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supplemental Tables 1-5. Supplemental Table 1: Characteristics of Study Population. Supplemental Table 2: Body Size Characteristics among Postmenopausal Controls, by Ethnicity and Genetic Admixture among Hispanics. Supplemental Table 3: Abdominal Adiposity Associations with Breast Cancer Risk in Hispanic Postmenopausal Women Measured

Association between ten GWAS-identified SNPs and breast cancer risk, stratified by environmental risk factors, in Hispanic women from the Breast Cancer Health Disparities Study

Background: Few studies in Hispanic women have examined the relation between adult body size and risk of premenopausal breast cancer defined by hormone receptor status.Methods: The Breast Cancer Health Disparities Study pooled interview and anthropometric data from two large U.S. population-based case–control studies. We examined associations of overall and abdominal adiposity with risk of estrogen receptor– and progesterone receptor–positive (ER+PR+) and –negative (ER−PR−) breast cancer in Hispanic and non-Hispanic White (NHW) women, calculating ORs and 95% confidence intervals.Results: Among Hispanics, risk of ER+PR+ breast cancer was inversely associated with measures of overall adiposity, including young-adult and current body mass index (BMI). Risk was substantially reduced among those with high (above the median) young-adult BMI and current overweight or obesity. The findings for overall adiposity were similar for Hispanics and NHWs. In the subset of Hispanics with data on genetic ancestry, inverse associations of current BMI, and weight gain with ER+PR+ breast cancer were limited to those with lower Indigenous American ancestry. For ER−PR− breast cancer, height was associated with increased risk, and young-adult BMI was associated with reduced risk. For all breast cancers combined, positive associations were seen for waist circumference, waist-to-hip ratio, and waist-to-height ratio in Hispanic women only.Conclusions: Our findings of body size associations with specific breast cancer subtypes among premenopausal Hispanic women were similar to those reported for NHW women.Impact: Adiposity throughout the premenopausal years has a major influence on breast cancer risk in Hispanic women. Cancer Epidemiol Biomarkers Prev; 24(1); 138–47. ©2014 AACR.See related article by John et al., p. 128

Background: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene–environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population.Methods: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions.Results: We found that the rs13387042–2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74–1.20), 1.20 (0.94–1.53), and 1.49 (1.28–1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72–1.42), 1.19 (0.98–1.45), and 1.69 (1.26–2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014].Conclusions: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women.Impact: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1731–8. ©2015 AACR.

Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown.Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study.Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00–1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29–2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI 30: OR = 0.65 (95% CI, 0.44–0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29–0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry.Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry.Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692–701. ©2016 AACR.

Background: Few studies have assessed the association of body size with postmenopausal breast cancer risk in Hispanic women. Findings are inconsistent and appear to contradict those reported for non-Hispanic white (NHW) women.Methods: We pooled interview and anthropometric data for 2,023 Hispanic and 2,384 NHW women from two U.S. population-based case–control studies. Using logistic regression analysis, we examined associations of overall and abdominal adiposity with risk of postmenopausal breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status.Results: Weight gain was associated with increased risk of ER+PR+ breast cancer in Hispanics not currently using menopausal hormone therapy (HT), but only among those with a low young-adult body mass index (BMI). In the subset of Hispanics with data on genetic ancestry, the association with weight gain was limited to women with lower Indigenous American ancestry. Young-adult BMI was inversely associated with both ER+PR+ and ER−PR− breast cancers for both ethnicities combined, with similar, although nonsignificant, inverse trends in Hispanics and NHWs. Among all Hispanics, regardless of HT use, height was associated with risk of ER−PR− breast cancer and hip circumference with risk of breast cancer overall.Conclusions: Body size throughout adult life is associated with breast cancer risk among postmenopausal Hispanic women, as has been reported for NHW women. Associations were specific for breast cancer subtypes defined by hormone receptor status.Impact: Avoiding weight gain and maintaining a healthy weight are important strategies to reduce the risk of postmenopausal ER+PR+ breast cancer, the most common breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 24(1); 128–37. ©2014 AACR.See related article by John et al., p. 138

Supplemental Table 1. Relationship between percent Native American ancestry and ER positive breast cancer among postmenopausal non-Hispanic Whites and US Hispanics. Supplemental Table 2. Relationship between percent Native American ancestry and ER negative breast cancer among postmenopausal non-Hispanic Whites and US Hispanics. Supplemental Table 3. Relationship between risk factors and ER positive breast cancer among postmenopausal non-Hispanic Whites and US Hispanics according to percent Native American ancestry. Supplemental Table 4. Relationship between risk factors and ER negative breast cancer among postmenopausal non-Hispanic Whites and US Hispanics according to percent Native American ancestry.

