Stephanie D. Boone

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.

Associations between prior HPV4 vaccine doses and cervical cancer screening participation.

BACKGROUND 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. METHODS 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. RESULTS 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, women <21y 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 (p<0.0001). CONCLUSIONS 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.

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.

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 C86: Active smoking and breast cancer risk among Hispanic and non-Hispanic white women from the Breast Cancer Health Disparities Study

The association between smoking and breast cancer has been extensively evaluated in epidemiological studies. Some, but not all studies found a positive association between smoking and breast cancer risk, especially among women with long smoking duration. Few studies have included Hispanic women. We evaluated the interaction between active smoking exposure and ethnicity using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies including U.S. non-Hispanic whites (NHW) (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). Using multivariable logistic regression, odds ratios (ORs) and 95% confidence intervals (CI) were calculated to estimate the risk of breast cancer associated with active smoking exposure and assess differences in associations by ethnicity. We also tested for interaction effects between smoking and ethnicity by menopausal status and by history of alcohol use. Assessment of tobacco usage and active smoking exposures by ethnicity showed that there were significant (p value Citation Format: Avonne E. Connor, Kathy B. Baumgartner, Richard N. Baumgartner, Christina M. Pinkston, Stephanie D. Boone, Esther M. John, Gabriela Torres- Mejia, Lisa M. Hines, Anna R. Giuliano, Roger K. Wolff, Martha L. Slattery. Active smoking and breast cancer risk among Hispanic and non-Hispanic white women from the Breast Cancer Health Disparities Study. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C86. doi:10.1158/1538-7755.DISP13-C86

Abstract C87: Risk of second primary cancer (SPC) after breast cancer: A pooled analysis of Hispanic and non-Hispanic white women from New Mexico

Breast cancer is the most common form of cancer diagnosed among women. With the advances in early detection and breast cancer treatment, the population of long-term survivors is growing. Breast cancer survivors have increased risk of developing a second primary cancer (SPC) relative to a first primary cancer. Several population-based studies have examined the associations of specific risk factors, such as radiation treatment, with risk of SPC; however, few have investigated ethnic/racial differences in risk, or have examined the associations with modifiable risk factors such as smoking or obesity. We evaluated the risk of SPC among Hispanic (H) and non-Hispanic white (NHW) women from a pooled sample of 1,699 (1011 NHW, 688 H) incident breast cancer cases from the New Mexico Women9s Health Study (1992-1994) and the 4-Corner9s Breast Cancer Study (1999-2004). Data on lifestyle/behavioral risk factors, cancer diagnoses/characteristics, and primary breast cancer treatment were available. Adjusted Cox regression models were calculated to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of SPC with ethnicity, age at first primary breast cancer diagnosis, cigarette smoking history, and obesity (body mass index (BMI)≥30 kg/m 2 ). Multivariable models were adjusted for age, study site/center, ethnicity, and breast cancer treatment. There were a total of 223 cases with SPC. There was no difference between NHW and H women for occurrence of SPC (13.5% vs. 12.7%; chi. sq. p=0.63) or the average number of years from first primary to SPC (H= 9.8 years vs. NHW= 9.5 years, p=0.102). The most common SPC observed was secondary primary breast cancer (n=117), followed by lung (n=15) and colon cancer (n=15). Obesity was not significantly associated with risk of SPC. However, women 50 years or older were at an increased risk for SPC compared to women under age 50 (HR, 1.67, 95% CI 1.23-2.28, p=0.001). With the evaluation of smoking history, former smokers had longer durations of smoking compared to current smokers; however, current smokers, compared to former, smoked on average more cigarettes/day. Compared to never smokers, women who smoked more than 20 pack-years (HR, 1.61; 95% CI 1.16-2.24, p=0.02), an average of 20 or more cigarettes/day (HR, 1.52; 95% CI 1.10-2.10, p=0.09), or for more than 30 years (HR, 1.69; 95% CI 1.19-2.40, p=0.03) had increased risk for SPC. Women who were ever smokers vs. never smokers also had an increased risk for SPC (HR, 1.35; 95% CI 1.04-1.76, p=0.03). The association among current smokers was not statistically significant (HR, 1.27; 95% CI 0.94-1.71), but there was a significant positive association found for former smokers (HR, 1.52; 95% CI 1.06-2.18, p=0.05). Our results suggest that women diagnosed with primary breast cancer are more likely to develop SPC if they are over the age of 50 years at diagnosis or have a history of cigarette smoking. These results were statistically significant after adjustment for breast cancer treatment. These findings further suggest that smoking cessation programs or interventions should be clinically advised for breast cancer survivors, as this population of women is at an increased risk for developing SPC. Citation Format: Avonne E. Connor, Richard N. Baumgartner, Stephanie D. Boone, Christina M. Pinkston, Kathy B. Baumgartner. Risk of second primary cancer (SPC) after breast cancer: A pooled analysis of Hispanic and non-Hispanic white women from New Mexico. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C87. doi:10.1158/1538-7755.DISP13-C87