Ella Binational Breast Cancer Study Research Articles

Circulating soluble levels of MIF in women with breast cancer in the molecular subtypes: relationship with Th17 cytokine profile.

Breast cancer (BC) is a health problem worldwide; there is evidence that inflammatory cytokines are increased in BC. Macrophage migration inhibitory factor (MIF) has multiple effects on immune cells, inflammation and cancer. Besides, in previous studies, contradictory and uncertain results have been presented on the implication of Th17 cytokine profile in BC. The aim of this study was to evaluate the plasma levels of MIF and the Th17 cytokine profile in BC and their association with their molecular subtypes and clinical stage. A total of 150 women with BC of Ella Binational Breast Cancer Study and 60 healthy women (HW) were evaluated in cross-sectional study. The molecular subtypes were identified by immunohistochemistry. The plasma levels of MIF were quantified by ELISA and Th17 cytokine profile by multiplex system. MIF and IL-17 were significantly increased in BC versus HW (11.1 vs. 5.2ng/mL and 14.8pg/mL vs. 2.5pg/mL p < 0.001, respectively). Our analysis showed that both MIF and IL-17A were associated with increased risk of breast cancer (OR 3.85 CI 95% 1.98-7.50 and OR 4.51 95% 1.83-11.15, respectively), higher in aggressive subtypes Luminal B, HER2 and TN. Likewise, we observed positive correlation between MIF and IL-17A (p < 0.001). In addition, IL-17E was lower in BC versus HW (p <0.001). Likewise, we observed a positive correlation between MIF and IL-17A (p < 0.001). In conclusion, both MIF and IL-17A were associated with high risk for breast cancer and aggressive molecular subtypes.

Impact of acculturation on breast cancer treatment and survivorship care among Mexican American patients in Texas.

Given the increasing number and diversity of cancer survivors in the USA and persistent racial/ethnic disparities in breast cancer care, we sought to examine the role of acculturation in adherence to recommended surgical treatment and survivorship care recommendations. Study participants included 343 Mexican American women with stage I to III breast cancer who participated in the Ella Binational Breast Cancer Study and were treated at The University of Texas MD Anderson Cancer Center in Houston, Texas, between March 2007 and June 2011. Participants completed a questionnaire measuring acculturation, and clinical and demographic variables were obtained from an institutional database. Multivariable logistic regression models were constructed to examine differences in surgical procedures received and adherence to long-term survivorship care by acculturation level. Bilingual (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 0.85-4.02, P = .11) and English-dominant women (OR = 2.39; 95% CI = 1.02-5.61, P = .04) were more likely to receive breast-conserving surgery (versus mastectomy) than were Spanish-dominant women. Among all patients, adherence to surveillance mammography and clinic visits decreased over time; the decline in clinic visit adherence was statistically significant (P = .005). Although no statistically significant association was found between acculturation and adherence to long-term survivorship care, receipt of breast-conserving surgery (versus mastectomy) was significantly associated with higher adherence to surveillance mammograms. Acculturation may play a role in decision-making about surgical management of breast cancer, and further studies with larger samples are needed to explore its role in adherence to survivorship care recommendations. Findings from this study may help identify patients requiring additional support while making decisions pertaining to their cancer treatment and survivorship care.

Abstract B17: Family history of breast and ovarian cancer prevalence and its association with triple-negative subtype in Hispanic women

