Avonne E. Connor

Obesity and Risk of Breast Cancer Mortality in Hispanic and Non-Hispanic White Women: The New Mexico Women's Health Study

Obesity is reported to be associated with poorer survival in women with breast cancer, regardless of menopausal status. Our purpose was to determine if the associations of obesity with breast cancer-specific, all-cause, and non-breast cancer mortality differ between Hispanic and non-Hispanic white (NHW) women with breast cancer. Data on lifestyle and medical history were collected for incident primary breast cancer cases (298 NHW, 279 Hispanic) in the New Mexico Womens Health Study. Mortality was ascertained through the National Death Index and New Mexico Tumor Registry over 13 years of follow-up. Adjusted Cox regression models indicated a trend towards increased risk for breast cancer-specific mortality in obese NHW women (hazard ratio [HR] 2.07; 95% confidence interval [CI] 0.98-4.35) but not in Hispanic women (HR 1.32; 95% CI 0.64-2.74). Obese NHW women had a statistically significant increased risk for all-cause mortality (HR 2.12; 95% CI 1.15-3.90) while Hispanic women did not (HR 1.23; 95% CI 0.71-2.12). Results were similar for non-breast cancer mortality: NHW (HR 2.65; 95% CI 0.90-7.81); Hispanic (HR 2.18; 95% CI 0.77-6.10). Our results suggest that obesity is associated with increased risk for breast cancer-specific mortality in NHW women; however, this association is attenuated in Hispanic women.

Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study

Chronic inflammation is suggested to be associated with specific cancer sites, including breast cancer. Recent research has focused on the roles of genes involved in the leukotriene/lipoxygenase and prostaglandin/cyclooxygenase pathways in breast cancer etiology. We hypothesized that genes in ALOX/COX pathways and CRP polymorphisms would be associated with breast cancer risk and mortality in our sample of Hispanic/Native American (NA) (1430 cases, 1599 controls) and non‐Hispanic white (NHW) (2093 cases, 2610 controls) women. A total of 104 Ancestral Informative Markers was used to distinguish European and NA ancestry. The adaptive rank truncated product (ARTP) method was used to determine the significance of associations for each gene and the inflammation pathway with breast cancer risk and by NA ancestry. Overall, the pathway was associated with breast cancer risk (PARTP = 0.01). Two‐way interactions with NA ancestry (Padj < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194). We observed increases in breast cancer risk in stratified analyses by tertiles of polyunsaturated fat intake for ALOX12 polymorphisms; the largest increase in risk was among women in the highest tertile with ALOX12 rs9904779CC (Odds Ratio (OR), 1.49; 95% Confidence Interval (CI) 1.14‐1.94, Padj = 0.01). In a sub‐analysis stratified by NSAIDs use, two‐way interactions with NSAIDs use were found for ALOX12 rs9904779 (Padj = 0.02), rs434473 (Padj = 0.02), and rs1126667 (Padj =  0.01); ORs for ALOX12 polymorphisms ranged from 1.55 to 1.64 among regular users. Associations were not observed with breast cancer mortality. These findings could support advances in the discovery of new pathways related to inflammation for breast cancer treatment.

Cigarette Smoking and Breast Cancer Risk in Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study

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). Among NHW premenopausal women, breast cancer risk was increased for smoking ≥ 20 cigarettes per day (OR 1.61, 95% CI 1.07-2.41). CONCLUSION Our findings suggest the possibility of ethnic differences with the associations between cigarette smoking and breast cancer risk.

Differences between Hispanic and non-Hispanic white women with breast cancer for clinical characteristics and their correlates

PURPOSE Body size and ethnicity may influence breast cancer tumor characteristics at diagnosis. We compared Hispanic and non-Hispanic white (NHW) cases for stage of disease, estrogen receptor (ER) status, tumor size, and lymph node status, and the associations of these with body size in the 4-Corners Breast Cancer Study. METHODS One thousand five hundred twenty-seven NHW and 798 Hispanic primary incident breast cancer cases diagnosed between October 1999 and May 2004 were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression. RESULTS Hispanic women were more likely to have larger (>1 cm) ER- tumors and more than four positive lymph nodes (P < .003). Lymph node status was not associated with body size. However, among NHW women, obesity (body mass index >30) and increased waist circumference (>38.5 inches) were significantly positively associated with ER- tumor status (OR, 1.87; 95% CI, 1.24-2.81 and OR, 2.59; 95% CI, 1.58-4.22, respectively). In contrast, among Hispanic women, obesity and waist circumference had inverse associations with ER- tumor status (OR, 0.49; 95% CI, 0.29-0.84 and OR, 0.56; 95% CI, 0.30-1.05, respectively). CONCLUSIONS Hispanic ethnicity may modify the association of body size and composition with ER- breast cancer. This finding could have relevance to clinical treatment and prognosis.

