Breast Cancer In African American Women Research Articles

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

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

Genomic profiling of breast cancer in African-American women using MammaPrint

Breast cancer in African-American females (AAF) has a less favorable outcome than that in Caucasians. More information is needed regarding its biology. We evaluated gene expression in tumors from AAF presenting with early stage or locally advanced breast cancer using MammaPrint(®), BluePrint (®) (molecular subtype) and TargetPrint (®) [estrogen receptor (ER), progesterone receptor, and Human Epidermal Growth Factor Receptor 2 (HER2) mRNA levels]. Genomic information was correlated with clinical and pathologic characteristics and Oncotype DX(®) Recurrence Score(®) (RS). One hundred Patients were enrolled, 1 not evaluable by BluePrint. The median age was 60years (range 22-98), and eighty-four (84%) patients had stage I or II disease. High Risk MammaPrint was present in 66% of patients and in 52% of patients with stage I disease. High Risk MammaPrint was associated with young age (p=0.02), high grade (p<0.0001), HER2 expression (p=0.016), and triple-negative phenotype (p<0.001). Sixty-four tumors (65%) were Luminal type (47% of these were classified as High Risk), 26 (26%) were Basal type, and 9 (9%) HER2 type. Twenty-two cancers were triple negative (TN) by IHC and 19 (90%) Basal type. Among the 15 tumors HER2 positive by IHC/FISH, 8 (53%) were HER2 type by BluePrint. Eleven tumors with ER expression of 1-9% were ER negative by TargetPrint and none of these was Luminal type. None of the seven tumors HER2 positive by IHC/FISH but negative by TargetPrint was HER type. RS results were available in 29 patients: two had High Risk both by RS and MammaPrint; eight had intermediate RS, with four High Risk by MammaPrint; 19 had a low RS, with eight High Risk by MammaPrint. AAF with stage I to III breast cancer often present with High Risk disease. Molecular heterogeneity is present within TN, HER2-positive, and ER-positive breast cancer. RS and MammaPrint offer different prognostic information.

Health Care Disparities in Hereditary Ovarian Cancer: Are We Reaching the Underserved Population?

Ovarian cancer is an uncommon but deadly disease. There is no effective screening for the disease, and the majority of women with ovarian cancer present in advanced stage and eventually die from their disease. The majority of families with multiple cases of breast and ovarian cancer are found to carry germline mutations in BRCA1/2. Recent, more sensitive sequencing techniques have shown that nearly 20% of ovarian cancer is associated with germline mutations in cancer susceptibility genes, with approximately 15% accounted for by deleterious mutations in BRCA1/2. Women found to have mutations in BRCA1/2 can be empowered to make decisions on reproduction, cancer prevention, or treatment that may either avoid cancer or prolong survival. Though initial studies suggested that African American (AA) women were significantly less likely than White women to have mutations in BRCA1/2, this has been found to be untrue. Despite this revelation, and the clear importance of BRCA1/2 mutation status to appropriate clinical management, AA women still undergo genetic counseling and testing at much lower rates than do comparable White women. This disparity is not explained by factors such as calculated risk of a mutation, insurance coverage, or previous knowledge of the availability of testing. To date, no effective strategies have been identified that can overcome this disparity. Possible approaches include use of patient navigators, online social media, or EMR-based decision support aids. Funders should support research in this area, as it represents an actionable means to decrease the burden of ovarian and breast cancer in AA women.

Abstract IA19: Elucidating the origins of aggressive breast cancer in African American women

Abstract IA19: Elucidating the origins of aggressive breast cancer in African American women

Abstract 4818: Array-CGH and miRNA expression profiling of triple negative breast cancer in African-American women