Abstract Background: A family history of breast cancer in a first-degree relative is an established risk factor for breast cancer; however, little is known about the profile of breast and ovarian family history in Hispanic/Latina women. Importance of this relates to recent reports showing a high prevalence of BRCA mutations in Hispanic/Latina women and a pattern of multiple recurrent mutations. In addition, less is known about the association of family history and tumor subtype in this growing ethnic group in the U.S. Methods: Study participants included breast cancer patients of Mexican descent enrolled in the Ella Binational Breast Cancer Study. We first assessed the self-reported breast and ovarian family history profile in 1,150 women. Second, we compared differences in family history of breast and ovarian cancer prevalence between triple negative breast cancer (TNBC) and non-TNBC in 914 patients with available tumor subtype data. Logistic regression was conducted to compare odds of TNBC to non-TNBC according to family history of breast and ovarian cancer. Results: Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively. A history of breast or ovarian cancer in first-degree relatives was reported in 14.9% of the women. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC compared to non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC was 1.93 (95% CI, 1.26–2.97) for women with first-degree relatives with breast or ovarian cancer. There was a suggestion of stronger associations between family history and TNBC among women diagnosed at age &amp;lt;50 compared to those &amp;gt;50 years for breast cancer history in first-degree (P-interaction=0.14) and first- or second-degree relatives (P-interaction=0.07). Conclusion: Findings suggest that familial cancers are associated with triple negative subtype, possibly related to the prevalence of BRCA mutations in Hispanic women, which are strongly associated with TNBC. Improvement in collection of family history through new tools and instruments targeting English- and Spanish-speaking Hispanic women should be a priority for future research. Identification of a strong family history can ultimately affect treatment plans, screening practices, and prevention options both for patients and their relatives. Citation Format: Maria Elena Martinez, Kristin Anderson, Patricia Thompson, Betsy C. Wertheim, Lorena Martin, Ian Komenaka, Melissa Bondy, Adrian Daneri-Navarro, Maria Mercedes Meza-Montenegro, Luis Enrique Gutierrez-Millan, Abenaa Brewster, Lisa Madlensky, Malaika Tobias, Loki Natarajan. Family history of breast and ovarian cancer prevalence and its association with triple-negative subtype in Hispanic women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B17.

Abstract C74: Epigenetic changes in postpartum breast cancer amongst Hispanic women

Abstract The risk of breast cancer has been shown to increase immediately following pregnancy. Breast cancers that occur in the post-partum period are more aggressive, more likely to metastasize and are associated with worse patient outcomes. They also tend to affect younger women, and may represent a substantial proportion of early onset breast cancer, a phenomenon that disproportionately affects racial and ethnic minority groups, such as Hispanics. Hispanic women are more likely to have higher parity, are diagnosed with breast cancer at a younger age, and have a worse survival after diagnosis. The goal of this study, therefore, is to compare breast cancers diagnosed in Hispanic women in the high-risk post-partum period with those diagnosed outside of this time period to identify epigenetic features associated with the aggressive post-partum cancer. RNA and DNA were isolated from formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues from a Hispanic population within the Ella Binational Breast Cancer study participants. Using a quantitative real-time reverse transcriptase approach (Exiqon miRCURY LNA™ Universal RT microRNA PCR panels), we were able to test for the expression of 360 human microRNAs (miRNAs) that our laboratory previously identified as miRNAs that are specific for human mammary cells. MiRNAs are short-stranded, non-coding RNAs that are often deregulated in breast cancer. We have identified seven miRNAs that are differentially expressed in breast cancer that occurs in the post-partum period including: hsa-miR-137, hsa-miR-31, hsa-miR-342-3p, hsa-miR-342-5p, hsa-miR-542-5p, hsa-miR-190b, and hsa-miR-103. Previously, our laboratory showed that epigenetic modifications, such as DNA methylation, deregulate miRNA expression in breast cancer. Consequently, we used a Sequenom MassARRAY platform to determine whether these miRNAs are also being epigenetically regulated. We are also investigating the mechanistic role these miRNAs may play in the early onset post-partum breast cancers. Citation Format: Jose L. Munoz-Rodriguez, Lukas Vrba, Chengcheng Hu, Patricia A. Thompson-Carino, Maria Elena Martinez, Bernard W. Futscher. Epigenetic changes in postpartum breast cancer amongst Hispanic women. [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 C74. doi:10.1158/1538-7755.DISP13-C74

Reproductive and Hormonal Risk Profile According to Language Acculturation and Country of Residence in theEllaBinational Breast Cancer Study

We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent. To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors. After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21). Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.

Abstract P3-07-05: Frequent BRCA1 and BRCA2 mutations are found in Mexican and Mexican-American women with breast cancer