Abstract LB-363: Breastfeeding, parity and risk of mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study

Background: A history of breastfeeding was recently shown to be associated with a 48% reduction in breast cancer (BC) mortality, particularly luminal A subtype. Hispanic women have higher parity and are more likely to breastfeed compared to non-Hispanic white (NHW) women. Thus breastfeeding may be an important modifiable prognostic factor for Hispanic women diagnosed with BC. We examined the associations between breastfeeding, parity and BC-specific and overall mortality in Hispanic and NHW BC survivors. Methods: The study population included 2,921 parous women (1,477 Hispanics, 1,444 NHWs) from the San Francisco Bay Area, New Mexico, Utah, Colorado and Arizona with incident, invasive BC diagnosed between April 1995 and April 2002 or between October 1999 and May 2004, depending on study site. Information on reproductive history and lifestyle factors was collected by in-person interview. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards regression models for overall associations and by estrogen receptor (ER) status, adjusting for study site, ethnicity, age at diagnosis, BC stage, parity, age at first and last full-term pregnancy, pregnancy duration in years, body mass index, waist circumference, and waist-hip ratio. Results: The median follow-up time was 11.2 years since BC diagnosis, with a total of 679 deaths from any cause. A history of breastfeeding was reported by 50.4% of Hispanic cases and 49.6% of NHW cases. Breastfeeding was associated with reduced risk of overall mortality (HR, 0.84; 95% CI 0.72-0.99) adjusting for age, BC stage, parity and ethnicity. The association between breastfeeding and overall mortality was stronger for women diagnosed with estrogen receptor negative (ER-) tumors (HR, 0.69; 95% CI 0.48-0.99). While breastfeeding for ?6 months was not associated with reduced overall mortality (HR, 0.84; 95% CI 0.57-1.25) among women with ER- BC, a reduction of 52% was found for those breastfeeding for Conclusions: Breastfeeding was associated with reduced mortality, particularly among women with ER- tumors in whom there are few modifiable prognostic factors. These results provide another reason to encourage breastfeeding among young women. Citation Format: Avonne E. Connor, Kala Visvanathan, Kathy B. Baumgartner, Richard N. Baumgartner, Stephanie D. Boone, Lisa M. Hines, Anna R. Giuliano, Esther M. John, Roger K. Wolff, Martha L. Slattery. Breastfeeding, parity and risk of mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study. [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 LB-363.

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

Importance The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures Invasive or in situ premenopausal breast cancer. Results Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor–positive and/or progesterone receptor–positive than for hormone receptor–negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor–positive and progesterone receptor–positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor–negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor–negative breast cancer overall. Conclusions and Relevance The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

Abstract 5311: Weight loss over 10 years of adulthood and subsequent risk of breast cancer: a pooled analysis of 11 cohort studies

Body fatness is an established risk factor for postmenopausal breast cancer, but it is unknown if this risk associated with excess body weight is reversible. We conducted a pooled analysis of 11 prospective studies in the Pooling Project of Prospective Studies of Diet and Cancer. Each study had adult body weight data at three time points, as well as follow-up for subsequent risk of breast cancer after the third weight measure. Weight change was assessed using reported or measured weight at baseline and two follow-up time points, each generally four to six years apart (over a total of ~10 years). Stable weight for each interval was defined as weight within 2kg of the previous weight. The referent group was women with stable weight (within 2kg) at all three time points across the 10-year period. Among 340,055 women, 10,427 breast cancers were diagnosed during follow-up. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) controlling for baseline body mass index (BMI), baseline physical activity, and postmenopausal hormone (PMH) use at the start of breast cancer follow-up, were estimated using proportional hazards regression on an aggregated dataset from all studies. Women who lost weight and kept the weight off, were at a lower risk of breast cancer than women with stable weight over the 10 years: >2.-4.5kg lost between baseline and the first follow-up body weight measure (n=482 cases): HR=0.92, 95% CI: 0.83-1.03; >4.5-9kg lost (n=283 cases): HR=0.86, 95% CI: 0.76-0.98; >9kg lost (n=95 cases): HR =0.81, 95%CI: 0.65-1.00). Women who initially lost weight (>2kg), but then re-gained it had a similar risk of breast cancer to those with stable weight over the same time period. When results were stratified by baseline age and BMI, there was no association between sustained weight loss and breast cancer among women younger than 50 years, nor those with a normal BMI (18.5-25 kg/m2) before weight loss. Among women who were aged 50 or more years and overweight or obese before the weight loss period, we observed a 21% lower risk of breast cancer for sustained weight loss of ≥4.5kg compared to women with stable weight over the same time period (n=245 cases, HR=0.79, 95% CI: 0.68-0.93). This observed association was driven by women who were not taking PMH (n=156, HR=0.71, 95% CI: 0.58-0.86). In this large, pooled prospective analysis of weight loss and breast cancer risk we found that losing 4.5 kg—and keeping it off—may lower breast cancer risk, particularly for women older than 50 who are overweight or obese. The results may provide motivation for women with elevated BMI to lose weight and potentially reduce their risk of breast cancer. Citation Format: Lauren R. Teras, Alpa V. Patel, Molin Wang, Bette J. Caan, Yu Chen, Avonne E. Connor, A. Heather Eliassen, Susan M. Gapstur, Mia M. Gaudet, Jeanine M. Genkinger, Graham G. Giles, I-Min Lee, Roger Milne, Norie Sawada, Howard D. Sesso, Meir Stampfer, Rulla Tamimi, Cynthia A. Thomson, Shoichiro Tsugane, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Walter C. Willett, Stephanie A. Smith-Warner. Weight loss over 10 years of adulthood and subsequent risk of breast cancer: a pooled analysis of 11 cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2017-5311