Abstract In the African-American (AA) population, an increased incidence and shorter survival rate of triple negative breast cancer (TNBC) has been reported when compared to White women, with their cancer usually diagnosed in more advanced stages and with non-localized disease. The main objective of our study is to identify molecular markers in TNBC in AA patients that may be associated with their observed disparity in incidence and mortality rates. Formalin-fixed paraffin-embedded tumor sections were obtained from 26 and 28 cases of TNBC from AA and Caucasian breast cancer patients, respectively, and analyzed for DNA copy number (Agilent-SurePrint G3 Human CGH Microarray 8×60K) and miRNA expression (Nanostring System) alterations. The cases were obtained with clinically annotated data from the Histopathology Shared Resources at the Lombardi Comprehensive Cancer Center. The miRNA data was directly integrated with the array-CGH data from the same cases. Combinatorial target predicted algorithms in conjunction with functional and pathway annotation enrichment systems were performed to identify predicted target functions. A distinct DNA copy number profile was observed between TNBC of AA and Caucasian cases: the cytobands differentially involved in the AA-TNBC cases were 7p22.3-22.1, 12p13.33-p11.1, 17q25.3 and 17p13.3-p11.2. Common cytobands in both groups were 1q21.1-q44, 8q22.1-q24.3, 16p13.33-p11.1 and 20q11.2-q13.12. An average of 30.5 and 16.8 DNA copy alterations were observed between the AA and Caucasian cases respectively and the miRNA profiling revealed 209 miRNAs differentially expressed between the groups. Unsupervised hierarchical clustering analysis separated the cases by ethnicity (with the exception of 6 cases). Among the miRNAs observed with higher and lower expression levels in the AA cases were miR150-5p, miR4286, miR29b3p and miR1283, miR1253, miR378e, respectively. Ingenuity pathway analysis identified molecular and cellular functions mostly related to cellular development, growth, proliferation and movement, and cell death and survival. Clinical pathological data analysis revealed higher tumor grades and stages in the TNBC of AA women when compared to Caucasians; association of these parameters with the genomic and expression miRNA data is being performed. In conclusion, a distinct DNA copy number and miRNA profile was observed in the AA-TNBC cases when compared to the Caucasians cases of our study. These initial findings will provide the basis for the functional analysis of the identified molecular markers and their potential prognostic and therapeutic impact for this group. In addition to providing a better understanding of the biology of their tumors, these analyses can reveal molecular targets for tailored and ethnic-based clinical trials, which can ultimately lead to the reduction of the observed cancer disparity. Support: FDA U01 FD004319, NIH-NIGMS GM101997 and Susan Komen Foundation. Citation Format: Kenny Regis, Michelle Jaldin, Akanksha Mahajan, Anju Duttargi, Laura Sheahan, Yuriy Gusev, Subha Madhavan, Luciane R. Cavalli. Array-CGH and miRNA expression profiling of triple negative breast cancer in African-American women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4818. doi:10.1158/1538-7445.AM2015-4818

Abstract P4-14-11: National trend in African American women breast cancer research productivity from 1992-2012

