TIL-str was higher in tumors from AA than those from EA women overall (mean score = 21.5% vs. 12.5; P<0.001). TIL-str score was positively associated with higher grade, larger tumor size, and ER and progesterone receptor (PR) negativity in both AA and EA women (all P<0.05). In EA women, TIL-str score was also higher in more advanced than early stage tumors and human epidermal factor receptor 2 (HER2) positive than negative tumors (both P<0.05), but not in AA women. In multivariable analysis, AA compared to EA race was significantly associated with a higher TIL-str score (β = 5.7%, P<0.001), adjusting for age at diagnosis, body mass index, menopausal status, tumor grade, size, stage, and molecular subtypes defined by ER, PR, and HER2. There was no apparent association between TIL-str and history of breast cancer in first-degree relatives, history of benign breast disease, hormone use, reproductive factors, or body size. Conclusion: Self-reported African compared to European ancestry is independently associated with higher TIL-str scores in breast tumors. Our findings suggest that immune response may play a role in the differences in breast cancer biology and outcomes between AA and EA women. (Funding: The Breast Cancer Research Foundation; NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334) Citation Format: Ting-Yuan D. Cheng, Rochelle Payne Ondracek, Song Yao, Warren Davis, Angela Omilian, Mateusz Opyrchal, Elisa V. Bandera, Michael J. Higgins, Christine B. Ambrosone, Thaer Khoury. Differences in stromal tumor-infiltrating lymphocytes in breast cancer from women of African and European ancestry after accounting for tumor characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3242.

Validity of self-reported weight, height, and body mass index among African American breast cancer survivors.

Self-reported weight, height, and body mass index (BMI) are commonly used in cancer epidemiology studies, but information on the validity of self-reports among cancer survivors is lacking. This study aimed to evaluate the validity of these self-reported measures among African American (AA) breast cancer survivors, known to have high obesity prevalence. We compared the self-reported and measured values among 243 participants from the Women's Circle of Health Follow-Up Study (WCHFS), a population-based longitudinal study of AA breast cancer survivors. Multivariable-adjusted linear regressions were used to identify factors associated with reporting errors. We also examined the associations of self-reported and measured BMI with obesity-related health outcomes using multivariable logistic regressions, with hypertension as an example, to evaluate the impact of misreporting. We found that self-reported and measured values were highly correlated among all and when stratified by participants' characteristics (intraclass correlation coefficients ≥ 0.99, 0.84, and 0.96 for weight, height, and BMI, respectively). The agreement between BMI categories (normal, overweight and obese) based on self-reported and measured data was excellent (kappa = 0.81). Women who were older, never smoked, had higher grade tumors, or had greater BMI tended to have overestimated BMI calculated from self-reported weight and height. The BMI-hypertension association was similar using self-reported (OR per 5kg/m2 increase 1.63; 95% CI 1.27-2.10) and measured BMI (1.58; 95% CI 1.23-2.03). Self-reported weight, height, and BMI were reasonably accurate in the WCHFS. Our study supports the use of these self-reported values among cancer survivors when direct measurements are not possible.

A Circle of Women: Creating Community for Healing at Four Directions Aboriginal Student Centre

Within the Queen’s University community there are limited culturally appropriate activities for Aboriginal students. Traditionally and currently it is not common practice for an Aboriginal person to go to a stranger for guidance for personal issues. It is more common to seek guidance from a family member, community member or an elder. Aboriginal women in communities across Canada were historically valued as leaders and respected in their various roles within those societies. After colonization Aboriginal peoples were forced to adopt European patriarchal values. Consequently women were no longer allowed to hold leadership positions within their communities and the roles that they did play were perceived as less valuable. In addition to this ideological shift, the spiritual connection that women previously held with each other was disconnected through various processes. The sixties scoop and residential schools were processes that had negatively affected these relationships within Aboriginal societies. The Women’s Circle strives to bridge the disconnect that occurred and utilize time spent together during traditional activities to provide a safe place for this healing to begin. The Women’s Circle will also support Queen’s University’s mandate of engaging diversity and encouraging the Non-Aboriginal community to learn more regarding Aboriginal cultures, as well as the mandate of Four Directions Aboriginal Student Centre, specifically to foster the emotional, mental, physical and spiritual well-being of the Aboriginal Students at Queen’s University.