Abstract Background: The Arizona Cancer Registry has shown that in Pima County, AZ, breast cancer diagnosed in young Latinas increased 40% from 2004-2008, compared to 1999-2003, and Latinas more likely to die of their cancer. This study seeks to characterize genetic variation in women of Mexican ancestry with breast cancer using next generation sequencing, with the goal of providing prevalence information to help guide screening and cancer prevention efforts. Methods: The ELLA Binational Breast Cancer Study enrolled women of Mexican ancestry living in either U.S. or Mexico within 24 months of breast cancer diagnosis. Mexican women from the state of Jalisco were collected through collaboration with the Universidad de Guadalajara and women of Mexican ancestry were recruited from Tucson and Phoenix, AZ. Genomic DNA from 92 ELLA study participants (49 from the U.S. and 43 from Mexico) was enriched for breast cancer influencing gene sequence using the BROCA panel with standard techniques. Samples were sequenced with next generation sequencing and variants identified. Results: Sequencing of breast cancer risk genes in 92 Mexican and Mexican-American women with breast cancer revealed the presence of deleterious mutations in 15% of women (14/92). Five carry mutations in BRCA1, 5 in BRCA2, 2 in CHEK2, 1 in PALB2 and 1 in RAD51C. An additional 9% of participants (8/92) carry rare mutations of unknown functional consequence in the same genes. Four carry mutations in BRCA1 or BRCA2 at sites predicted to alter splice enhancers and four carry missense mutations in CHEK2 that are predicted to damage to kinase function. None of these variants appear in public databases or are characterized functionally in gene-specific databases. Dozens of women carry VUS or novel variants. Women carrying BRCA1 mutations are significantly more likely to have had triple negative pathology. Women carrying other mutations known or thought to be deleterious are also more likely to have been younger at diagnosis, to have more aggressive breast cancer or to report a family history of breast cancer. Table 1. Deleterious MutationsGeneEffectTotalBRCA1185delAG1BRCA12569delC2BRCA1Del Complete Gene1BRCA1Del Exons 9-121BRCA2c.658delGT1BRCA2c.3264insT2BRCA2c.5195delT1BRCA2c.6024insG1CHEK2R160G2PALB2S779 Stop1RAD51CDel Exons 4-91 Conclusion: Deleterious BRCA1 and BRCA2 gene mutations are common among women of Mexican ancestry diagnosed with breast cancer. Within this cohort, the prevalence of BRCA1/2 mutations is 11%, and 4% of women carry mutations in other genes increasing breast cancer risk. This is higher than the 10% mutation prevalence estimated for Ashkenazi Jewish women with breast cancer. An additional 9% of women carry variants likely to disrupt gene function and dozens of VUS and novel variants are found in these women. Further analysis of samples from the remaining 942 women using genetic sequencing will help further elucidate the role of genetic risk factors in women of Mexican ancestry with breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-05.

Abstract B119: Presence of etiologic heterogeneity by breast tumor subtypes in Hispanic women with unique reproductive risk factor patterns

Abstract Background: Published data support the presence of etiologic heterogeneity by breast tumor subtype, but few studies have assessed this in Hispanic populations. Methods: We assessed tumor subtype prevalence and associations between reproductive factors and tumor subtypes in 1041 women of Mexican descent (559 U.S. and 482 Mexico) who participated in the Ella Binational Breast Cancer Study. Multinomial logistic regression comparing human epidermal growth factor receptor 2 positive tumors (HER2+, regardless of ER or PR status) and triple negative breast cancer (TNBC) to hormone receptor positive (HR+) tumors was conducted. Results: A higher proportion of ER- tumors was shown for women in Mexico (40.5%) vs. those in the U.S. (27.2%) and slightly higher proportions of HR+ (61.2% vs. 57.9%) and HER2+ (23.8% vs. 20.3%) tumors were observed in the U.S. compared to Mexico. Prevalence of TNBC was 16.7% overall; the percentage was higher for Mexican vs. U.S. women (19.5% vs. 14.5%). After adjustment for age and country of residence, compared to women with HR+ tumors, those with a later age at first pregnancy were significantly less likely to have TNBC (odds ratio [OR]=0.61; 95% confidence interval [CI]=0.39-0.95), whereas those with ≥ 3 full-term pregnancies were significantly more likely to have TNBC (OR=1.68; 95% CI=1.10-2.55). Patients who reported breastfeeding for &amp;gt;12 months were over twice as likely to have TNBC than HR+ tumors (OR=2.14; 95% CI=1.24–3.68). A lower odds of TNBC was shown for longer menstruation duration, whether prior to first pregnancy (OR=0.78; 95% CI= 0.65–0.93 per 10 years) or prior to menopause (OR=0.79; 95% CI, 0.69–0.91 per 10 years). Associations comparing HER2+ to HR+ tumors were weak or non-existent except for the interval between last full-term pregnancy and breast cancer diagnosis. Conclusions: Findings show etiologic heterogeneity by tumor subtype in a population of Hispanic women with a unique reproductive profile. Given that Hispanic women have higher risk of breast cancer-specific mortality than non-Hispanic whites, our findings add to growing evidence of opposing effects of reproductive factors on breast tumor subtypes, which may partly explain disparities in outcomes. Citation Format: Maria Elena Martinez, Betsy Wertheim, Loki Natarajan, Richard Schwab, Melissa Bondy, Adrian Daneri-Navarro, Maria Mercedes Meza-Montenegro, Luis Enrique Gutierrez-Millan, Abenaa Brewster, Ian K. Komenaka, Patricia A. Thompson. Presence of etiologic heterogeneity by breast tumor subtypes in Hispanic women with unique reproductive risk factor patterns. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B119.