Abstract INTRODUCTION: Despite extensive progress in breast cancer prevention, diagnosis and treatment over the past 20 years, African American women suffer disproportionate breast cancer morbidity and mortality. In 1998, breast cancer deaths among African American women were 28% higher than in white women and the five-year survival rate for African American women was 71% compared with 86% for white women. The purpose of this bibliometric study is to assess our national research efforts to combat this racial disparity by analyzing breast cancer research productivity in the United States focusing on African American women from 1992 to 2012. METHODS: This retrospective bibliometric analysis of public data was exempt from Institutional Review Board approval. Articles with "Breast Neoplasm" as a major medical subject heading (MeSH) term published between 1992 and 2012 were identified in the National Library of Medicine MEDLINE database. In addition, articles with "African Continental Ancestry Group" which included African American as a major MeSH term were identified. Country of origin, methodology, journal name, first author specialty and funding sources were recorded. Growth in number of publications was analyzed using linear and nonlinear regression statistical analysis. RESULTS: A total of 113,721 journal articles were identified with "Breast Neoplasm" as a major MeSH term worldwide, of which 34,155 (30.0%) were published from the United States. Among United States publications, 668 (2.0%) were specific to African ancestral populations. From 1992 to 2012, both African ancestral and non-African ancestral specific articles displayed linear growth patterns (p &amp;lt; 0.0001). National Institute of Health (NIH) funded studies displayed an exponential growth pattern (p &amp;lt; 0.0001) for African ancestral specific articles and displayed a linear growth pattern (p &amp;lt; 0.0001) for non-African ancestral articles. The largest specialty contributor of African ancestral specific articles was Epidemiology and Public Health (33.2%), followed by Medicine (internal medicine, family medicine, obstetrics &amp; gynecology, nursing) (24.7%), Basic Sciences (17.4%), Surgery (15%), Medical and Radiation Oncology (4.7%), Pathology (2.9%) and Radiology (2.1%). African ancestral specific articles were most frequently published in Cancer (10.8%). CONCLUSION: Among breast cancer publications from the United States, only 2% of the articles were specific to African ancestral population, which is concerning given recent data indicating the persistent ethnic disparity in survival. However, the trend in research productivity in this population is encouraging, largely due to the exponential growth of NIH-funded studies specific for African American women in the past 20 years. NIH-funded research accounts for 52% of all published African American specific breast cancer studies as compared to 40.5% of studies that are non-specific to this population. Ultimately, improvements in breast cancer incidence, mortality, and survival rates in African American women will undoubtedly result from quality research and should continue to be a priority in our nation’s breast cancer research agenda. Citation Format: Ralph T Wynn, Daniel S Chow, Victoria L Mango, Lauren C Friedlander, Richard Ha. National trend in African American women breast cancer research productivity from 1992-2012 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-14-11.

Triple-negative breast cancer in African-American women: disparities versus biology.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. There is evidence that African-American women with TNBC have worse clinical outcomes than women of European descent. However, it is unclear whether survival differences persist after adjusting for disparities in access to health-care treatment, co-morbid disease and income. It remains controversial whether TNBC in African-American women is a molecularly distinct disease or whether African-American women have a higher incidence of aggressive biology driven by disparities: there is evidence in support of both. Understanding the relative contributions of biology and disparities is essential for improving the poor survival rate of African-American women with TNBC.

A prospective study of physical activity and breast cancer incidence in African-American women.

Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited. With prospective data from the Black Women's Health Study, we assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor-positive (ER(+), n = 688) cancer, and estrogen receptor-negative (ER(-), n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI). Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to <1 h/wk was 0.74 (95% CI, 0.57-0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence. High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women. These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women.

Abstract LB-292: Race-associated gene expression in tumors and breast cancer mortality disparities

Abstract Background: African American (AA) women have lower incidence, but higher mortality rates when they are diagnosed with breast cancer. Biological differences in tumor subtypes, with greater prevalence of aggressive basal-like breast cancers in AA women, explain some disparities; however, even when AA women are diagnosed with ‘good prognosis’ Luminal A breast cancers, they fare worse than Caucasian (Cau) women with the same subtype. Our goal was to identify disparity-associated gene expression in breast tumors overall, and in Luminal A breast cancers specifically. Methods: Disparity-associated gene expression was defined as gene expression that was both strongly associated with patient race and with substantial differential in disease-free survival in Cau, defined as the hazard ratio (HR) &amp;gt; 1.25 or &amp;lt; 0.8 comparing patients with &amp;gt;= median expression to those with &amp;lt; median expression. We used microarray data from 165 breast tumor samples (108 Cau and 57 AA women). This dataset included 68 Luminal A tumors and 39 Basal-like tumors. We identified race-associated gene expression using linear models with a false discovery rate (FDR) less than 5%. Genes that were differentially expressed by race in breast cancers overall or among luminal A tumors were tested for associations with survival. Genes that were both race- and survival-associated were further evaluated for race-related patterns of expression in normal reduction mammoplasty samples (N=100) and cancer-adjacent histologically normal (N=92) tissue. Results: At an FDR = 5%, 10 genes were differentially expressed by race in Luminal A tumors. Six of these showed associations with survival [CRYBB2 (HR = 1.36), PSPH (HR = 1.65), ACOX2 (HR = 0.65), MUC1 (HR = 0.65), TYMS (HR = 2.67), SQLE (HR = 1.98)] in NKI295. Two distinct patterns emerged for the expression of these genes in normal tissue: CRYBB2 and PSPH were differentially expressed in tumor and normal tissue of AA compared to Cau women; ACOX2, MUC1, TYMS, SQLE were only differentially expressed in tumors. A composite expression score based on expression of all six genes, or including only CRYBB2/PSPH, was associated with tumor characteristics. Furthermore, composite expression was associated with survival across all tumors and Luminal A tumors in an independent dataset. Discussion: These analyses replicated previously reported associations between CRYBB2 and PSPH expression in breast tumors and race, and extended the analysis to address normal tissue differences and survival among Luminal A tumors. These patterns in normal tissue suggest that CRYBB2 and PSPH expression could represent race-specific differences in susceptibility to aggressive tumors. Although disparities in luminal A breast cancer mortality may be related to treatment or access to care, these data suggest that biological differences between at-risk AA and Cau women may also be operating. Citation Format: Monica E. D’Arcy, Whitney R. Robinson, Erin Kirk, Keith D. Amos, Charles M. Perou, Jodie M. Fleming, Melissa A. Troester. Race-associated gene expression in tumors and breast cancer mortality disparities. [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 LB-292. doi:10.1158/1538-7445.AM2014-LB-292