Abstract 799: Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study

Previously, we reported associations between breast cancer (BC) risk and tuna intake in non-Hispanic White (NHW) and Hispanic women, and processed meat intake among Hispanic women only. We also reported associations with SNPs in genes involved in the Convergence of Hormones, Inflammation, and Energy-related Factors (CHIEF) network. Given the multifactorial nature of BC etiology, we tested for interactions (GxE) between meat/fish intake and SNPs in selected CHIEF pathways using a set-based method that aggregates SNPs into groups for GxE association testing.The study population included Hispanic (1046 cases, 1331 controls) and NHW (1234 cases, 1468 controls) women from two US population-based case-control studies that are part of the Breast Cancer Health Disparities Study. Harmonized meat intake variables were dichotomized, and include red meat, processed meat, poultry, fish, and tuna. 734 SNPs were grouped into 107 genes based on loci. Genes were further grouped into 7 pathways based on biological function: CHIEF core, ALOX/COX, Interleukins, JAK/STAT/SOC, TLR/TNF, MAPK, and TGF-â. We performed the analysis in a top-down fashion, sequentially testing for interactions between meat/fish intake and pathways, genes within pathways, and SNPs within genes. To test pathways and genes, we used a set-based GxE approach that extends the adaptive rank truncated product (ARTP), and to test individual SNPs we used logistic regression. At gene and SNP level analyses, we applied Bonferroni corrections for the number of genes or SNPs tested. Analyses were stratified by ethnicity. Models were adjusted for study, age, education, menopausal status, family history of breast cancer, parity, body mass index, physical activity, education, intake of alcohol, fiber, calories, fat, carbohydrates, proteins, and genetic ancestry. We report results that showed statistically significant interactions at both pathway and gene levels. Analyses were conducted using the R programming language. Among NHW women, pathway-level analyses using ARTP identified an interaction between poultry intake and the interleukin/cytokine pathway, which was driven by the IL17A gene (2 SNPs); poultry intake was inversely associated with BC risk among carriers of the minor alleles in this gene. Among Hispanics, ARTP analyses identified an interaction between tuna intake and total fish intake and the Jak/Stat/SOC pathway, which was driven by STAT5A (tuna: 2 SNPs) and STAT5B (total fish and tuna: 3 SNPs). The positive associations between fish or tuna and BC risk were restricted to carriers of minor alleles in these two genes. Overall, our findings suggest a role for poultry and fish intake in chronic inflammation and tumor growth promotion in breast carcinogenesis and highlight specific genes that may play roles in these carcinogenic pathways. Citation Format: Andre E. Kim, Juan Pablo Lewinger, Shirong Zhang, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Jennifer S. Herrick, Stephanie D. Boone, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna Giuliano, Martha L. Slattery, Mariana C. Stern. Interaction between meat and fish intake and genes involved in hormones, inflammation and energetic factors, and risk of breast cancer among Hispanic and Non-Hispanic White women: The Breast Cancer Health Disparities Study. [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 799.