Supplemental Tables 1-3. Supplemental Table 1: Characteristics of Study Population. Supplemental Table 2: Body Size Characteristics among Premenopausal Controls, by Ethnicity and Genetic Admixture among Hispanics. Supplemental Table 3: Height and Overall Adiposity Associations with ER+PR+ Breast Cancer in Premenopausal Hispanic Women, by Genetic Ancestry

PURPOSE: To explore the relationship between physical activity (PA) and quality of life (QOL) among Hispanic and non-Hispanic white breast cancer (BC) cases and population-based controls from the New Mexico ‘Long-Term Quality of Life Study’. METHODS: Self-reported PA (low, moderate, vigorous MET hours/week) at baseline and follow-up interviews (12–15 years) were available for 391 cases and controls and modeled using multiple linear regressions with SF-36 mean composite scores for physical and mental health. The change in PA from baseline to follow-up and interactions with ethnicity were also examined. Models were adjusted for age at diagnosis/baseline interview, education, comorbidities, body mass index, and change in PA. RESULTS: PA intensities at each timepoint did not differ by case/control status; however, the change in vigorous PA was lower among cases (p = 0.03). At follow-up, low intensity PA increased mental health QOL scores among cases; however, the interaction between low intensity PA and ethnicity was statistically significant among controls indicating decreased mental health among Hispanics (p = 0.02). Change in moderate PA was associated with increased physical and mental health among cases (physical: β = 0.186, p = 0.008; mental: β = 0.225, p = 0.001) and controls (physical: β = 0.220, p < 0.0001; mental: β = 0.193, p = 0.002), when controlling for confounders. CONCLUSION: Our results demonstrate that all levels of PA are important for mental health among BC cases, while activities of higher intensity are important for physical health among women overall. The statistical interaction observed between ethnicity and low intensity PA among controls for mental health warrants further research to provide a meaningful interpretation.

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35–64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values

Physical activity is recommended for most cancer patients as a nonpharmacological therapy to improve prognosis. Few studies have investigated the association between physical activity and breast cancer prognosis by ethnicity, biological, and modifiable risk factors for mortality. We investigated the association between physical activity and long-term survival among breast cancer survivors. A total of 397 survivors (96 Hispanic and 301 non-Hispanic White (NHW)) from the New Mexico HEAL study contributed baseline and biological data approximately 6 months after diagnosis. Study outcomes included all-cause, breast cancer-specific, and non-breast cancer mortality. The exposure was self-reported physical activity within the past month. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox Proportional Hazards regression. A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. Engaging in >6.9 metabolic equivalent hours/week (MET-h/week) of moderate to vigorous physical activity (active) was inversely associated with all-cause mortality among all women (HR 0.66, 95% CI 0.43–0.99) and NHWs (HR 0.58, 95% CI 0.36–0.94). Active NHW women also had a reduced risk of non-breast cancer mortality (HR 0.56, 95% CI 0.31–0.99), compared to inactive women (0 MET-h/week). In subgroups, we observed the inverse associations with all-cause mortality among women >58 years old (p-interaction= 0.03) and with localized stage (p-interaction = 0.046). Our results confirm the protective association between physical activity and mortality after breast cancer diagnosis, and demonstrate that this association significantly differs by age and cancer stage. Larger studies are warranted to substantiate our findings.

We pooled multiethnic data from four population-based studies and examined associations of menstrual and reproductive characteristics with breast cancer (BC) risk by tumor hormone receptor (HR) status [defined by estrogen receptor (ER) and progesterone receptor (PR)]. We estimated odds ratios and 95% confidence intervals using multivariable logistic regression, stratified by age (

Reproductive and hormonal factors may influence breast cancer risk via endogenous estrogen exposure. Cumulative menstrual months (CMM) can be used as a surrogate measure of this exposure. Using harmonized data from four population-based breast cancer studies (7,284 cases and 7,242 controls), we examined ethnicity-specific associations between CMM and breast cancer risk using logistic regression, adjusting for menopausal status and other risk factors. Higher CMM was associated with increased breast cancer risk in non-Hispanic Whites, Hispanics and Asian Americans regardless of menopausal status (all FDR adjusted p trends=0.0004), but not in African Americans. In premenopausal African Americans, there was a suggestive trend of lower risk with higher CMM. Stratification by body mass index (BMI) among premenopausal African American women showed a nonsignificant positive association with CMM in non-obese (BMI

Epidemiologic studies have found that elevated insulin levels and chronic hyperglycemia among breast cancer (BC) survivors are associated with poor prognosis; few of these studies have included Hispanic women in whom diabetes is highly prevalent. We examined the associations between circulating fructosamine-a biomarker of hyperglycemia and blood glucose control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with invasive BC. A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. After a median follow-up time of 13 years, a total of 134 deaths occurred, of which 56 deaths were from BC. Diabetes was associated with BC-specific (HR, 2.89; 95% CI 1.27–6.60) and all-cause (HR, 2.10; 95% CI 1.24–3.55) mortality. Associations were stronger among women with clinically high fructosamine levels (>285 µmol/L) (BC-specific: HR, 4.25; 95% CI 1.67–10.80; all-cause: HR, 2.32; 95% CI 1.30–4.14) compared to women with normal levels (≤285 µmol/L). In mediation analysis, fructosamine explained 47% of the association between diabetes and all-cause mortality and 41% of BC-specific mortality; the largest attenuation was among Hispanics for all-cause mortality (56%). Our results demonstrate that poor glycemic control explains a large extent of the relationship between diabetes and mortality among women with invasive BC, particularly among Hispanic women. The associations we observed for BC mortality should be confirmed in larger studies of ethnically diverse BC patients., Epidemiology: Poor glycemic control increases risk of cancer-linked death Diabetes and poor blood sugar control significantly increase a woman’s odds of dying from invasive breast cancer. A team led by Avonne Connor from Johns Hopkins University in Baltimore, Maryland, USA, tracked the fate of 399 survivors of breast cancer, 96 of whom were Hispanic, an underrepresented ethnicity in many biomedical studies. After a median follow-up of 13 years, the researchers found that women with diabetes had a nearly 3-fold higher risk of dying from their breast cancer and more than a two-fold greater risk for all-cause mortality. Poor glycemic control, as measured by elevated levels of a common blood biomarker called fructosamine, explained a large extent of the relationship between diabetes and cancer-linked mortality, especially among Hispanic women. The findings suggest that better glucose management could improve outcomes for breast cancer survivors with diabetes.