Parity, Lactation, and Breast Cancer Subtypes in African American Women: Results from the AMBER Consortium

African American (AA) women have a disproportionately high incidence of estrogen receptor-negative (ER-) breast cancer, a subtype with a largely unexplained etiology. Because childbearing patterns also differ by race/ethnicity, with higher parity and a lower prevalence of lactation in AA women, we investigated the relation of parity and lactation to risk of specific breast cancer subtypes. Questionnaire data from two cohort and two case-control studies of breast cancer in AA women were combined and harmonized. Case patients were classified as ER+ (n = 2446), ER- (n = 1252), or triple negative (ER-, PR-, HER2-; n = 567) based on pathology data; there were 14180 control patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in polytomous logistic regression analysis with adjustment for study, age, reproductive and other risk factors. ORs for parity relative to nulliparity was 0.92 (95% CI = 0.81 to 1.03) for ER+, 1.33 (95% CI = 1.11 to 1.59) for ER-, and 1.37 (95% CI = 1.06 to 1.70) for triple-negative breast cancer. Lactation was associated with a reduced risk of ER- (OR = 0.81, 95% CI = 0.69 to 0.95) but not ER+ cancer. ER- cancer risk increased with each additional birth in women who had not breastfed, with an OR of 1.68 (95% CI = 1.15 to 2.44) for 4 or more births relative to one birth with lactation. The findings suggest that parous women who have not breastfed are at increased risk of ER- and triple-negative breast cancer. Promotion of lactation may be an effective tool for reducing occurrence of the subtypes that contribute disproportionately to breast cancer mortality.

A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium

Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER- tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER- breast cancer, and the subset of ER- cancers that are basal-like, is about twice as high among African American (AA) women as among US women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women. We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the African American Breast Cancer Epidemiology and Risk consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of genome-wide association studies loci and candidate pathways. To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period. The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic, in relation to specific subtypes of breast cancer in AA women.

Abstract P5-12-07: Triple-negative breast cancer in African American women - How women in New Orleans compare to the rest of Louisiana and the Nation