Abstract C51: Ethnic differences in the relationship between diabetes, early age adiposity, and mortality among breast cancer survivors: The Breast Cancer Health Disparities Study

Hispanic women have a high prevalence of type 2 diabetes and obesity. Breast cancer (BC) has become the leading cause of death among Hispanic women. Limited information exists on the relationship between diabetes, obesity, and mortality in Hispanic women diagnosed with BC. In a multicenter study we examined the associations between diabetes, obesity measures and survival outcomes. The study included 1,180 Hispanic and 1,298 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 by Cox proportional hazards regression models. The median follow-up time from BC diagnosis to death was 10.8 years and 267 of 466 deaths that occurred were from BC. Diabetes was significantly associated with BC-specific mortality (HR, 1.63 95% CI 1.08-2.47), with a stronger association among Hispanics (HR, 1.85 95% CI 1.11-3.09) compared to NHWs (HR, 1.33 95% CI 0.67-2.62). Among diabetic Hispanic women with estrogen receptor negative tumors, BC-specific mortality was increased three-fold (HR, 2.93 95% CI 1.09-7.88). In contrast, obesity at age 30 years was positively associated with BC-specific mortality in NHW women after adjusting for diabetes and known prognostic factors (HR, 2.33 95% CI 1.36-3.97, p interaction Citation Format: Avonne E. Connor, Kala Visvanathan, Kathy B. Baumgartner, Richard N. Baumgartner, Stephanie D. Boone, Lisa M. Hines, Anna R, Giuliano, Roger K. Wolff, Esther M. John, Martha L. Slattery. Ethnic differences in the relationship between diabetes, early age adiposity, and mortality among breast cancer survivors: The Breast Cancer Health Disparities Study. [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 C51.

Abstract 1276: Red meat, poultry, and fish intake, genetic risk variants, and breast cancer risk among Hispanic and non-Hispanic white women: Results from the Breast Cancer Health Disparities Study

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Purpose: Breast cancer (BC) incidence rates are lower among US Hispanics compared to non-Hispanic white (NHW) women, and the proportion of Native American (NA) ancestry among Hispanic women is associated with BC risk. Meat intake is inconsistently associated with BC risk, though few studies have included Hispanic women. We investigated: a) the association between various meats and BC risk among Hispanic/NA and NHW women, and b) the potential interaction of meat intake with GWAS-identified risk variants. Methods: The Breast Cancer Health Disparities consortium includes 3 population-based case-control studies conducted in the US and Mexico (N=4410 NHW, N=6163 Hispanic/NA). BC risk factor data and dietary intake were assessed by questionnaires. Five meat variables (gm/day) were harmonized across the 3 studies: red meat, processed red meat, poultry, fish, and tuna. We considered nutrient density variables, created with study-specific cut-points based on intake distribution among controls. Ten GWAS identified SNPs were genotyped, in addition to 104 Ancestry Informative Markers that were used to categorize participants by percent NA ancestry using STRUCTURE (Low: 0-28%; Intermediate: 29-70%; High: >70%). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of the association between meat variables and BC risk, stratified by menopause status, ethnicity, and, within Hispanics/NA, by percent NA ancestry. Interaction P values were obtained from likelihood ratio tests. Results: Among all women, processed meat was positively associated with pre-menopausal BC risk (Q3 vs. Q1 OR = 1.31; 95% CI = 1.08-1.55; trend p = 0.004; heterogeneity p = 0.027). This association appeared restricted to Hispanic/NA women, albeit a test of heterogeneity by ethnicity was not statistically significant. We also observed a positive association between tuna and BC risk only among pre-menopausal NHW women (Q3 vs. Q1 OR = 1.41; 95% CI = 1.06-1.87; trend p = 0.007; heterogeneity p = 0.007). Among post-menopausal women a positive association between red meat and BC risk only among Hispanic/NA women of low percent NA ancestry (Q3 vs. Q1 OR = 2.06; 95% CI = 1.08-3.91; trend p = 0.037; heterogeneity p = 0.02) was observed. After multiple testing correction marginally significant interactions among NHW women between intake of processed meat and rs3803662-TOX3 (corrected int p = 0.06) and between intake of tuna and rs2067980 (corrected int p = 0.06) were detected. Conclusion: Diets high in processed meats and tuna are associated with elevated BC risk among pre-menopausal Hispanic/NA and NHW women, respectively. Diets high in red meat are associated with elevated BC risk among post-menopausal Hispanic/NA women with low NA ancestry. Citation Format: Andre E. Kim, Mariana C. Stern, Abbie Lundgreen, Juan Pablo Lewinger, Roger K. Wolff, Laura Fejerman, Esther M. John, Gabriela Torres-Mejia, Sue A. Ingles, Avonne E. Connor, Lisa M. Hines, Kathy B. Baumgartner, Anna R. Giuliano, Martha L. Slattery. Red meat, poultry, and fish intake, genetic risk variants, and breast cancer risk among Hispanic and non-Hispanic white women: Results from the Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1276. doi:10.1158/1538-7445.AM2014-1276