Abstract B34: Pregnancy-associated breast cancer and differentially expressed microRNAs.

Abstract MicroRNAs (miRNAs) are short-stranded, non-coding RNAs that regulate gene expression. The expression of miRNAs is often deregulated in breast cancer. Epigenetic modifications, such as DNA methylation, have been shown to regulate miRNA gene expression in breast cancer. In our study, we set out to analyze the role that differentially expressed miRNAs play in pregnancy associated breast cancer (PABC) amongst a Hispanic population within the Ella Binational Breast Cancer study. PABC is defined as cancer that arises within a time-frame of 10 years after pregnancy. Previous studies have shown that women diagnosed with PABC do far worse than women diagnosed with non-PABC. Our hypothesis is that the epigenetic regulation of miRNA genes contributes to poor survival in PABC. We are testing our hypothesis using a cohort of post-partum formalin fixed, paraffin embedded (FFPE) breast cancer tissues from a Hispanic population. Using Exiqon miRCURY LNA™ Universal RT microRNA PCR panels we were able to test for the expression of 360 human miRNAs, which our laboratory previously identified as miRNAs that are specific for human mammary cells. Preliminary data from a small subset of samples showed six miRNAs that were differentially expressed (having &amp;gt; 4-fold expression and a p-value ≤ 0.05) between PABC and non-PABC (hsa-miR-876-5p; hsa-miR-299-3p; hsa-miR-137; hsa-miR-187; hsa-miR-873; hsa-miR-190b ). Several of these miRNAs have been implicated in carcinogenesis. Our goals are to identify differentially expressed miRNAs and to determine the extent of the epigenetic regulation of those miRNAs. These miRNAs will be evaluated for their potential utility as targets of epigenetic regulation and targets for therapeutic interventions. In addition, our studies will be the first to look at epigenetic mechanisms related to PABC in Hispanics. Hispanics have one of the highest fertility rates and an early breast cancer diagnosis. Therefore, our results will elucidate factors associated with this PABC disparity. Citation Format: Jose Luis Munoz-Rodriguez, Lukas Vrba, Patricia A. Thompson-Carino, Maria Elena Martinez, Bernard W. Futscher. Pregnancy-associated breast cancer and differentially expressed microRNAs. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B34.

Association Between Parity and Obesity in Mexican and Mexican–American Women: Findings from the Ella Binational Breast Cancer Study

Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI)≥30kg/m(2), waist circumference (WC)≥35 in (88cm), and waist-to-hip-ratio (WHR)≥0.85. Prevalence of obesity ([BMI]≥30kg/m(2)) was 38.9%. For WC, the multivariate odds ratio (OR) (95% confidence interval [CI]) for having WC≥35 inches in women with≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR=1.10; 95% CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.

Abstract A80: Parity and obesity in Mexican and Mexican-American women: Findings from the Ella Binational Breast Cancer Study