Abstract Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA) and the US. Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available prior to 2010. We explored the association of HER2 status with age, race, ER, PR, T, N and M status to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. With the recent release of SEER 18 data including HER2 status in cases diagnosed in 2010 we also looked at national rates of Tneg BC in WW compared to AAW and compared these findings to NO and LA. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 34.0 per 100,000 in NO, 27.2 per 100,000 in AAW in the rest of LA and 20.4 per 100,000 in SEER 18. This translates into a statistically significant increase in incidence rates of Tneg BC in AAW in NO by 67% (p = &amp;lt; 0.05) compared to SEER 18. The rates in WW were 11.3 per 100,000 in all 3 locations. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA and locations of the SEER 18 registries. Table 1: 2010 Tneg rates per 100,000 in NO, LA and SEER 18 RateCountRate RatioRate Lower CIRate Upper CIWhiteSEER 1811.33884154 LA11.30512000.99700.85731.1543 NO11.2441320.99160.66501.4340BlackSEER 1820.39961094 LA27.18622041.33271.13841.5534 NO34.0092611.66721.25822.1711 Conclusions: The incidence rates of Tneg BC in AAW in NO and LA are significantly higher than in SEER 18, with rates in NO being the highest. Rates of Tneg BC in WW in all data sets were similar. SEER 18 analysis also confirms a higher incidence of Tneg BC in AAW compared with WW as previously reported in smaller case series. AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-07.

African-American Breast Cancer Survivors Participating in a Breast Cancer Support Group: Translating Research into Practice

Despite an overall decline in mortality, breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer death among African-American women. As such, clinicians should prepare to address the unique sociocultural and psychological concerns encountered by African-American women breast cancer survivors. The objective of this study is to examine, using qualitative methods, the main coping facilitators used by African-American women as they transition across the cancer continuum. The identification of these facilitators was then aligned with culturally sensitive interventions most useful with women coping with cancer along the cancer continuum. This was a secondary analysis of 20 videotaped stories of African-American breast cancer survivors collected as a part of the Washington University Center for Excellence in Cancer Communications project. The interview began with a discussion of how the survivor first became aware she had breast cancer, followed by a series of open-ended probes used to explore the following themes: coping, relationships, health care system experiences, follow-up care, and quality of life living with breast cancer. Survivors discussed their experiences and advice for targeting needs at each cancer stage from screening to diagnosis, treatment, and then survivorship. Survivor narratives point to key evidence-based clinical intervention strategies at each stage of the cancer trajectory. This study found that survivors see a cyclical cancer course, whereby African-American breast cancer survivors serve an important role in the lives of unscreened women, newly diagnosed women, and women in treatment.

Triple negative breast cancer in African American women: Disparity between women in New Orleans versus Louisiana.

e12501 Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA). Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available for prior to 2010 diagnosis. We explored the association of HER2 status with age, race, ER, PR, HER2, T, N, M to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 30 per 100,000 in NO, which was 24% higher than that in AAW in the rest of LA and two-fold the rate in WW of both NO and LA. The highest rate of Tneg BC was seen in AAW aged 65-69 in NO (184.97 per 100,000) compared with 81.5 per 100,000 in AAW aged 55-59 in LA. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA (OR=1.4; 95% CI: 1.01-1.87). Conclusions: AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This disparity remains when comparing our data to previously published literature in other parts of the US. We plan to continue our data analysis and compare NO data to the national average as the HER2 data become available in the SEER Program to better characterize the disparity. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.

Genomic profiling of breast cancer in African-American women.

11054 Background: Molecular profiling of breast cancer (BC) identifies intrinsic subtypes with distinct gene expression and clinical characteristics. In the US, BC is less frequent in African-American females (AAF); however mortality is higher, particularly among younger women. Unfavorable subtypes of BC seem to be more frequent in premenopausal AAF. Methods: Tumor gene expression in AAF presenting with early stage or locally advanced BC was performed using the Symphony platform on fresh and paraffin-embedded tissue (Agendia inc), a microarray-based method which classifies tumors according to prognosis (MammaPrint, MP), molecular subtype (BluePrint, BP) and estrogen receptor (ER), progesterone receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) mRNA levels (TargetPrint, TP). Genomic information is correlated with clinical and pathologic characteristics and Oncotype DX recurrence score (RS) when available. We plan to enroll 100 patients. Results: Results available in 46 patients. Median age 62 years (range 24-100), 20 stage I, 15 stage II, 11 stage III disease. There was no significant association between MP risk and stage, but MP risk was significantly associated with grade 3 disease (p=.006). 9 cancers were triple negative by IHC; using BP, 8 of these were Basal-type and 1 HER2-type. Basal-type was the most common subtype in patients ≤ 40 years old (p &lt; .001). In the 6 cases ER positive by IHC but negative by TP, 3 were Basal-type and 3 were HER2-type.14 patients had Oncotype RS results available: 2 were High Risk by Oncotype and MP; 3 had intermediate RS, 2 of which were High Risk by MP; 9 had a low RS, 4 of which were High Risk by MP. Conclusions: African-American women with stage I to III BC often present with High-Risk disease irrespective of stage. BP classified all young patients (≤40) as Basal-type. Molecular subtyping confirmed the biologic heterogeneity in triple negative and hormone positive tumors. Oncotype RS and MP offered different prognostic information. Follow up will be needed to determine correlation with outcome. Funding: MP, BP and TP test provided by Agendia. Biostatistical support by GHUTTCS-CTSA. [Table: see text]