Genetic variations, reproductive aging, and breast cancer risk in African American and European American women: The Women's Circle of Health Study.

Reproductive aging phenotypes, including age at menarche (AM) and age at natural menopause (ANM), are well-established risk factors for breast cancer. In recent years, many genetic variants have been identified in association with AM and ANM in genome-wide association studies among European populations. Using data from the Women’s Circle of Health Study (WCHS) of 1,307 European-American (EA) and 1,365 African-American (AA) breast cancer cases and controls, we aimed to replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast cancer risk was also examined in relation to a polygenic risk score (PRS) for each of the reproductive aging phenotypes. We replicated a number of variants in EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM; whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was directionally consistent and nominally significant. In analysis of TRLS and NRLS, several SNPs were significant, including rs466639 in RXRG that was associated with both phenotypes in both AA and EA groups. None of the PRS was associated with breast cancer risk. Given the paucity of data available among AA populations, our study contributes to the literature of genetics of reproductive aging in AA women and highlights the importance of cross population replication of GWAS variants.

Demographic, lifestyle, and genetic determinants of circulating concentrations of 25-hydroxyvitamin D and vitamin D–binding protein in African American and European American women ,

Background: Vitamin D may have anticancer activities. The high prevalence of vitamin D deficiency in African Americans (AAs) may be a contributing factor to the cancer health disparities between AAs and European Americans (EAs).Objectives: We compared concentrations of 25(OH)D and vitamin D-binding protein (VDBP) in AA and EA women and investigated determinants of the vitamin D-biomarker concentrations in both populations.Design: We used data and biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS) in the African American Breast Cancer Epidemiology and Risk Consortium. We measured plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67 vitamin D-related genes in AA women only.Results: AA women had lower 25(OH)D concentrations than did EA women (mean ± SD: 14.2 ± 8.1 compared with 21.1 ± 11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean ± SD: 344 ± 133 compared with 336 ± 124 μg/mL, respectively; P = 0.25). With VDBP and other factors controlled for, the observed racial difference in 25(OH)D concentrations did not diminish. Relations of demographic and lifestyle factors with 25(OH)D were similar between AA and EA women. Although none of the genetic variants that have been identified in previous genome-wide association studies of 25(OH)D concentrations in EAs were significant (P > 0.05) in AAs, AA women who carried the allele of a functional single nucleotide polymorphism rs4988235, which has been previously associated with lactase expression and lactose tolerance, had higher dietary vitamin D intake and higher measured 25(OH)D concentrations.Conclusions: AA women have lower concentrations of total 25(OH)D than EA women do, but both groups have similar VDBP concentrations, suggesting that there are lower concentrations of free 25(OH)D in AAs. Although demographic and lifestyle determinants of 25(OH)D concentrations are similar between the 2 groups, genetic determinants may be ethnicity specific. Larger studies in AAs will be needed to fully elucidate the underlying determinants of low vitamin D concentrations in AA populations.

Abstract B81: Hair product use and breast cancer risk by hormone receptor status in the Women's Circle of Health Study