Abstract Background: Obesity rates are increasing rapidly around the globe. Obesity is associated with negative health consequences including increased risk of all-cause mortality and increased breast cancer morbidity. In the U.S., some of the highest rates of obesity are found among Hispanic women. Additionally, factors associated with low socioeconomic status have also been shown to be positively associated with obesity in the U.S., independent of race or ethnicity; higher parity (i.e., three or more full-term births) has also been implicated as a contributing factor. The aim of this study was to evaluate the independent contribution of parity on obesity in a highly parous population of Mexican and Mexican-American women diagnosed with breast cancer. Methods: Participants are from the Ella Binational Breast Cancer Study, a study of women of Mexican descent who were 18 years of age and older at time of enrollment and who were diagnosed with invasive breast cancer within 24 months of recruitment. Each participant completed an interviewer-administered risk factor questionnaire, provided a blood or saliva sample, and consented to provide tumor tissue and access to medical record data. Obesity was defined as having a body mass index (BMI) ≥30 kg/m2, which was calculated from self-reported height and weight. Parity was defined as the number of full-term live births. Age at interview, age at first full-term pregnancy, level of education, employment, smoking status, menopausal status, age at menarche, and breastfeeding were assessed as potential confounding factors. Among U.S. participants, level of acculturation, interview language and nativity were also evaluated as confounders. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multinomial logistic regression. Results: Mean age was higher for U.S. compared to Mexican participants (54.4 ± 12.6 vs. 50.1 ± 12.0). Approximately 51% (n=608) of participants resided in Mexico and 49% (n=579) in the U.S. Among U.S. participants, 54% were born in Mexico and of these, 42% have lived in the U.S. &amp;lt; 10 years. A higher proportion of the U.S. than Mexican women were classified as obese (40.8% vs. 34.5%). Parity was slightly higher among Mexican compared to U.S. women (3.9 ± 2.4 vs. 3.1 ± 1.7 births). We observed a positive association between parity and obesity. In the age-adjusted model, using women with 1–2 live births as the referent group, the OR (95% CI) for women with three full-term births was 1.49 (95% CI, 1.09–2.06). For women with four or more births, the OR (95% CI) was 1.40 (1.02–1.91); Ptrend=0.04. The association was attenuated with the inclusion of education in the model (Ptrend=0.15). When stratified by country of residence at the time of interview, the positive association persisted. Conclusions: Our results show a significant, positive association between parity and obesity that was not independent of education. Results of our work suggest that both pre and postnatal periods are important adult life periods for health care providers to implement obesity prevention strategies and interventions. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A80.

Abstract A94: Assessment of Westernization in Mexican women with breast cancer

Abstract Purpose of Study: Until recently, breast cancer (BC) was relatively rare in Mexico; although incidence is less than half of that in the US, it is now the most commonly diagnosed cancer in women. BC is most common in industrialized regions and in the northern parts of Mexico. This study provides validation results for a measure of Westernization, or more specifically, US social, lifestyle and cultural influences among Mexican women with invasive BC. Study participants are a sub-sample of the Ella Binational Breast Cancer Study. The creation and validation of a Westernization instrument is the first step in understanding US influence on lifestyle and reproductive factors that play a key role in BC risk and appear to influence tumor subtype. Experimental Procedures: A 26-item Westernization survey was administered via interview to 341 Mexican women residing in Obregon and Hermosillo Sonora, as well as Guadalajara, Jalisco between 2009 and 2010. The Westernization instrument was developed through focus group and content expert review. The guiding themes included materialism, individualism, modernity, and reproductive and gender-related norms. The instrument contains three subsections with response formats to reflect various beliefs and behaviors consistent with the themes. The instrument was part of a larger BC risk factor questionnaire, which included questions on demographics, socioeconomic status, as well as all major BC risk factors (e.g., parity, breast feeding, family history, obesity, tobacco). Data Summary: Among the respondents, the mean age was 54.4 years (+ 12.6) and 64% had less than the equivalent of a high school education. The mean number of full term pregnancies was 3.9 (+ 2.4) and the mean age at first full term birth was 22.7 years (+ 5.1); 86% reported ever breastfeeding. The mean body mass index (kg/m2) was 28.6 (+ 5.5); 2.0% were current smokers, 27.6% were former smokers, and 70.4% were never smokers; 8.9% reported a positive family history of BC. Psychometric analysis proceeded on each subsection of the instrument separately. The first subsection reflected 11 modernity related behavioral items. An exploratory principal components analysis showed two factors had eigen values significantly (p &amp;lt; .01) larger than those expected in simulation based parallel analysis, while the 3rd and further factors had eigen values significantly smaller than those expected in those simulation analysis (p &amp;gt; .01). Consequently a two-factor solution was determined to be robust and guided sub-scale development. The sub-scale reflected consumerism (e.g., eating fast food frequently, shopping to distract from one's feelings), was maximized at .84 when two lesser items were removed. The sub-scale reflected use of electronic devices, α = .67 when two lesser fitting items were removed. As traditional or gendered sex role responses (2nd subsection) were “yes/no” (I have/will do this), an alternative psychometric approach was done. The adjusted reliability coefficient was .79 for these seven items and removing no items raised this coefficient, suggesting all items should be used in this measure. Next, sub-scale scores were derived and associations were examined, total modernity was significantly negatively associated with traditional gender norms and age. Conclusions: The results show that this new instrument has sound psychometrics in its first two subsections. The instrument may be used as a complimentary measure in sophisticated models of culture which are applied to Mexican and US Mexican immigrants. The next steps in this study will examine the components of Westernization and their relations to known protective and risk factors of BC and tumor sub-types. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A94.