INTRODUCTION: Soluble tumor necrosis factor receptor-II (sTNF-R2), a pro-inflammatory biomarker, is associated with obesity and breast cancer (BC). The association between sTNF-R2 and risk of mortality after BC has not been studied, specifically among Hispanic women, an at-risk population due to their high prevalence of obesity and poor prognosis. We examined the association between sTNF-R2 and mortality among Hispanic and non-Hispanic white (NHW) BC survivors. METHODS: A total of 397 invasive BC survivors (96 Hispanic, 301 NHW) contributed baseline interview data and blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models adjusting for clinical factors including body mass index. RESULTS: After a median follow-up time of 13 years, 133 deaths occurred. The association between high vs low levels of plasma sTNF-R2 and mortality was not statistically significant overall (HR, 1.32; 95% CI 0.89–1.98). However, when stratified the mortality risk among Hispanic women was nearly 3-fold (HR, 2.83; 95% CI 1.21–6.63), while risk among NHW women was attenuated (HR, 0.99; 95% CI 0.61–1.61) (p-interaction=0.10). CONCLUSION: Our results suggest Hispanic BC survivors with high sTNF-R2 levels may have increased risk of mortality and could inform targeted interventions to reduce inflammation and improve outcomes.

Background: Evidence suggests that the presence of Type-2 diabetes at the time of breast cancer diagnosis adversely affects survival independent of breast cancer stage, grade, and tumor phenotype. Few of these epidemiological studies have included Hispanic breast cancer survivors in whom diabetes and obesity are prevalent. Objective: We examined the association between self-reported diabetes history, breast cancer-specific and all-cause mortality among Hispanic and non-Hispanic white (NHW) women diagnosed with breast cancer (stages I-IIIa) from the New Mexico Health, Eating, Activity, and Lifestyle cohort. Methods: A total of 399 breast cancer survivors (96 Hispanic, 303 NHW) contributed data for the present study. Women with breast cancer diagnosed between July 1996 and March 1999 were ascertained through the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry in New Mexico. Baseline demographic characteristics and breast cancer risk factors were collected approximately 5 months post diagnosis by trained interviewers. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. Models were further stratified by ethnicity. Results: After a median follow-up time of 13.5 years from baseline interview to death, a total of 134 deaths occurred. The prevalence of diabetes did not significantly differ by ethnicity in our study; 11.5% of Hispanics reported having diabetes compared to 7.5% of NHW women. While a history of diabetes was associated with older age at breast cancer diagnosis (p=0.001), higher percent body fat (p=0.01), higher body mass index (p< 0.001), and increased waist-hip ratio (p< 0.001) compared to non-diabetics, no significant differences were observed between diabetics and non-diabetics for breast cancer stage, grade, tumor phenotype, or receipt of breast cancer treatment. In multivariable models, diabetes was associated with increased risk of all-cause mortality overall (HR, 2.10; 95% CI 1.24-3.55), with a significant association only observed among Hispanic women (HR, 3.07; 95% CI 1.05-8.94) when compared to NHW women (HR, 1.66; 95% CI 0.86-3.24). The interaction between ethnicity and diabetes was not statistically significant for all-cause mortality. Diabetes also was significantly associated with increased risk of breast cancer-specific mortality (HR, 2.89; 95% CI 1.27-6.60); however results were not statistically significant by ethnicity. Conclusions: Overall, diabetes significantly increased risk of all-cause mortality among women diagnosed with invasive BC from our study, particularly among Hispanic women. Diabetes was also found to be a significant prognostic factor for breast-cancer specific mortality. Future studies utilizing this data will be conducted to further evaluate the association between diabetes, glycemic control and breast cancer-specific mortality in Hispanic and NHW women. Citation Format: Connor AE, Visvanathan K, Boone SD, Baumgartner KB, Baumgartner RN. The association between type-2 diabetes and risk of mortality after invasive breast cancer among Hispanic and non-Hispanic white women from New Mexico [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-03.