Abstract Introduction: Over the last several decades, the concern of environmental exposures to certain carcinogens and mutagens found in hair products, particularly hair dyes, have been explored for evidence of an association with breast cancer risk, yielding equivocal results. However, little is known about this association among African American (AA) women, who are common users of these products. The objective of this study was to examine the prevalence and patterns of use of hair products in AA and European American (EA) women in the Women's Circle of Health Study (WCHS), and their associations with breast cancer risk, overall and by estrogen receptor (ER+, ER-) and triple negative (TN) status. Methods: Data collection for the WCHS, a case-control study of breast cancer in New York City and several counties in New Jersey, was conducted through in-person interviews, with anthropometric and body composition measurements taken, and review of pathology records. At study entry, participants were asked on use of hair dyes, chemical relaxers/straighteners and cholesterol- and/or placenta-containing conditioning creams. Chi-square tests were used to compare differences in hair product variables by case-control status among AAs and EAs. Race-stratified, age-adjusted and multivariable-adjusted unconditional logistic regression models controlling for age, race, education, family history of breast cancer, oral contraceptive use, and body mass index were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between hair product use and risk among 4,285 women with breast cancer and controls (AA, n=2,798 and EA, n=1,487). Results: Among controls, 30.23% of AAs and 57.76% of EAs regularly used hair dye. Compared to light hair dye shades (blonde, light brown) use of darker shades (dark brown, black) was associated with increased odds of breast cancer among AA women (OR 1.64, 95% CI: 1.19-2.27), although there did not appear to be a dose response association with frequency of use. There were no associations between hair dye use and breast cancer risk among EA women. Use of chemical relaxers was more common among AAs than EAs (87.13% vs. 4.62% of AA and EA controls, respectively). Compared to AA women who used chemical relaxers without lye, those using products with lye were at increased risk (OR 1.54, 95% CI: 1.22-1.94). Among EA women although use of relaxers was not very common, compared to never users, those using relaxers (OR 1.74, 95% CI: 1.11-2.74) and using lye-containing relaxers (OR 4.37, 95% CI: 1.65-11.88) were at increased risk. Regular hair dye use (OR 1.20, 95% CI: 1.03-1.39), use of darker hair dye shades (OR 1.37, 95% CI: 1.05-1.77), and use of relaxers that contain lye (OR 1.26, 95% CI: 1.03-1.55) were associated with increased risk of ER+ BC. Regularly using both hair dyes and relaxers was associated with increased risk of ER+ BC (OR 1.20, 95% CI: 1.00-1.44). Regular hair dye use was not associated with risk of ER- or TNBC. The use of deep conditioning creams that contain cholesterol or placenta was also more common among AAs than EAs (56.12% vs. 6.01% of controls, respectively). However, there were no associations between use of these products and breast cancer risk. Conclusions: These findings from a large case-control study of AA and EA women provide additional epidemiological data to support a relationship between the use of some hair products, namely hair dyes and chemical relaxers, and risk of breast cancer. As use of various hair products and other cosmetics continue to increase among women in the U.S., particularly those at increased risk of breast cancer, improved awareness of the potential effects of exposures to their chemical ingredients are needed. Citation Format: Adana A.M. Llanos, Anna Rabkin, Gary Zirpoli, Cathleen Y. Xing, Bo Qin, Brian D. Gonzalez, Chi-Chen Hong, Kitaw Demissie, Elisa V. Bandera, Christine B. Ambrosone. Hair product use and breast cancer risk by hormone receptor status in the Women's Circle of Health Study. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B81.

Genetic variation in the insulin, insulin-like growth factor, growth hormone, and leptin pathways in relation to breast cancer in African-American women: the AMBER consortium.

The insulin/insulin-like growth factor (IGF) system and related pathways such as growth hormone, and leptin signaling have a key role in cancer development. It is unclear how germline variation in these pathways affects breast cancer risk. We conducted gene-based analyses of 184 genes in the insulin/IGF, growth hormone, and leptin pathways to identify genetic variation associated with risk of breast cancer overall, and for estrogen receptor (ER) subtypes. Tag single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina SNP array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs genotyped or imputed in 3,663 breast cancer cases, (1,983 ER-positive and 1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African-American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint test to determine the association of each gene with overall breast cancer and ER subtypes. The most significant gene associations (P⩽0.01) were BAIAP2 and CALM2 for overall breast cancer; BAIAP2 and CSNK2A1 for ER+ breast cancer; and BRAF, BAD, and MAPK3 for ER− breast cancer. The association of BAD with ER− breast cancer was explained by a two-SNP risk model; all other associations were best explained by one-SNP risk models. In total, six genes and seven SNPs had suggestive associations with overall breast cancer or ER subtypes in African-American women.

Single nucleotide variants in metastasis-related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry.