Invasive breast carcinomas in Ghana: high frequency of high grade, basal-like histology and high EZH2 expression

Breast cancer in African-American women has a worse outcome than in Caucasian women. The ancestors of most African-American women come from West Africa, including Ghana. The Polycomb group protein EZH2 is a marker of poor outcome in breast cancers from Caucasian women. The histopathological features and biomarker expression of African breast cancers remain obscure. Here, we investigated a cohort of Ghanaian breast cancers to better define the prevalent tumor types and to test if EZH2 protein may identify aggressive tumors. A group of 169 breast tissues (100 invasive carcinomas and 69 benign) from women treated at Komfo Anoyke Teaching Hospital between 2006 and 2011 were histologically classified and investigated for EZH2 expression. EZH2 nuclear expression we defined as high or low following previously published criteria. Of the 100 invasive carcinomas, 89 % were ductal, 2 % were lobular, and 9 % were metaplastic. Basal-like pathological features were present in 30 % of the tumors. Of the invasive carcinomas, 7 % were grade 1, 41 % grade 2, and 52 % grade 3. EZH2 protein was overexpressed in invasive carcinomas compared to benign breast (p < 0.0001). In invasive carcinomas nuclear EZH2 overexpression was significantly associated with basal-like subtype (p = 0.03) and high histologic grade (p < 0.05). Cytoplasmic EZH2, which has not been previously reported, was present in 16 % of invasive carcinomas and it was associated with triple negative status (p = 0.02). Our results provide the first comprehensive histopathological study of this patient population and uncover the association of EZH2 with high grade and basal-like tumors. We provide the basis for further detailed investigations on this cohort to advance diagnosis and treatment of African and African-American women.

CAG Repeat Variants in the POLG1 Gene Encoding mtDNA Polymerase-Gamma and Risk of Breast Cancer in African-American Women

The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49–6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies.

The Unmet Needs of African American Women with Breast Cancer

Breast cancer is the most common cancer in women and treatment includes various combinations of surgery, chemotherapy, and/or hormone therapy. The multimodal treatment of breast cancer improves survival outcomes, but it also contributes to a prolonged period of medical intervention with associated physical and emotional consequences. However, we know less about the specific clinical experiences of African American (AA) women during treatment for breast cancer and in survivorship. The studies that have addressed the issue of breast cancer in AA women have focused primarily on early detection and epidemiological variables such a screening, mortality and staging at diagnosis. In our study, in-depth semi-structured phone interviews were conducted to explore the clinical experiences, concerns and needs of AA women who had survived breast cancer. The AA women reported that their physicians did not provide adequate disease and treatment information; did not discuss clinical trials with them; and did not offer access to support services.