Introduction: Soluble tumor necrosis factor receptor-II (sTNF-R2), a circulating pro-inflammatory biomarker, has been found to associated with obesity and increased risk of breast cancer. No studies to date have examined the association between sTNF-R2 and risk of mortality among Hispanic breast cancer survivors, an at-risk population due to their high prevalence of obesity and poor prognosis. The current study examined the long-term effects of sTNF-R2 on risk of mortality among Hispanic and non-Hispanic white (NHW) breast cancer survivors from the New Mexico Health Eating Activity and Lifestyle Study. Methods: A total of 397 invasive breast cancer survivors (96 Hispanic, 301 NHW) contributed data for the present study. Women with breast cancer diagnosed between July 1996 and March 1999 were ascertained through the National Cancer Institute's Surveillance Epidemiology and End Results registry in New Mexico. Baseline demographic characteristics, anthropometric measures, and blood samples were collected approximately 5 months post diagnosis by trained interviewers. Plasma levels of sTNF-R2 were assayed and measures were log-transformed to conform to normality. The main predictor of low (referent) vs high sTNF-R2 levels was based on the median value. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations between sTNF-R2 and all-cause mortality were calculated using Cox proportional hazards regression models overall and by ethnicity. Models were adjusted for age at diagnosis, education, breast cancer stage, treatment, and body mass index (BMI). Results: A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. While Hispanic women had higher baseline BMI (mean= 27.21, standard deviation (SD)= 5.83) compared to NHW women (mean= 25.68, SD= 5.36) (p< 0.001), significant differences by ethnicity for sTNF-R2 levels were not observed. In models adjusted for ethnicity and other covariates, the association between high vs low levels of plasma sTNF-R2 and risk of mortality was not statistically significant among all women (HR, 1.36; 95% CI 0.90-2.03). However, in models stratified by ethnicity, Hispanic women had increased risk of mortality of almost 3-fold (HR, 2.83; 95% CI 1.21-6.63), while the association among NHW women was attenuated and was not statistically significant (HR, 0.99; 95% CI 0.61-1.61). The statistical interaction between sTNF-R2 and ethnicity with risk of mortality was not statistically significant (p= 0.10). Conclusion: Our study results suggest Hispanic breast cancer survivors with high levels of systemic inflammation measured by sTNF-R2 are at increased risk of mortality. These results could inform targeted intervention studies to decrease inflammation and reduce risk of mortality among this at-risk population. Citation Format: Avonne E. Connor, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. Systemic inflammation is associated with increased risk of mortality after invasive breast cancer among Hispanic women from New Mexico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB081.

ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption. A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13–1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20–2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21–2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20–0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19–1.97). Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.

Traditional phase III clinical trials are powered to detect an overall treatment effect. However, it has increasingly been shown that many treatments are effective only for a subset of a population. The adaptive signature design uses genomic/proteomic information to prospectively predict a subset of patients more sensitive to treatment. Tests for overall treatment effect and for treatment effect in the predicted subset are conducted. In this work properties of the adaptive signature design are investigated through simulation. It was found that models which excluded expression main effect terms had higher empirical power than models which included them.

BACKGROUND: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispanic women. METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the U.S. and Mexico, we examined the association of breast-feeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, as well as the joint effects of breast-feeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER-PR-breast cancer. Increasing duration of breast-feeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR=0.73, 95% CI=0.60–0.89, P(trend) =0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breast-feeding further reduced HR+ breast cancer risk. Additionally, breast-feeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth. CONCLUSIONS: Our findings suggest that breast-feeding is associated with reduced risk of both HR+ and ER-PR-breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.

U.S. Hispanic women have high rates of parity, breastfeeding, and obesity. It is unclear whether these reproductive factors are associated with breast cancer (BC) mortality. We examined the associations between breastfeeding, parity, adiposity and BC-specific and overall mortality in Hispanic and non-Hispanic white (NHW) BC cases. The study population included 2921 parous women (1477 Hispanics, 1444 NHWs) from the Breast Cancer Health Disparities Study with invasive BC diagnosed between 1995 and 2004. Information on reproductive history and lifestyle factors was collected by in-person interview. Overall and stratified Cox proportional hazard regression models by ethnicity, parity, and body mass index (BMI) at age 30 years were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). After a median follow-up time of 11.2 years, a total of 679 deaths occurred. Pre-diagnostic breastfeeding was associated with a 16% reduction in mortality (HR 0.84; 95% 0.72–0.99) irrespective of ethnicity. Parity significantly modified the association between breastfeeding duration and mortality (p interaction = 0.05), with longer breastfeeding duration associated with lower risk among women who had ≤2 births (p trend = 0.02). Breastfeeding duration was associated with reduced risk of both BC-specific and overall mortality among women with BMI

Cervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination.Using electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14-26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression.Screening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45-3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09-4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21-4.48). Compared to unvaccinated women, women21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p0.0001).Women who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.

The contribution of type 2 diabetes and obesity on mortality in breast cancer (BC) patients has not been well studied among Hispanic women, in whom these exposures are highly prevalent. In a multi-center population-based study, we examined the associations between diabetes, multiple obesity measures, and mortality in 1180 Hispanic and 1298 non-Hispanic white (NHW) women who were diagnosed with incident invasive BC from the San Francisco Bay Area, New Mexico, Utah, Colorado, and Arizona. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years. In ethnic-stratified results, the association for BC-specific mortality among Hispanics was significantly increased (HR 1.85 95 % CI 1.11, 3.09), but the ethnic interaction was not statistically significant. In contrast, obesity at age 30 increased BC-specific mortality risk in NHW women (HR 2.33 95 % CI 1.36, 3.97) but not Hispanics (p-interaction = 0.045). Although there were no ethnic differences for all-cause mortality, diabetes, obesity at age 30, and post-diagnostic waist-hip ratio were significantly associated with all-cause mortality in all women. This study provides evidence that diabetes and adiposity, both modifiable, are prognostic factors among Hispanic and NHW BC patients.

Objective: Few epidemiological studies have included Hispanics with the evaluation of the effects of cigarette smoking and breast cancer. We examined the relationship between cigarette smoking, ethnicity, and breast cancer risk using data from the Breast Cancer Health Disparities Study (BCHDS). Materials and Methods: The BCHDS is a consortium of three population-based case–control studies, including U.S. non-Hispanic whites (NHWs) (1,525 cases; 1,593 controls), U.S. Hispanics/Native Americans (1,265 cases; 1,495 controls), and Mexican women (990 cases; 1,049 controls). Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Breast cancer risk was elevated among Mexican former smokers (OR 1.43, 95% CI 1.04–1.96) and among those who smoked ≥31 years (OR 1.95, 95% CI 1.13–3.35), compared to never smokers. In addition, Mexican former smokers with a history of alcohol consumption had increased breast cancer risk (OR 2.30, 95% CI 1.01–5.21)...