Single nucleotide polymorphisms (SNPs) in pathways influencing lymph node (LN) metastasis and estrogen receptor (ER) status in breast cancer may partially explain inter-patient variability in prognosis. We examined 154 SNPs in 12 metastasis-related genes for associations with breast cancer risk, stratified by LN and ER status, in European-American (EA) and African-American (AA) women. Two-thousand six hundred and seventy-one women enrolled in the Women's Circle of Health Study were genotyped. Pathway analyses were conducted using the adaptive rank truncated product (ARTP) method, with pARTP ≤ 0.10 as significant. Multi-allelic risk scores were created for the ARTP-significant gene(s). Single-SNP and risk score associations were modeled using logistic regression, with false discovery rate (FDR) P-value adjustment. Although single-SNP associations were not significant at pFDR < 0.05, several genes were significant in the ARTP analyses. In AA women, significant ARTP gene-level associations included CDH1 with LN+ (pARTP = 0.10; multi-allelic OR = 1.13, 95%CI 1.07-1.19, pFDR = 0.0003) and SIPA1 with ER- breast cancer (pARTP = 0.10; multi-allelic OR = 1.16, 95%CI 1.02-1.31, pFDR = 0.03). In EA women, MTA2 was associated with overall breast cancer risk (pARTP = 0.004), regardless of ER status, and with LN- disease (pARTP = 0.01). Also significant were SATB1 in ER- (pARTP = 0.03; multi-allelic OR = 1.12, 95%CI 1.05-1.20, pFDR = 0.003) and KISS1 in LN- (pARTP = 0.10; multi-allelic OR = 1.18, 95%CI 1.08-1.29, pFDR = 0.002) analyses. Among LN+ cases, significant ARTP associations were observed for SNAI1, CD82, NME1, and CTNNB1 (multi-allelic OR = 1.09, 95%CI 1.04-1.14, pFDR = 0.001). Our findings suggest that variants in several metastasis genes may affect breast cancer risk by LN or ER status, although verification in larger studies is required. © 2016 Wiley Periodicals, Inc.

Abstract 814: Gene-based analysis of the IGF signaling pathway and risk of breast cancer in African American women: The AMBER consortium

Abstract Dysregulation of the IGF (insulin-like growth factor) signaling pathway plays a key role in cancer development. It is still unclear whether germline variation in genes in the IGF pathway may affect risk of breast cancer. We conducted a gene-based analysis of 184 genes in the IGF signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 91,627 SNPs in 3,663 breast cancer cases (including 1,983 ER positive,1,098 ER-negative) and 4,687 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the IGF signaling pathway with overall breast cancer and ER subtypes. None of the 184 tested genes, including IGF, IGF binding protein (IGFBP), and IGF receptor (IGFR) genes were associated with disease after adjustment for multiple testing. At the nominal level of P≤0.01, BAIAP2 (P = 0.003), and CALM2 (P = 0.009) genes were associated with overall breast cancer; BAIAP2 (P = 0.001), and CSNK2A1 (P = 0.01) with ER+ breast cancer; and BRAF (P = 0.003), BAD (P = 0.005), and MAPK3 (P = 0.009) with ER- breast cancer. The intronic rs9913477 SNP in the BAIPA2 gene was significantly associated with overall (P = 3.2×10−7) and ER+ (P = 4.4×10−7) breast cancer at the pathway-wide level after adjusting for the total number of tested SNPs. Odds ratios and 95% confidence intervals of the risk G-allele were 1.44 (1.25, 1.66), and 1.53 (1.30, 1.81) for overall and ER+ breast cancer, respectively. BAIAP2 codes an adaptor protein, IRSp53, which functions as a substrate of the insulin receptor and IGF-1 receptor tyrosine kinases and links Rho-family small GTPases such as Rac. In vitro studies have shown that activation of Rac promotes metastatic behavior of breast cancer cells. In conclusion, we identified a SNP in BAIAP2 associated with overall and ER+ breast cancer. These results highlight the importance of the IGF signaling pathway in the pathogenesis of breast cancer. Citation Format: Edward A. Ruiz-Narvaez, Kathryn L. Lunetta, Chi-Chen Hong, Stephen A. Haddad, Song Yao, Ting-Yuan D. Cheng, Jeannette T. Bensen, Elisa V. Bandera, Christopher A. Haiman, Andrew F. Olshan, Christine B. Ambrosone, Lynn Rosenberg, Julie R. Palmer. Gene-based analysis of the IGF signaling pathway and risk of breast cancer in African American women: The AMBER consortium. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 814.