The role of anthropometric and nutritional factors on breast cancer risk in African-American women

While the role of nutrition, physical activity and body size on breast cancer risk has been extensively investigated, most of these studies were conducted in Caucasian populations. However, there are well-known differences in tumour biology and the prevalence of these factors between African-American and Caucasian women. The objective of the present paper was to conduct a review of the role of dietary factors, anthropometry and physical activity on breast cancer risk in African-American women. Twenty-six research articles that presented risk estimates on these factors in African-American women and five articles involving non-US black women were included in the current review. Racial disparities in the impact of anthropometric and nutritional factors on breast cancer risk. African-American and non-US black women. Based on the few studies that presented findings in African-American women, an inverse association with physical activity was found for pre- and postmenopausal African-American women, while the association for anthropometric and other dietary factors, such as alcohol, was unclear. Studies assessing the effect by molecular subtypes in African-American women were too few and based on sample sizes too small to provide definitive conclusions. The effect of certain nutrition and lifestyle factors on breast cancer in African-American women is not starkly distinct from those observed in white women. However, there is an enormous need for further research on this minority group to obtain more confirmatory findings.

Abstract B92: The interaction of parity with genetic factors in relation to breast cancer incidence in African American women

Abstract We recently reported a differential association of parity with breast cancer incidence according to hormone receptor status among African American (AA) women, with higher parity associated with a reduced risk of estrogen receptor positive (ER+)/ progesterone receptor positive (PR+) breast cancer and an increased risk of ER−/PR− breast cancer. To elucidate mechanisms for the difference by breast cancer subtype, we examined interactions of parity status with specified genetic polymorphisms that have been identified as breast cancer loci in genome-wide association studies (GWAS). SNPs in three loci were assessed: intron 2 in the FGFR2 gene, which was the most strongly associated of all breast cancer GWAS loci and appears to be most important for ER+ breast cancer; the chromosome 5p12 region, which may also be restricted to ER+ cancer and was replicated in our study of AA women; and the TOX3/LOC643714 locus, which was also replicated in our study. We analyzed data from the Black Women's Health Study, a prospective follow-up study of 59,000 AA women from across the US who enrolled in 1995 and have been followed since then by biennial questionnaires. Incident breast cancer cases are confirmed and characterized as to ER/PR status by review of pathology data. Saliva samples were provided by approximately 27,000 participants through the mouthwash-swish method. Genotyping was conducted on the Sequenom Mass-Array iPLEX technology as part of a project to test index SNPs from European ancestry GWAS as well as other tagSNPs in each region. An average reproducibility of 99% was obtained among blinded duplicates; all SNPs with calling rate &amp;lt;90% and all samples with calling rate &amp;lt;80% were excluded. Mean call rate in the final data set for both SNPs and samples was 99.0%. Genotyping results and questionnaire data on parity and other established risk factors were available for 650 incident breast cancer cases and 1770 controls matched on year of birth and region of residence. Odds ratios for the joint association of genotype and parity and for the association of parity with breast cancer within genotype were carried out by logistic regression controlling for age, region, percent European ancestry (computed from genotype data on a set of validated Ancestry Informative Markers), family history of breast cancer, age at menarche, age at first birth, and body mass index. There was not a significant interaction of parity (0/1+) with the two TOX3/LOC643714 SNPs examined. Four SNPs in FGFR2, none of which had a significant overall association in the BWHS, were examined and an interaction with parity was observed for one, rs2981579 (p-interaction = 0.006). The per-allele odds ratio was 1.71 (1.17–2.49) among nulliparous women, whereas the comparable OR among parous women was 0.95 (0.81–1.13). Parity was associated with a reduced risk of breast cancer only among women who were homozygous for the risk allele A and this pattern appeared consistent for ER+/PR+ and ER-/PR-breast cancer. Three SNPs in chromosome 5p12 were examined and there was an overall interaction for one, rs4415084 (p-interaction = 0.03). The interaction was present only for ER+/PR+ tumors (p-interaction = 0.01). Parity was associated with a reduced risk of ER+ breast cancer among women homozygous for the C allele but not among women who carried one or more of the T risk alleles. Two large studies of European ancestry populations have found no significant interactions of reproductive factors with low-penetrance genetic polymorphisms. Smaller studies in Asian populations have found interactions of oral contraceptive use with FGFR2 variants and two independent U.S. studies showed an interaction of hormone replacement therapy with FGFR2 variants. The present results provide the first data on the interaction of parity with low-penetrance SNPs for breast cancer in AA women and, as such, need to be replicated in other data. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B92.