Abstract B19: Reasons for refusal to participate in an epidemiologic study of minority women

Abstract Purpose: It is widely believed that minorities are less willing than non-Hispanic whites to participate in biomedical research studies. However, to our knowledge, there are no data comparing refusal rates between African-Americans and Mexican-Americans. We assessed refusal rates and reasons for non-participation in an epidemiologic study of breast cancer in African-American and Mexican-American women. Methods: The multi-center ELLA Bi-National Breast Cancer Study compares patterns of breast cancer tumor markers between women of Mexican descent in both the United States and Mexico. At the University of Texas MD Anderson Cancer Center (MDACC), both Mexican-American and African-American women are screened and recruited by trained study personnel, and an in-person interview is conducted. For women refusing to participate, demographic and clinical characteristics and reasons for refusal are collected at the time of refusal. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and refusal to participate. The current study uses data only from MDACC. Results: Approximately 1,870 women were screened to determine eligibility. Of those, 914 were eligible, and 850 (93%) of the eligible women agreed to participate. The two most common reasons for refusal were lack of interest and being too overwhelmed with their breast cancer diagnoses, and 10% of the women stated that their families did not approve of their participation. Those refusing to participate were more likely to be African-American (p&amp;lt;0.001), late stage (p=0.01), and older age at diagnosis (p=0.02). Among African-American women, those refusing to participate were older (p=0.02), later stage at diagnosis (p=0.06), and less educated (p=0.06) compared to the participants. There were no significant differences between the Mexican-American participants and refusals. After adjusting for age and stage at diagnosis, African-American women were twice as likely to refuse participation as Mexican-Americans (OR=2.06, 95% CI: 1.11–3.83). Conclusions: Overall, African-American and Mexican-American women were willing to participate in an epidemiologic breast cancer study, and our participation rates were higher than those previously reported for both African-Americans and Hispanics. Studies have shown that participation rates are higher among women and among cases, two factors potentially contributing to our low refusal rates. It is also possible that our study of only minority women led to low refusal rates among African-American and Mexican-American women. However, African-American women were more than twice as likely to refuse participation, and we must identify which factors influence the decision of minority women to participate in medical research studies. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B19.

Abstract PR-5: Risk factor distribution among women of Mexican descent by level of acculturation: Findings from the ELLA Binational Breast Cancer Study

Abstract Purpose of Study: Studies have shown that breast cancer (BC) risk is higher in U.S.-born Hispanics than foreign-born Hispanics and is modified by age at migration, duration of residence in the U.S., and level of acculturation. Furthermore, epidemiological data support the notion of distinct reproductive factor associations for specific BC tumor subtypes. The aim of this study is to assess the association between established BC risk factors and level of acculturation and country of residence among Mexican American (MA) and Mexican BC cases. Experimental Procedures: This case-only study examined the risk factor profile in 606 Mexican and 488 MA (20% US-born and 80% foreign-born) women, with a confirmed diagnosis of invasive BC, who were recruited into the ELLA Binational Breast Cancer Study between March 1,2007, and May 31,2010. Participants completed an interviewer-administered risk factor questionnaire, consented to a medical record review, and provided tissue and saliva or blood specimens. An eight-item language-based Bidimensional Acculturation Scale (BAS) was used to classify MA women as English-dominant (n=88), bilingual (n=221), or Spanish-dominant (n=179). The BAS is highly correlated with nativity and time in the US, however language use/exposure was focal for this study since it is the single strongest predictor of acculturation. Chi-square tests, ANOVA, and regression models to test for trend were used to assess variation in the risk factor profile by level of acculturation. Summary of Results: Age at diagnosis was generally low; the lowest was among MA-bilingual women (48.9 = 12.0 years) and highest among Mexican women (53.7 = 12.7 years). Considering a gradient of increasing acculturation from Mexican (lowest) to MA-English dominant (highest) women, there were clear trends for decreasing rates of breastfeeding (80.2 to 35.2%; p-trend&amp;lt;0.0001); earlier age at menarche (13.0 = 1.5 to 12.2 = 1.5 years; p-trend&amp;lt;0.0001), and lower parity (3.9 = 2.5 to 2.6 = 1.2 live births; p-trend&amp;lt;0.0001). However, for some factors, the data show a dichotomy between Mexican and MA-Spanish dominant women versus MA-bilingual and MA-English dominant women; these include oral contraceptive use (51.7% and 47.2% versus 66.1 % and 62.1 %, respectively); age at natural menopause (48.1 and 48.5 vs. 49.2 and 49.1 years, respectively); and hormone replacement therapy use (11.0% and 9.6% vs. 20.0% and 17.2%, respectively). No clear trends or patterns were evident for recent body mass index (BMI), physical activity, or alcohol consumption. MA-Spanish dominant women had the highest BMI (30.2 = 7.1 kg/m2), MA-English dominant women had the lowest levels of physical activity (650.2 = 1265.1 kcal/day), and MA-bilingual women had the highest proportion of alcohol intake (13.8% consumed ≥1 drink/day). Conclusion: Our results show that heterogeneity in BC risk factor patterns by level of acculturation is present. Given the recent data supporting distinct correlations between specific risk factors and BC subtypes, it will be essential to consider level of acculturation and country of residence when assessing the prevalence of these subtypes. The trends observed in risk factor profiles by level of acculturation in the ELLA Study could provide important explanations for differences in disease patterns between groups. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-5.

Abstract A89: HER2-overexpressing tumors and time since last pregnancy

Abstract Background: Risk of dying from breast cancer is higher among Hispanic women compared to non-Hispanic whites (NHW) despite lower overall incidence rates and a more favorable risk factor profile. Part of the observed disparity can be explained by aggressive tumor biology although unequal access to care is also a key factor. A recent pooled case-only study suggests Hispanic women are more likely to be diagnosed with HER2-positive tumors compared to NHWs. Given the high parity rates among Hispanics and recent interest in the differential effect of reproductive factors on breast tumor subtypes, we investigated the relative correlation between reproductive factors and tumor phenotype stratified on HER2 status. Methods: A total of 459 women of Mexican origin from the case-only ELLA Binational Breast Cancer Study were classified into hormone receptor (HR) positive cases (estrogen or progesterone-receptor positive, HER2-negative) and HER2-overexpressing cases (HER2+, HR-). Women negative for all three markers (triple negative) were not considered in these analyses. Reproductive factors considered in the analysis include age at first full-term pregnancy, total number of full-term pregnancies, ever breastfeeding, breastfeeding after last pregnancy, and time since last pregnancy. Time to diagnosis since last pregnancy was classified as either ≤10 years or &amp;gt;10 years. We conducted separate analyses for women diagnosed at ≤ 40 years (n=72) and at &amp;gt;40 years of age (n=386). Differences were tested using a Pearson chi-square test or Student's t-test. We calculated case-case odds ratios (OR) and 95% confidence intervals (CI) using logistic regression to estimate the relative correlation between time since last pregnancy and HER2+ tumors in reference to HR+ tumors. Models included age at diagnosis, recruitment site, age at first pregnancy, number of pregnancies and breastfeeding. Results: Out of 459 women, 338 (74%) were HR+ and 121 (26%) HER2+. No significant differences were observed in the proportion of HR+ tumors among women ≤ 40 and those &amp;gt; 40 (79% vs. 73%, respectively; p=0.22). HER2+ cases were younger at diagnosis compared to HR+ cases (mean age 51.8 vs. 53.1, respectively; p= 0.30). HER2+ cases were more likely to be diagnosed after the age of 40 compared to HR+ cases (OR 4.37; 95% CI: 1.84,10.40) and were more likely to occur within the 10-year period following the last pregnancy (OR=3.99; 95% CI: 1.95,8.16). No difference was observed for age at first full-term pregnancy (OR 0.99; 95% CI: 0.95,1.03), number of full-term pregnancies (OR 0.95; 95% CI: 0.84,1.07) or ever breastfeeding (OR 0.98; 95% CI: 0.59,1.62). A significant interaction was observed between time since last pregnancy and age at diagnosis (p=0.03). Stratified results suggest the relationship between time since last pregnancy and tumor phenotype is stronger in the &amp;gt;40 age group (OR 3.68; 95% CI: 1.60,8.44) compared to those ≤40 (OR 2.68; 95% CI: 0.19,37.16). Conclusions: HER2+ tumors were more likely to be diagnosed in the 10-year period after the last pregnancy compared to HR+ tumors, independent of age. These findings suggest a relationship between HER2+ breast cancer and pregnancy history that differs from that with HR+ tumors, supporting the presence of etiologic heterogeneity in these subtypes. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A89.

Abstract 2806: Factors that influence screening mammography among African American and Mexican American women with breast cancer: Findings from the ELLA Binational Breast Cancer Study

Abstract Screening mammography is associated with early detection of breast cancer (BC) and reduced BC mortality. To understand factors that influence screening mammography receipt in minority women with unrecognized risk factors for BC, this study examined BC screening behaviors among women with BC. Due to the BC survival disparities observed in African American (AA) and Mexican American (MA) women compared to whites, AA and MA women living in Texas and Arizona who were participants of the ELLA Binational Breast Cancer Study were selected for this study based on a diagnosis of BC. Data on socioeconomic status (SES), reproductive history, family history, insurance status, acculturation, and breast health history were collected via questionnaires and medical record abstraction. 601 women aged 40 years or older at time of BC diagnosis were included in this study, including 270 AA, 151 MA women classified as high-acculturation (MA-HA) and 180 MA women classified as low-acculturation (MA-LA). Logistic regression analysis was used to assess differences in mammography receipt in the last five years prior to BC diagnosis stratified by race/ethnicity and acculturation and for all groups combined. MA women in this study suffer a larger disparity than AA women with regards to screening mammography. Despite high rates of screening mammography among AA and MA women, 62% of BC was self-detected in the study population. AA women (OR=1.0) and MA-HA (OR=0.91; 95% CI: 0.57-1.48) women were more than twice as likely to receive screening mammography compared to MA-LA (OR=0.38; 95% CI: 0.25-0.59), adjusted for age. After adjusting for age, education, and insurance, there was no significant difference in screening mammography receipt between these three groups. Women who had a known family history of BC were more than twice as likely to receive screening mammography than women who had unknown or no family history (OR=2.02; 95% CI: 1.19-3.55). However, although AA and MA-HA women were twice as likely as MA-LA to report a family history of BC (20% vs. 23% vs. 12%, respectively), recognized family history did not account for the differences in screening mammography use between these groups. Thus, the differences observed in screening mammography receipt by race/ethnicity and acculturation among AA, MA-HA, and MA-LA are likely explained by SES variables, including education and insurance. Due to the large proportion of AA and MA women who reported self-detecting their BC, women must be educated about the importance of breast awareness and prompt reporting of findings to a health professional after noticing breast changes. In addition, cancer screening programs targeting underserved women should provide culturally appropriate messages about the importance of knowing their family history and the benefits of screening mammography. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2806.

Comparative study of breast cancer in Mexican and Mexican-American women

Breast cancer is the number one cause of can- cer deaths among Hispanic women in the United States, and in Mexico, it recently became the primary cause of cancer deaths. This malign- nancy represents a poorly understood and un- derstudied disease in Hispanic women. The ELLA Binational Breast Cancer Study was es- tablished in 2006 as a multi-center study to as- sess patterns of breast tumor markers, clinical characteristics, and their risk factors in women of Mexican descent. We describe the design and implementation of the ELLA Study and provide a risk factor comparison between women in the U.S. and those in Mexico based on a sample of 765 patients (364 in the U.S. and 401 in Mexico). Compared to women in Mexico, U.S. women had significantly (p < 0.05) lower parity (3.2 vs. 3.9 mean live births) and breastfeeding rates (57.5% vs. 80.5%), higher use of oral contraceptives (60.7% vs. 50.1%) and hormone replacement therapy (23.3% vs. 7.6%), and higher family history of breast cancer (15.7% vs. 9.0%). Re- sults show that differences in breast cancer risk factor patterns exist between Mexico and U.S. women. We provide lessons learned from the conduct of our study. Binational studies are an important step in understanding disease pat- terns and etiology for women in both countries.

Breast Cancer Probed in Hispanic Women

MOUNTING EVIDENCE SHOWS that Hispanic women appear more likely than white or black women to have hereditary forms of breast cancer, raising important implications for more targeted screening and early cancer detection. “[This] is an issue that affects the United States because of the large and growing population of Hispanics in this country,” said Elena Martinez, PhD, of the University of Arizona’s Mel and Enid Zuckerman College of Public Health in Tucson. Martinez is a co-leader of the 3-yearold ELLA Binational Breast Cancer Study, a collaboration among investigators in the United States and Mexico. Funded by the National Cancer Institute and the Avon Foundation, the initiative aims to determine common types of cancer and specific cancer risk factors in women of Mexican descent. During a press briefing in February at the American Association for Cancer Research (AARC) Conference on the Science of Cancer Health Disparities in Carefree, Ariz, Martinez and other scientists discussed some of the first results released from the ELLA study.