Abstract B47: Methylation differences in breast tumor DNA from African American and European women are predominant in estrogen receptor (ER) negative breast cancer and are associated with childbearing

Abstract Background: Although European American (EA) women have higher incidence of breast cancer than African American (AA) women, AA women are more often diagnosed with aggressive estrogen receptor negative (ER-) tumors, the risk of which increases with parity, lack of breastfeeding, and an early age at menarche. DNA methylation could be affected by reproductive factors and may be a potential molecular mechanism driving differences in tumor etiology. In a small study using fresh frozen breast tissue (n=58 AA, 80 EA), we previously found more differentially methylated loci (DMLs) in ER- tumors from AA and EA women than in ER+ tumors. Methods: To follow up on these preliminary findings, we used the Illumina 450K platform to determine genome-wide DNA methylation profiles in formalin fixed paraffin embedded (FFPE) breast tumors from 383 AA and 350 EA women who participated in the Women's Circle of Health Study, a case control study conducted in NY and NJ. We identified DMLs by race and ER status, as well as differentially methylated regions (DMRs). DMLs in eight genes were validated using the Sequenom EpiTYPER platform. Recursively partitioned mixture modeling (RPMM) package in R was used to examine relationships between methylation clusters and reproductive factors, information available from in-person interviews. In addition, using fresh frozen tumor tissue from 50 patients treated at Roswell Park Cancer Institute, we performed RNA sequencing on samples with methylation data available from a prior study, and used Spearmen's correlation to compare methylation and gene expression of DMLs and DMRs. Results: In assessing average methylation by location relative to CpG-islands (CGIs), we found that CGIs and shores in ER- tumors were significantly hypomethylated compared to CGI and shores in ER+ tumors from AA women, but not in tumors from EA women. We also identified 410 DMLs (Δβ&amp;gt;0.10 &amp; FDR&amp;lt;0.05) between AA and EA breast tumors (race-associated DMLs, raDMLs), the majority of which were unique to ER- tumors (n = 260) and hypomethylated in AAs. These loci were enriched for immune response genes and several cell adhesion and inflammatory pathways. RPMM showed that parity, but not breastfeeding or age at menarche, was significantly associated with methylation class of ER- breast tumors. Of the genes that had ER- specific raDMLs, FOXA1 and THSD4 DNA methylation was highly correlated with gene expression (rho=-0.80, rho=+0.87, respectively; pvalue&amp;lt; 2.2x10-16). Summary: ER- tumors from AA women, but not from EA women, exhibited global hypomethylation at CGI and shores compared to ER+ tumors and contained the majority of raDMLs, many of which were associated with genes involved in immune and inflammatory response. The FOXA1 gene, which encodes a pioneer factor previously implicated in suppressing the molecular phenotype of basal breast cancer cells, was found to be methylated and silenced in the majority of ER- tumors analyzed for expression, consistent with aggressiveness of these tumors. These results, and the novel finding of associations between parity and DNA methylation signature, bring us a step forward in understanding the heterogeneous population of ER- tumors and provide insight into mechanisms of racial disparities in breast cancer. Citation Format: Allyson C. Espinal, Dan Wang, Lara Sucheston-Campbell, Song Liu, Qiang Hu, Li Tang, Gary Zirpoli, Thaer Khoury, Song Yao, Kitaw Demissie, Elisa V. Bandera, Christine B. Ambrosone, Michael J. Higgins. Methylation differences in breast tumor DNA from African American and European women are predominant in estrogen receptor (ER) negative breast cancer and are associated with childbearing. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B47.