PurposeThere is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.MethodsThe study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.ResultsWhen comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95% CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95% CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.ConclusionsOur results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.

Background: Circulating markers of systemic inflammation have been found to be important long-term prognostic factors for breast cancer (BC). Studies have shown that obesity measured by percent body fat is the most significant predictor of inflammation in BC survivors. Specific BC treatments may also stimulate both local and systemic increases in inflammation. Little is known about the impact of other body size measures and BC treatment effects on inflammation among Hispanic BC survivors, an at-risk population due to their high prevalence of obesity and poor prognosis. Objective: We examined the associations between body size measures, BC treatment, and odds of systemic inflammation measured by soluble tumor necrosis factor receptor-II (sTNF-R2), a circulating pro-inflammatory biomarker, among Hispanic and non-Hispanic white (NHW) women diagnosed with breast cancer (stages I-IIIa) from the New Mexico Health, Eating, Activity, and Lifestyle cohort. Methods: A total of 397 BC survivors (96 Hispanic, 301 NHW) contributed data for the present study. Women with BC diagnosed between July 1996 and March 1999 were ascertained through the National Cancer Institute’s Surveillance Epidemiology and End Results registry in New Mexico. Baseline demographic characteristics, anthropometric measures, and blood samples were collected approximately 5 months post diagnosis by trained interviewers. Plasma levels of sTNF-R2 were assayed and measures were log-transformed to conform to normality. The study outcome of low vs high sTNF-R2 levels was based on the median value. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models and were stratified by ethnicity. Results: There were higher proportions of women with high compared to low sTNF-R2 levels and the following obesity measures: high percent body fat (≥35%), high body mass index (BMI) (≥30 kg/m2), and high waist-hip ratio (>0.85). No significant differences were observed by sTNF-R2 levels and ethnicity or treatment. In multivariable models, we observed significant positive associations among women with high body fat percentage (compared to < 35%) (OR= 1.62, 95% CI 1.01-2.60) and morbid obesity (BMI ≥35 kg/m2 compared to BMI< 35 kg/m2) (OR= 4.16, 95% CI 1.43-12.10). High waist-hip ratio was not significantly associated with sTNF-R2. While current tamoxifen use was not associated with sTNF-R2, we did find that women who received radiation and chemotherapy were 2 times more likely to have high sTNF-R2 levels compared to women who did not have chemotherapy and radiation (OR= 2.04, 95% CI 1.03-4.01). Our results were not significantly modified by ethnicity. Conclusion: BC survivors with high body fat percentage and extreme BMI have increased odds of systemic inflammation measured by sTNF-R2. Survivors treated with chemotherapy and radiation are also more likely to experience systemic inflammation. Future studies will examine the long-term effects of these associations on poor prognosis. Citation Format: Avonne E. Connor, Kala Visvanathan, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. Obesity, breast cancer treatment, and systemic inflammation: A cross- sectional analysis of Hispanic and non-Hispanic white breast cancer survivors from New Mexico [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-176.

Background: Epidemiologic studies primarily conducted in non-Hispanic white (NHW) women have found that elevated insulin levels, hyperinsulinemia, and chronic hyperglycemia (measured by hemoglobin A1c) are associated with poor prognosis in women diagnosed with breast cancer (BC). Only one study to date has included US Hispanic women, in whom diabetes is highly prevalent. Objective: We examined the associations between plasma fructosamine, a biomarker of hyperglycemia and glycemic control, self-reported diabetes, and risk of BC-specific and all-cause mortality among Hispanic and NHW women diagnosed with BC (stages I-IIIa) from the New Mexico Health, Eating, Activity, and Lifestyle (HEAL) Study. Methods: A total of 399 BC survivors (96 Hispanic, 303 NHW) contributed baseline data and plasma samples. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable Cox proportional hazards regression models. Models were adjusted for age at diagnosis, ethnicity, body size, education, BC stage and treatment. Results: After a median follow-up time of 13 years from baseline interview to death, a total of 134 deaths occurred, of which 56 deaths were attributed to BC. Approximately 38% of women with diabetes had clinically high fructosamine (> 285 μmol/L). While more Hispanic women had diabetes (11.5%) compared to NHW women (7.6%), significant differences by ethnicity for fructosamine levels were not observed (Hispanic mean= 236 μmol/L; NWH mean=238 μmol/L). Hispanics, however, had larger body size measures at baseline interview compared to NHW survivors. Diabetes was associated with increased BC mortality (HR, 2.89; 95% CI 1.27-6.60) and all-cause mortality (HR, 2.10; 95% CI 1.24-3.55). As a continuous measure, fructosamine was positively associated with BC-specific mortality (p=0.01) and with all-cause mortality, independent of diabetes history (p=0.001). Associations were strongest among women with clinically high fructosamine levels (BC: HR, 4.25; 95% CI 1.67-10.80; all-cause: HR, 2.32; 95% CI 1.30-4.14) compared to women with normal levels (≤285 μmol/L). Significant statistical interactions for associations by ethnicity were not observed. Conclusions: Our findings suggest that diabetes and fructosamine are significantly associated with increased risk of BC-specific and all-cause mortality among Hispanic and NHW women with invasive BC, even >10 years post diagnosis. Interventions to reduce BC mortality among ethnically diverse BC survivors should also consider methods to improve glycemic control among women with diabetes. Citation Format: Avonne E. Connor, Kala Visvanathan, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. The association between diabetes, plasma fructosamine, and risk of mortality after invasive breast cancer among Hispanic and non-Hispanic white women [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C077.

Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. For younger women, aged

This paper describes 2 “strategic partnering” and “interdisciplinary collaboration” case studies between a Center for Teaching and Learning (CTL) and an academic unit at a mid-sized metropolitan research university in the American Midwest. These faculty development partnerships were developed to meet the unique needs of faculty members who share a discipline area, present current information on specific teaching topics in order to deepen pedagogical knowledge and skills, provide opportunities for faculty to form a collegial group, and advance unit-specific goals relative to faculty development. The work is grounded in literature about the characteristics of a supportive teaching culture, characteristics of effective interdisciplinary collaborations, challenges of preparing faculty to conduct scholarly teaching, and in literature about the role of faculty development in advancing institutional change.

Treatment-related factors may increase the risk for arm lymphedema, which may occur after surgery or even many years after initial treatment for breast cancer. The association between treatment-related risk factors and development of arm lymphedema was examined for women who participated in the long-term quality of life (LTQOL) study, a 12–15-year follow-up of a breast cancer case–control study of Hispanic and non-Hispanic white women. Among 199 cases, 43 women (15 Hispanic, 28 non-Hispanic white) reported physician-diagnosed lymphedema during follow-up. Multivariable logistic regression analysis was used to calculate the odds ratios (OR) and 95 % confidence intervals (CI) for the association of risk factors with lymphedema, adjusting for relevant covariates. Tamoxifen had a non-significant, positive association with lymphedema (OR = 2.07, 95 % CI 0.94–4.55, p =0.07). There were no significant associations with type of surgery, radiation, or chemotherapy. Risk was increased specifically in overweight and obese women (body mass index (BMI) > =25 kg/m2) treated with tamoxifen (OR = 2.62, 95 % CI 0.99–6.93, p = 0.05). This study suggests that breast cancer survivors with a BMI >25 who report the use of tamoxifen therapy may be at increased risk for arm lymphedema. Larger case–control studies and clinical trials should investigate the long-term association of tamoxifen treatment with arm lymphedema especially in overweight and obese women. Lymphedema risk may be another indication to consider a weight reduction program in breast cancer survivors.

Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 ancestry informative markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and estrogen receptor (ER)/progesterone receptor (PR) strata. MAP3K9 was associated with breast cancer overall (P(ARTP) = 0.02) with strongest association among women with the highest IA ancestry (P(ARTP) = 0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate, and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations.

It is widely recognized that many cancer therapies are effective only for a subset of patients. However clinical studies are most often powered to detect an overall treatment effect. To address this issue, classification methods are increasingly being used to predict a subset of patients which respond differently to treatment. This study begins with a brief history of classifi- cation methods with an emphasis on applications involving melanoma. Nonparametric methods suitable for predicting subsets of patients responding differently to treatment are then reviewed. Each method has different ways of incorporating continuous, categorical, clinical and high-throughput covariates. More recent methods have built-in dimension reduction methods for high throughput data. Pre-validation is one method of assessing the added value of high-throughput data to clinical covariates. The way in which treatment interactions are incorporated is important if the goal is to predict a subset of patients which respond differently to treatment. For nonparametric methods, distance measures specific to the method are used to make classification decisions. Approaches are outlined which employ these distances to measure treatment interactions. It is hoped that this study will stimulate more development of nonparametric methods to predict subsets of patients responding differently to treatment.

Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14–26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population., Highlights • Screening rates are extremely low (24%) among those targeted for HPV vaccination. • Screening rates are 84% if vaccinated at 21 years or older. • Only HPV vaccination at ages closer to 21 years predicts screening participation. • 3 dose recipients are more likely than unvaccinated to continue screening after NILM. • Only 50% of vaccinated women continue to screen after a NILM result.

Background: Few studies in Hispanic women have examined the relation between adult body size and risk of premenopausal breast cancer defined by hormone receptor status. Methods: The Breast Cancer Health Disparities Study pooled interview and anthropometric data from two large U.S. population-based case–control studies. We examined associations of overall and abdominal adiposity with risk of estrogen receptor– and progesterone receptor–positive (ER+PR+) and –negative (ER−PR−) breast cancer in Hispanic and non-Hispanic White (NHW) women, calculating ORs and 95% confidence intervals. Results: Among Hispanics, risk of ER+PR+ breast cancer was inversely associated with measures of overall adiposity, including young-adult and current body mass index (BMI). Risk was substantially reduced among those with high (above the median) young-adult BMI and current overweight or obesity. The findings for overall adiposity were similar for Hispanics and NHWs. In the subset of Hispanics with data on genetic ancestry, inverse associations of current BMI, and weight gain with ER+PR+ breast cancer were limited to those with lower Indigenous American ancestry. For ER−PR− breast cancer, height was associated with increased risk, and young-adult BMI was associated with reduced risk. For all breast cancers combined, positive associations were seen for waist circumference, waist-to-hip ratio, and waist-to-height ratio in Hispanic women only. Conclusions: Our findings of body size associations with specific breast cancer subtypes among premenopausal Hispanic women were similar to those reported for NHW women. Impact: Adiposity throughout the premenopausal years has a major influence on breast cancer risk in Hispanic women. Cancer Epidemiol Biomarkers Prev; 24(1); 138–47. ©2014 AACR. See related article by John et al., p. 128

Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. We investigated associations between TNF-α −308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1 Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I–IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years). Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10–0.83] and all-cause mortality (HR 0.51; 95% CI 0.28–0.91). Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α −308 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.