Abstract B53: Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium

Abstract Background: African Americans (AAs) are known to have a higher prevalence of vitamin D deficiency than European Americans (EAs). Aside from darker skin pigmentation being a major contributing factor, few studies have investigated determinants of blood levels of 25-hydroxyvitamin D (25OHD) in AA women. Recent evidence suggests that differences in levels between AAs and EAs were largely eliminated after accounting for levels of vitamin D binding protein (VDBP). In the current study, we conducted a comprehensive investigation of associations between genetic and non-genetic factors, including circulating VDBP levels, and serum 25OHD levels in AA and EA women. Study population and methods. Data and biospecimens were examined in the context of the African American Breast Cancer Risk and Epidemiology (AMBER) consortium. For this analysis, levels were measured in 1,756 healthy controls from two case-control studies in AMBER, the Carolina Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS), and included 909 AA and 847 EA women. Blood samples collected at the time of enrollment were used for 25OHD measurement by DiaSorin Liasion immunochemiluminometric assay and VDBP measurement by Assaypro Gc-Globulin ELISA assays. Epidemiological data were collected from questionnaires and harmonized across studies. Genotype data for 25,248 typed and imputed germline variants in vitamin D-related pathways were available as a part of exome genotyping array from AAs in the consortium. Percent of European ancestry in AAs was estimated based on genotype data of ancestry informative markers. Univariate analyses and generalized linear regression analyses were conducted to relate serum 25OHD levels with genetic and non-genetic factors and between AA and EA women. Results: AA women had markedly lower 25OHD levels than EA women (14.2 ng/ml vs. 21.1 ng/ml, p&amp;lt;0.0001), yet had similar levels of VDBP (344 ug/ml vs. 336 ug/ml, p=0.25), which is different from the previous study in AAs showing much lower VDBP levels in AAs than in EAs. Also different is that VDBP levels with were not affected by the two GC polymorphisms rs4588 and rs7041. In AAs, a higher percent of European ancestry was also associated with higher 25OHD levels (p=0.03). Race was the strongest determinant of 25OHD levels, followed by body mass index (BMI), physical activity (walking for exercise), season of blood collection, multivitamin use, dietary vitamin D intake, cigarette smoking and study. Accounting for VDBP levels had little impact on racial difference in 25OHD levels. In analysis of germline variants with serum 25OHD levels, none of the index genome-wide association study (GWAS) variants identified in EAs, including rs2282679 and rs7041 in GC, were significant in AAs in our study. Conclusion: VDBP levels had little impact on notable differences in blood 25OHD levels between AAs and EAs. In addition to race, obesity, season of assessment, and several lifestyle factors were also important determinants of 25OHD levels. Genetic determinants of 25OHD levels in AAs are likely different from those in EAs, which warrants further investigation. Citation Format: Song Yao, Chi-Chen Hong, Ting-Yuan David Cheng, Gary Zirpoli, Stephen A. Haddad, Katherine L. Lunetta, Elisa V. Bandera, Andrew F. Olshan, Julie R. Palmer, Christine B. Ambrosone. Determinants of serum 25-hydroxyvitamin D levels in African American women in the AMBER Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B53.

Abstract C49: Relation of family history of cancer to risk of ER+, ER-, and triple-negative breast cancer in African American women

Abstract Introduction: Family history of breast cancer has been shown to be a strong risk factor for breast cancer in all populations studied. However, there are limited data related to risk of estrogen receptor negative (ER-) breast cancer in African American women, who have a disproportionately high incidence of ER- and triple negative (ER-, progesterone receptor negative, and HER2 receptor negative; TN) breast cancer. Even less information is available on whether a family history of other cancers also affects risk of ER- and TN breast cancer. Methods: Questionnaire data from the Black Women's Health Study, the Carolina Breast Cancer Study, the Multiethnic Cohort Study, and the Women's Circle of Health Study were pooled as part of the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. Breast cancer cases were classified as ER+, ER-, and TN based on pathology data from medical records and/or state cancer registries. Participants were asked about first degree relatives with a breast cancer diagnosis and the age at which the relative was diagnosed. Participants were also asked about first degree relatives with prostate, lung, colorectal, ovarian, or cervical cancer or with lymphoma or leukemia. Polytomous logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for various categories of positive family history relative to no first degree relative with breast cancer or no first degree relative with any of the cancers. Multivariable analyses controlled for age, study, time period, and other potential confounders. Results: The analysis included 3,023 African American women with ER+, 1,497 with ER-, and 696 with TN breast cancer and 17,420 controls. First degree family history of breast cancer, regardless of whether first degree relatives had cancers other than breast cancer, was associated with a 70% increased risk of ER+, ER- and TN breast cancer; the ORs were 1.7 (95% CI 1.6-2.0) for ER+, 1.7 (95% CI 1.4-1.9) for ER-, and 1.7 (95% CI 1.4-2.1) for TN breast cancer. The ORs were somewhat higher if the relative was diagnosed before age 50 (2.0 for ER+, 1.9 for ER-, and 1.8 for TN). Among the six other cancer sites examined, only family history of cervical cancer was significantly associated with risk; the ORs were 2.4 (1.4-4.2) for ER- and 2.9 (1.5-5.5) for TN breast cancer and there was no association with ER+ breast cancer. The OR for family history of ovarian cancer in relation to TN breast cancer was 1.6 (0.9-2.7), which is of interest because findings from The Cancer Genome Atlas (TCGA) indicate that serous ovarian cancers and basal-like breast cancers, which are mostly triple negative, have many molecular commonalities. The ORs for a family history of both breast and prostate cancer versus no family history of any of the cancers were 3.4 (2.4-4.7) for ER+ cancer, as compared with 1.6 for breast alone (p-interaction=0.01), and 2.1 (1.2-3.7) for ER- cancer, as compared with 1.5 for breast alone (p-interaction=0.08). The OR for a family history of both breast and lung cancer was 3.3 (1.9-5.9) for TN breast cancer, compared to 1.5 for breast alone (p-interaction=0.10). The ORs for family history of breast plus two other cancers were 2.4 (1.6-3.6) for ER+, 2.8 (1.6-4.7) for ER-, and 2.7 (1.3-5.7) for TN breast cancer. Conclusion: Our results confirm that having a first degree family history of breast cancer is a strong risk factor for ER+, ER-, and TN breast cancer. The findings also suggest that having relatives with other cancers in addition to a relative with breast cancer may further increase risk. Consideration of family history of other cancers may improve risk prediction models. The association observed for family history of cervical cancer and increased risk of ER- and TN breast cancer was unexpected and needs to be replicated by other studies. Citation Format: Traci N. Bethea, Lynn Rosenberg, Nelsy Castro-Webb, Kathryn L. Lunetta, Lara E. Sucheston, Edward A. Ruiz-Narvaez, Marjory Charlot, Song Y. Park, Elisa V. Bandera, Melissa A. Troester, Christine B. Ambrosone, Julie R. Palmer. Relation of family history of cancer to risk of ER+, ER-, and triple-negative breast cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C49.