The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants’ waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over *9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HR(q4:q1): 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specificmortality was not statistically significant (HR(q4:q1): 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HR(q4:q1): 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HR(q4:q1): 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.

PURPOSE: A comprehensive understanding of the role of modifiable health behaviors in effective management of cancer-related fatigue is needed. Among breast cancer survivors, we examined how postdiagnosis diet quality, independently and jointly with physical activity, is related to fatigue, and the potential mediating role of inflammation. METHODS: 770 women diagnosed with stage 0-IIIA breast cancer in the Health, Eating, Activity, and Lifestyle study completed food frequency and physical activity questionnaires 30-months postdiagnosis. We scored diet quality using the Healthy Eating Index-2010 (HEI-2010). Serum concentrations of C-reactive protein (CRP) were measured in fasting 30-ml blood samples. Multidimensional fatigue was measured 41-months postdiagnosis using the 22-item revised Piper Fatigue Scale. In multivariate linear models, we determined whether fatigue was associated HEI-2010 quartiles (Q1-Q4), and a variable jointly reflecting HEI quartiles and physical activity levels. RESULTS: Survivors with better quality diets (Q4 vs. Q1) had lower total fatigue (4.1 vs. 4.8, p-contrast=0.003) and subscale scores (behavioral severity: 3.4 vs. 4.2, p-contrast=0.003; affective meaning: 3.9 vs. 4.8, p-contrast=0.007; sensory: 4.4 vs. 5.2, p-contrast=0.003; cognitive: 4.6 vs. 5.0, p-contrast=0.046). Least squares estimates of fatigue were similar in models including CRP. Compared to survivors with poor quality diets and no physical activity, survivors with better quality diets and meeting physical activity recommendations had significantly lower behavioral severity (3.2 vs. 4.7, p-contrast=0.002) and sensory (3.8 vs. 4.8. p-contrast=0.006) fatigue scores. CONCLUSION: In this large breast cancer survivor cohort, postdiagnosis diet quality was inversely and independently associated with fatigue. IMPLICATIONS: Future interventions designed to improve multiple energy balance behaviors can provide insight into their associations with fatigue.

Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.

Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown. Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study. Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00–1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29–2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI 30: OR = 0.65 (95% CI, 0.44–0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29–0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry. Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry. Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692–701. ©2016 AACR.

Some studies suggest that Hispanic women are more likely to have ER− and triple-negative (ER−/PR−/HER2−) tumors and subsequently poorer prognosis than non-Hispanic white (NHW) women. In addition, only a handful of studies have examined period-specific effects of tumor phenotype and ethnicity on breast cancer survival, leaving the time-varying effects of hormonal status and ethnicity on breast cancer survival poorly defined. This study describes short and long-term breast cancer survival by ethnicity at 0–5 years and 5+ years post-diagnosis using data from the New Mexico Health, Eating, Activity, and Lifestyle cohort of Hispanic and NHW women ages 29–88 years newly diagnosed with stages I–IIIA breast cancer. The survival rate for Hispanics at 0–5 years was 82.2 % versus 94.3 % for NHW. Hispanics were more likely to have larger tumors, more advanced stage, and ER− phenotypes compared to NHW women. There was a significantly higher risk of breast cancer mortality in Hispanics over 5 years of follow-up compared to NHW (HR = 2.78, 95 % CI 1.39–5.56), adjusting for age, tumor phenotype, stage, and tumor size. This ethnic difference in survival, however, was attenuated and no longer statistically significant when additional adjustment was made for education, although a >1.5-fold increase in mortality was observed. In contrast, there was no difference between ethnic groups for survival after 5 years (HR = 1.08, 95 % CI 0.36–3.24). Our results indicate that the difference in survival between Hispanic and NHW women with breast cancer occurs in the first few years following diagnosis and is jointly associated with tumor phenotype and socio-demographic factors related to education.

Angiogenesis is essential for tumor development and progression. Genetic variation in angiogenesis-related genes may influence breast carcinogenesis. We evaluated dietary factors associated with oxidative balance, DDIT4 (one SNP), FLT1 (35 SNPs), HIF1A (four SNPs), KDR (19 SNPs), MPO (one SNP), NOS2A (15 SNPs), TEK (40 SNPs) and VEGFA (eight SNPs) and breast cancer risk among Hispanic (2,111 cases and 2,597 controls) and non-Hispanic white (1,481 cases and 1,586 controls) women in the Breast Cancer Health Disparities Study. Adaptive rank truncated product (ARTP) analysis was used to determine gene and pathway significance with breast cancer. TEK was associated with breast cancer overall (pARTP = 0.03) and with breast cancer survival (pARTP = 0.01). KDR was of borderline significance overall (pARTP = 0.07), although significantly associated with breast cancer in both low and intermediate Native American (NA) ancestry groups (pARTP = 0.02) and estrogen receptor (ER)+/progesterone receptor (PR)− tumor phenotype (pARTP = 0.008). Both VEGFA and NOS2A were associated with ER−/PR− tumor phenotype (pARTP = 0.01 and pARTP = 0.04, respectively). FLT1 was associated with breast cancer survival among those with low NA ancestry (pARTP = 0.009). With respect to diet, having a higher dietary oxidative balance score (DOBS) was significantly associated with lower breast cancer risk [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.64–0.84], with the strongest associations observed for women with the highest NA ancestry (OR 0.44, 95% CI 0.30–0.65). We observed few interactions between DOBS and angiogenesis-related genes. Our data suggest that dietary factors and genetic variation in angiogenesis-related genes contribute to breast cancer carcinogenesis.

The TGF-β signaling pathway has a significant role in breast cancer initiation and promotion by regulating various cellular processes. We evaluated whether genetic variation in eight genes (TGF-β1, TGF-β2, TGF-βR1, TGF-βR2, TGF-βR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in women from the Breast Cancer Health Disparities Study. A total of 3,524 cases (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209 population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were determined. Additionally, 104 ancestral informative markers estimated proportion of NA ancestry. Associations with breast cancer risk overall, by menopausal status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor phenotype were evaluated. After adjustment for multiple comparisons, two SNPs were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG = 1.15 95 % CI 1.04–1.26) and TGF-β1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81–0.98). RUNX3 (rs906296) and TGF-βR2 (rs3773644) were associated with risk in pre-menopausal women (p adj = 0.002 and 0.02, respectively) and in those with intermediate to high NA ancestry (p adj = 0.04 and 0.01, respectively). Self-reported race was strongly correlated with NA ancestry (r = 0.86). There was a significant interaction between NA ancestry and RUNX1 (rs7279383, p adj = 0.04). Four RUNX SNPs were associated with increased risk of ER− tumors. Results provide evidence that genetic variation in TGF-β and RUNX genes are associated with breast cancer risk. This is the first report of significant associations between genetic variants in TGF-β and RUNX genes and breast cancer risk among women of NA ancestry.

Growth factors (GF) stimulate cell proliferation through binding to cell membrane receptors and are thought to be involved in cancer risk and survival. We examined how genetic variation in epidermal growth factor (EGF), neuregulin 2 (NRG2), ERBB2 (HER2/neu), fibroblast growth factors 1 and 2 (FGF1 and FGF2) and its receptor 2 (FGFR2), and platelet-derived growth factor B (PDGFB) independently and collectively influence breast cancer risk and survival. We analyzed data from the Breast Cancer Health Disparities Study which includes Hispanic (2,111 cases, 2,597 controls) and non-Hispanic white (1,481 cases, 1,586 controls) women. Adaptive rank-truncated product (ARTP) analysis was conducted to determine gene significance. Odds ratios (OR) and 95 % confidence intervals were obtained from conditional logistic regression models to estimate breast cancer risk and Cox proportional hazard models were used to estimate hazard ratios (HR) of dying from breast cancer. We assessed Native American (NA) ancestry using 104 ancestry informative markers. We observed few significant associations with breast cancer risk overall or by menopausal status other than for FGFR2 rs2981582. This SNP was significantly associated with ER+/PR+ (OR 1.66, 95 % CI 1.37–2.00) and ER+/PR− (OR 1.54, 95 % CI 1.03–2.31) tumors. Multiple SNPs in FGF1, FGF2, and NRG2 significantly interacted with multiple SNPs in EGFR, ERBB2, FGFR2, and PDGFB, suggesting that breast cancer risk is dependent on the collective effects of genetic variants in other GFs. Both FGF1 and ERBB2 significantly influenced overall survival, especially among women with low levels of NA ancestry (P ARTP = 0.007 and 0.003, respectively). Our findings suggest that genetic variants in growth factors signaling appear to influence breast cancer risk through their combined effects. Genetic variation in ERBB2 and FGF1 appear to be associated with survival after diagnosis with breast cancer.

Background: Physical activity is associated with reduced mortality and higher quality of life in breast cancer survivors; however, limited data on the prevalence of activity and long-term trends after diagnosis are available. Methods: A multiethnic cohort of 631 women (18–64 years) with stage 0 to IIIA breast cancer was followed for 10 years. Recreational aerobic activity (MET-h/wk) was ascertained for the year before diagnosis (baseline), 24 months, 5 years, and 10 years after enrollment. Women were classified according to U.S. physical activity guidelines (≥150 min/wk moderate or ≥75 min/wk vigorous activity). The OR for meeting guidelines at 5 and 10 years according to baseline factors was estimated using logistic regression. The change in MET-h/wk was predicted using linear regression. Results: Prediagnosis, 34% of women met physical activity guidelines; 34.0%, 39.5%, and 21.4% met guidelines at 24 months, 5 years, and 10 years after enrollment, respectively. Less than 8% of survivors met guidelines at all follow-up periods. Over 10 years, recreational aerobic activity decreased by a mean ± SD of 4.3 ± 16.2 MET-h/wk. Meeting guidelines pre-diagnosis was strongly associated with meeting guidelines at 5 years [OR (95% confidence interval; CI): 2.76 (1.85–4.1)] and 10 years [OR (95% CI): 3.35 (2.13–5.28)]. No other demographic or prognostic factors were significantly associated with the 10-year change in MET-h/wk. Conclusion: The vast majority of early breast cancer survivors do not meet national exercise recommendations 10 years postdiagnosis. Impact: Physical activity levels are low in breast cancer survivors across the 10 years postdiagnosis; nonetheless, the predictors of activity in this population remain poorly understood. Cancer Epidemiol Biomarkers Prev; 22(6); 1153–61. ©2013 AACR.