Abstract A77: Walking and vigorous exercise and risk of breast cancer in African American women

Abstract The relationship between physical activity and breast cancer risk has been extensively studied among women of European descent, with most studies reporting an inverse association. However, data on African American (AA) women and by tumor subtypes are sparse. Thus, we examined associations of vigorous exercise and walking for exercise and breast cancer risk overall and by estrogen receptor (ER) status in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium. We pooled data on AA women from four large studies, the Black Women's Health Study, Carolina Breast Cancer Study, Multiethnic Cohort Study and Women's Circle of Health Study, for 2,482 ER+ cases, 1,374 ER- cases and 16,959 controls. Multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) for the risk of overall breast cancer, and polytomous logistic regression was used to model the risk of ER+ and ER- cancer. Based on all four studies, for recent vigorous exercise (reported by 29% of controls), the OR was 0.88 (95% CI: 0.81-0.96) for breast cancer overall, 0.88 (95% CI: 0.80-0.98) for ER+ breast cancer and 0.93 (95% CI: 0.82-1.06) for ER- breast cancer. There was a statistically significant trend across hours per week of vigorous activity for breast cancer overall (p for trend=0.006) and for ER+ cancer (p for trend=0.02), but there was not a clear dose response relationship, with the strongest reduced risk in the 1-2 and 3-4 hours/week categories. Data on walking for exercise, as the most frequently reported activity among adults who meet guidelines for regular physical activity (53% in controls), was available from two studies. Any walking for exercise was associated with reduced risk of breast cancer overall (OR=0.88, 95% CI: 0.80-0.97) and ER+ cancer (OR=0.87, 95% CI: 0.77-0.98), but not ER- cancer (OR=0.95, 95 CI: 0.81-1.12). There was a significant trend across hours per week of walking for breast cancer overall (p for trend=0.008) and ER+ breast cancer (p for trend=0.02), with the strongest reduced risk in the 5+ hours/week category. Our results from this large pooling study of AA women provide evidence that vigorous exercise and walking for exercise are associated with reduced risk of breast cancer, specifically ER+ cancer. Citation Format: zhihong Gong, Chi-Chen Hong, Elisa Bandera, Lucile Adams-Campbell, Song-Yi Park, Gary Zirpoli, Andrew Olshan, Christine Ambrosone, Julie Palmer, Lynn Rosenberg. Walking and vigorous exercise and risk of breast cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A77.

Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium.

We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3237 SNPs in 3663 breast cancer cases (including 1983 ER-positive, and 1098 ER-negative) and 4687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. The FGF1 gene was significantly associated with risk of ER-negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER-positive breast cancer (P = 0.002). The FGF1 gene affects risk of ER-negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER-positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes.