African American Breast Cancer Research Articles

Assessing the prevalence of compromised bone health among overweight and obese African-American breast cancer survivors: a case-control study.

Osteoporosis increases the risk of fracture and is often considered a late effect of breast cancer treatment. We examined the prevalence of compromised bone health in a sample of exclusively African-American (AA) breast cancer survivors since bone mineral density (BMD) varies by race/ethnicity in healthy populations. Using a case-control design, AA women in a weight loss intervention previously diagnosed and treated for stages I-IIIa breast cancer were matched 1:1 on age, race, sex, and BMI with non-cancer population controls (n = 101 pairs) from National Health and Nutrition Examination Survey (NHANES). Questionnaires and dual-energy x-ray absorptiometry (DXA) scanning were completed, and participants were categorized as having normal bone density, low bone mass, or osteoporosis using the World Health Organization (WHO) definition for femoral neck T-scores. The majority of these overweight/obese survivors were 6.6 (±4.7) years post-diagnosis, had stage II (n = 46) or stage III (n = 16) disease, and treated with chemotherapy (76 %), radiation (72 %), and/or adjuvant hormone therapies (45 %). Mean femoral neck BMD was significantly lower in cases vs. matched non-cancer population controls (0.85 ± 0.15 vs. 0.91 ± 0.14 g/cm(2), respectively; p = 0.007). However, the prevalence of low bone mass and osteoporosis was low and did not significantly differ between groups (n = 101 pairs; p = 0.26), even when restricted to those on adjuvant hormone therapies (n = 45 pairs; p = 0.75). Using conditional logistic regression, controlling for dietary factors and education, the odds of developing compromised bone health in AA breast cancer survivors was insignificant (OR 1.5, 95 % CI 0.52, 5.56). These null case-control findings challenge the clinical assumption that osteoporosis is highly prevalent among all breast cancer survivors, providing foundational evidence to support differences by race/ethnicity and body weight. Routine bone density testing and regular patient-provider dialogue is critical in overweight/obese AA breast cancer survivors to ensure that healthy lifestyle factors (e.g., ideal weight, regular weight-bearing exercises, dietary adequacy of calcium and vitamin D) support optimal skeletal health.

Measurement properties of the sedentary behavior strategy self-management instrument in African-American breast cancer survivors.

To examine the validity and reliability of a modified Sedentary Behavior Strategy Self-Management Scale (SBSMS) in a sample of breast cancer survivors. A total of 291 African-American (AA) breast cancer survivors completed the SBSMS, which was subjected to tests of reliability, structural validity, and tests of measurement equivalence/invariance (ME/I). A revised measurement model fit the data and demonstrated internal reliability and structural validity. Tests for ME/I revealed that the revised model had appropriate levels of invariance among weight status, educational, and years out from diagnosis groups, but not among age groups. The reliability and structural validity of the instrument was supported overall; however, revisions may be needed to support its validity in older AA breast cancer survivors.

Transition From Patient to Survivor in African American Breast Cancer Survivors

Breast cancer is the most common cancer among African American (AA) women, with a survival rate of 79%, lower than for other ethnic and racial groups in the United States. Minorities experience disparities in timeliness of care, delivery of culturally sensitive care, and outcomes. Transition from active treatment to survivorship presents an opportunity for exploration. This qualitative, grounded theory study examined the experiences and coping of AA women as they transition from being a breast cancer patient to being a breast cancer survivor. This study included 15 community-based AA women aged 35 to 75 years in Charleston, South Carolina, and Buffalo, New York, who had completed treatment for primary breast cancer between 6 and 18 months prior. A semistructured interview explored experiences as they finished treatment, support from family, role of spirituality, physical and emotional concerns, needs of the survivor, as well as suggestions for possible interventions for other survivors. Two investigators reviewed transcripts and coding to confirm and refine the findings. Four main themes were identified: perseverance through struggles supported by reliance on faith, persistent physical issues, anticipatory guidance needed after treatment, and emotional needs as important as physical. The transition from cancer patient to survivor is a pervasive time filled with stress, loss of safety net, and significant coping measures. Participants expressed the need to have support from another AA breast cancer survivor as they complete treatment. Nurses and providers can assess and address stressors in transition. Nurses should design patient-centered interventions using peers as direct support to promote effective coping strategies.

Abstract B35: Cumulative results from an investigation of transcriptome differences in breast cancer samples from African American and East African triple-negative breast cancer patients

Abstract We report our cumulative results of a multi-year study focusing on the genomic similarities and differences between Triple-negative breast cancer (TNBC) in native African and U.S. African patients. We used a cohort of African-American (AA) TNBC patients from South Florida and an indigenous cohort of Kenyan TNBC patients. Strong U.S. epidemiological data supports breast cancer (BC) as the second leading cause of cancer death among AA women, with a 20% greater mortality rate than that in Caucasian-American women (CA). AA women often present with tumors that are of higher grade and later stage and their relapse-free and overall survival period is significantly lower than CA. Additionally, TNBC has a higher prevalence in AA women. All of these observations lead to a much poorer prognosis for AA BC patients- thus defining the all-encompassing term “disparities in BC in women of African ancestry”. In our study, we used archived formalin fixed paraffin embedded (FFPE) blocks, collected across a stage-matched multi-ethnic U.S. cohort of node-negative TNBC from the University of Miami and similar TNBC samples from the Kijabe Hospital (Kenya). Using 10 μm scrolls from each block, total RNA was isolated, cDNA prepared, and hybridized to a breast cancer enriched gene expression array (Affymetrix Platform BC DSA Research Tool) in collaboration with Almac Diagnostics. Gene expression analysis was conducted using GeneSpring 12.1® analytical software. The raw data, a total of 60,856 gene/probes, was pre-processed using Robust MultiArray Average (RMA) algorithm; background corrected, log2 transformed to the baseline median of all samples and then quintile normalized. The samples that passed final QC were then filtered to remove low-intensity signals (< 20% signal). The final analysis cohort consisted of 10-AA, 13-CA and 21-Kenyan. PCA analysis revealed that the samples clustered well with respect to ethnicity. Unsupervised cluster analysis, based on ethnicity and genes (p value <.05, fold change >2.5), was performed. The resulting dendogram clearly segregated into distinct subgroups based on ethnicity, revealing a pattern of differential gene expression between the cohorts. A list of differentially expressed genes from each cohort (DEG) were selected using ANOVA analysis (fold change > 3.0, p value <.05) followed by the Benjamin and Hochberg method for multiple-testing correction. Finally, the lists of DEG were uploaded into GeneGo MetaCore to identify functionally enriched pathways. These analyses revealed significantly deregulated genes associated with the Wnt/β-catenin pathway in the AA cohort, as compared to the CA, suggesting that this pathway may contribute to the more aggressive phenotype in AA women diagnosed with TNBC. Additionally, significantly deregulated genes associated with the Oncostatin M pathway were discovered in the Kenyan cohort, as compared to the AA and CA tumors. In particular, STAT1 was significantly downregulated in the Kenyan cohort compared to the CA and AA. Thus, our results indicate gene expression differences within several key pathways across these ethnic groups. In summary, this study represents the first direct comparison of gene expression in TNBC specimens across U.S. CA and AA BC patients and Kenyan East Africans. These studies have important implications for further understanding BC ethnic disparities, as well as tailored approaches to prediction, prevention and therapeutic measures. Citation Format: Julie E. Getz, Mary E. Ahearn, Carmen Gomez, Biju Issac, Jennifer Clarke, Mark D. Pegram, Peter Bird, John D. Carpten, Lisa L. Baumbach. Cumulative results from an investigation of transcriptome differences in breast cancer samples from African American and East African triple-negative breast cancer patients. [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 B35. doi:10.1158/1538-7755.DISP13-B35

Abstract A86: Identifying system-level barriers to breast cancer treatment which lead to health disparities for vulnerable communities: A qualitative approach

Abstract Purpose of Study: This study is a part of a larger community-based participatory research (CBPR) project to decrease African-American and white breast cancer mortality disparities in Saint Louis, Missouri. Specifically, we explore the course of breast cancer treatment for a group of primarily low-income African American women living in North St. Louis at the time of diagnosis to identify factors that may contribute to discontinuation of breast cancer treatment. Methods: For this study, funded by Susan G Komen for the Cure, two sources of data (semi-structured interviews and medical record extraction) were explored to fully capture reasons for completion or discontinuation of prescribed treatment. We analyze data for 85 women for whom both sources of data were available and were treated at a large teaching hospital. Inclusionary criteria were at least 18 years of age and diagnosed with breast cancer while living in eight zip codes of North St. Louis, the latter chosen because they have been identified as part of a cluster of late stage diagnosis. Women were recruited via letters from the Missouri Cancer Registry and flyers prepared and distributed by community partner organizations. The approach had two components: (1) individual in-home interviews were conducted based on narrative theory to collect treatment history in the women's own voices; and (2) review of electronic medical records of the women to determine what supports were offered, and what treatment prescribed, to them. Patient narratives were coded using NVivo 10.0 and themes derived using grounded theory. Results: Two themes were most prevalent among the narratives from the women interviewed that suggest reasons why African-American women in the study may not have complete treatment prescribed. First, women did not connect radiation therapy with survival in the same way that they did surgery and chemotherapy. Rather, they described it in terms that made it seem optional, like breast reconstruction. Second, while women seemed to have been supported in terms of obstacles to treatment near the time of surgery, they reported no such services after receiving chemotherapy. Chart review revealed that patient navigation tapers off after surgery, with only one navigator employed by medical oncology and none in radiation oncology. Conclusions and Implications: Women describing radiation therapy as an optional treatment reflects a misunderstanding of the importance of radiation therapy in breast cancer survival. Relatedly, having navigators associated with each service (surgical, medical, and radiation oncology) who communicate regularly with one another may help to ensure that women complete prescribed treatment, thus decreasing the African American and white breast cancer mortality disparity in St. Louis. Further study is suggested to determine if these findings persist in other locations. Citation Format: Lailea Noel, Melody Goodman, Shahnjayla K. Connors, Dwayne Butler, Ron McMullen, Cheryl Oliver, Isaac McCullough, Sarah Gehlert. Identifying system-level barriers to breast cancer treatment which lead to health disparities for vulnerable communities: A qualitative approach. [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 A86. doi:10.1158/1538-7755.DISP13-A86

Abstract C32: Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings

Abstract Introduction/Objectives: Research demonstrates that after a breast cancer diagnosis, young women, especially those of racial and ethnic groups, may experience a more negative impact on their quality of life, emotional functioning, and reproductive health than older women. For women under the age of 45, African American women have the highest breast cancer incidence of any racial/ethnic group, and there is an increased risk of hereditary breast cancer among Jews who carry BRCA mutations. In conjunction with Sisters Network Inc. and Sharsheret, The Centers for Disease Control and Prevention launched a formative evaluation to understand African American and Jewish young breast cancer survivors' (YBCS) psychosocial and reproductive health needs and preferred communication channels to obtain needed health information. Methods: Sisters Network Inc. conducted four focus groups with African American YBCS. Sharsheret conducted four groups with Jewish YBCS. Thematic analysis identified major themes/patterns within and across the focus groups. Results: Fertility and sexual health were major YBCS concerns. Participants reported barriers to obtaining psychosocial and reproductive health information, including sexual taboos and lack of provider sensitivity to address these needs. Participants said that breast cancer resources are not tailored to YBCS. Participants preferred to receive breast cancer information via multiple channels, including written materials, the Internet, telephone and smartphone applications. Discussion/Implications: African American and Jewish women encounter similar barriers to obtaining psychosocial and reproductive health information. Both groups report difficulty in obtaining relevant health information and advice from their medical providers. Study findings may be used for developing of culturally-appropriate communication and interventions for YBCS that would help eliminate breast cancer health disparities in YBCS. Citation Format: Temeika L. Fairley, Natasha Buchanan, Ashani Johnson-Turbes, Leslie R. Schover, Angela R. Moore, Brandie Yancy, Dara Schleuter, Mary-Ann K. Hall, Kelly P. Hodges, Rochelle Shoretz. Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings. [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 C32. doi:10.1158/1538-7755.DISP13-C32

Abstract C56: The role of BetaB2-crystallin in progression of colorectal and breast cancers in African Americans

Abstract Purpose: African-American (AA) breast cancer (BC) and colorectal cancer (CRC) patients experience higher mortality rates than Non-Hispanic Caucasian (CA) patients. These disparities are thought to be due to race/ethnicity-specific tumor molecular biology. Our initial gene expression investigations have identified a Beta B2-Crystallin (CRYBB2) gene that is preferentially over-expressed in CRC of AA patients. However, the precise role of CRYBB2 in aggressiveness of CRC and BC has not been examined. Therefore, we hypothesize that biological mechanism linked to CRYBB2 could contribute to the disparate progression of CRC and BC in AA patients. Experimental Design: Gene expression studies were performed using Affymetrix Human Genome U133 Plus 2.0 arrays and mRNA samples extracted from 10 fresh frozen Stage III CRCs (5 from AA and 5 from CA) that were previously analyzed for the microsatellite instability (MS) status. Established CRC (HT29 and SW480) and BC (MBA-MD 231) cell lines were used to examine the phenotypic expression of CRYBB2. Also, paired lesions of human CRC (hCRC) and human mice CRC (hmCRC) xenograft were assessed for CRYBB2 by western blot and immunofluorescence (IF). To study the involvement of CRYBB2 in CRC and BC biology, siRNA mediated gene silencing was used to inhibit CRYBB2 expression. The apoptosis of CRC and BC cells after knockdown of CRYBB2 was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The epithelial-mesenchymal transition (EMT) of CRC and BC cells was analyzed by western blot for E-cadherin, MM9 and vimentin expression. Western blot analysis was performed on lysates of CRC and BC cells to assess the effect of CRYBB2 knockdown for expression/ activation of the AKT, and mitogen-activated protein kinase pathway proteins. Results: Our microarray analyses have suggested that several key genes involved in tumor metastasis (CRYBB2, VSNL-1and PFN2) are up-regulated in MS-CRCs of AA but down regulated in MS-CRCs of CA patients. The phenotypic expression of CRYBB2 was found to be higher in CRC tissues as compared to matching normal tissues. Over-expression of CRYBB2 correlated with metastatic CRC and N-cadherin expression and the expression of CRYBB2 was substantially increased in metastatic lesion of CRC and BC xenografts as compared to the primary tumors. Knockdown of CRYBB2 induced apoptosis in CRC and BC cells. In addition, Knockdown of CRYBB2 suppressed EMT signatures, such as decreasing the expression of MMP9, vimentin (mesenchymal markers) and increasing the expression of E-cadherin (epithelial marker). Furthermore, depletion of CRYBB2 decreased the phosphorylation of AKT (p-AKT) in CRC and BC cells. CRYBB2 was mainly localized in cytoplasm of BC and CRC cells. Conclusions: Our data suggest that CRYBB2 inhibits apoptosis, activates EMT process and AKT phosphorylation by which it contributes the aggressiveness of CRC and BC. It may serve as a promising biomarker for identifying CRC and BC patients at high risk for metastases. It may also be useful as a therapeutic target to inhibit the growth and metastasis of CRC and BC. These studies are supported by NIH/NCI funds (R21-CA171251 and U54- CA 118948). Citation Format: Harvey L. Bumpers, Venkat Katkoori, Dongquan Chen, Upender Manne. The role of BetaB2-crystallin in progression of colorectal and breast cancers in African Americans. [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 C56. doi:10.1158/1538-7755.DISP13-C56

Abstract C31: Racial/ethnic differences in cancer survivorship: The example of breast cancer-related lymphedema severity

Abstract Introduction: Breast-cancer related lymphedema (BCRL) is a persistent adverse outcome of cancer treatment that affects the physical health and quality of life of up to 1 in 3 of the 2.9 million breast cancer survivors in the US. For those with BCRL, known predictors of progression include BMI, type of surgery and radiation treatment, each of which is independently associated with race/ethnicity. Observational studies have found that Black/African-American women are more likely than Whites to develop BCRL, but no studies have explored the association of race/ethnicity with BCRL severity. Method: The WISER Survivor Trial has collected baseline data from 149 overweight (BMI≥25) women with upper body BCRL (61% White; 39% African-American). Ordinal logistic regression modeling was used to explore the associations of known predictors of lymphedema progression and race/ethnicity with lymphedema grade (0-3). Results: In univariate analysis, higher age at breast cancer surgery, being African-American, and having had chemotherapy or radiation therapy were significantly associated with higher lymphedema grade. Multivariate analysis revealed that race mediates the relationship between BMI and lymphedema grade such that being African-American AND having an elevated BMI is associated with higher lymphedema grade while elevated BMI is not associated with higher lymphedema grade among White women, such that at equivalent BMI, African-American women were 20% more likely to have a higher lymphedema severity (OR=1.20 [1.00, 1.44]; p=0.043). Discussion: These findings point to a need for clinicians to be aware of increased risk of lymphedema for overweight African-American female breast cancer survivors. The cause of the observed interaction of African-American race/ethnicity and BMI on lymphedema severity remains to be elucidated. Previous studies have observed a relationship of higher lymphedema grade with higher costs to care for the condition, as well as worse functional ability of the upper body. Therefore, increased odds of higher lymphedema grade among African-American women with elevated BMI could contribute to a meaningful difference in the burden of breast cancer survivorship for this underserved minority population. To further elucidate this relationship, prospective collection on health-care costs for breast cancer survivors with lymphedema is warranted. This work has implications to affect care for and quality of life of up to 1 in 3 of the 2.9 million breast cancer survivors in the US who have BCRL. Citation Format: Lorraine T. Dean, Taehoon Kim, Matthew Herling, Justin Brown, J Sanford Schwartz, Kathryn Schmitz. Racial/ethnic differences in cancer survivorship: The example of breast cancer-related lymphedema severity. [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 C31. doi:10.1158/1538-7755.DISP13-C31

Abstract PR12: Nuclear HSET, a predictor for metastasis, disease relapse, and poor survival, is a racial disparity biomarker in triple-negative breast cancer patients

Abstract Introduction: Human spleen, embryo, and testes protein (HSET, also known as KifC1) is a minus end-directed kinesin that has recently been implicated in carcinogenesis. HSET overexpression predicts lung cancer metastasis to the brain, and HSET is upregulated in triple-negative (TN) breast cancer that most commonly occurs in African American (AA) patients. While mounting evidence links HSET to tumorigenesis, especially in the breast, HSET is yet to be evaluated as a clinical biomarker in breast cancer. Here, we investigated the association of HSET with demographic and clinicopathological factors and disease progression in breast tumors among ethnically-distinct populations. Methods: HSET expression was analyzed by immunohistochemistry of formalin-fixed, paraffin-embedded breast carcinoma core biopsies from 149 African American (AA) and 44 Caucasian (CA) totaling 193 patients. Immunostaining was assessed semi-quantitatively for the nucleus and cytoplasm separately. Weighted indices were correlated with tumor and patient characteristics (including ethnicity) along with clinical outcomes. Results: We found that nuclear HSET expression was highly associated with race, with AA women being thrice as likely to present with nuclear localization compared to CA regardless of TN status. Nuclear HSET expression was also significantly associated with the proliferation marker Ki67 and clinicopathological factors like tumor grade, stage, and size; Nottingham prognostic index (NPI); and TN status. High HSET expression was exclusively associated with poorer outcomes in AA patients and not in CA patients. Within the AA population subset, patients with the highest tertile of HSET expression demonstrated the poorest overall survival (HR = 4.1, p = 0.007), progression-free survival (HR = 3.0, p = 0.014), and metastasis-free survival (HR = 3.5, p = 0.01). These associations were also significant using HSET as a continuous variable in multivariate analysis when potentially confounding factors like age, TN status, and tumor stage were matched. Interestingly, overall, progression-free, and metastasis-free survival were significantly associated with nuclear but not cytoplasmic HSET. Conclusions: Expression of nuclear HSET is a valuable prognostic biomarker in AA but not in CA breast cancer patients, underscoring its role in the aggressiveness of this disease in the AA population. HSET overexpression appears to be correlated with poorer prognosis in AA breast cancer patients even after adjusting for age, TN status and other tumor characteristics. In summary, our study is the first to identify and report HSET as a novel clinical biomarker of worse prognosis in AA women with breast cancer. This abstract is also presented as Poster C17. Citation Format: Angela Ogden, Gabriela Oprea-Ilies, Padmashree CG Rida, Dana Nickleach, Yuan Liu, Guilherme Cantuaria, Ritu Aneja. Nuclear HSET, a predictor for metastasis, disease relapse, and poor survival, is a racial disparity biomarker in triple-negative breast cancer patients. [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 PR12. doi:10.1158/1538-7755.DISP13-PR12

Genetic variation in cell cycle regulatory gene AURKA and association with intrinsic breast cancer subtype.

AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. In race-stratified analyses adjusted for age and African ancestry, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate SNP associations with breast cancer. In a race-combined analysis with similar adjustment, these associations were also examined by intrinsic breast cancer subtype. Using dominant models, most AURKA SNPs demonstrated no association with breast cancer in the race-stratified analyses. Among AA, rs6092309 showed an inverse association with breast cancer (OR = 0.69, 95% CI = 0.53-0.90). In the race-combined analyses, rs6099128 had reduced ORs for luminal A (OR = 0.76, 95% CI = 0.60-0.95) and basal-like breast cancer (OR = 0.54, 95% CI = 0.37-0.80). Rs6092309 showed a similar pattern of association with each subtype. Three SNPs (rs6014711, rs911162, rs1047972) had positive associations with basal-like breast cancer, and ORs reduced or close to 1.00 for other subtypes. Our results suggest inverse associations between some AURKA SNPs and overall breast cancer in AA. We found differential associations by specific subtypes and by race. Replication of these findings in larger AA populations would allow more powerful race-stratified subtype analyses.

PO3-17: Hypermethylation and hypomethylation of IGF-II DMRO (Insulin like growth factors-II Differentially Methylated Region) correlated to increased or decreased expression of IGF-II in breast cancer cells and paired breast tissues of African American and Caucasian breast cancer patients

PO3-17: Hypermethylation and hypomethylation of IGF-II DMRO (Insulin like growth factors-II Differentially Methylated Region) correlated to increased or decreased expression of IGF-II in breast cancer cells and paired breast tissues of African American and Caucasian breast cancer patients

Abstract 3213: Rosehip (Rosa canina) extracts prevent MAPK and AKT-mediated cell proliferation in African American triple-negative breast cancer cells

Abstract Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor-2 (HER-2), the estrogen receptor (ER), and the progesterone receptor (PR). The high prevalence of triple negative tumors in young women is more commonly observed in young African American (AA) women. Currently, the existing targeted therapy is of minimal benefit in TNBCs. Akt and MAPK have been shown to promote cell proliferation in triple negative breast cancer and MAPK expression may be an underlying mechanism contributing to the generation of chemo-resistance in triple-negative breast cancer. Due to major concerns involving the occurrence of side effects and the emergence of drug-resistant cancer cells, there has been growing interest in the use of naturally occurring molecules with chemo-preventive and chemo- therapeutic properties in cancer treatment. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with diarrhea, gastritis, and rheumatoid arthritis and have been shown to prevent cell proliferation in glioblastomas. This study investigated the efficacy of rosehip extracts in preventing cell proliferation in African American triple negative (HCC70, HCC1806) and luminal (HCC1500) breast cancer cell lines. Each of the breast cancer cell lines were treated with rosehip extracts (1mg/mL -25ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when known inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of these cell lines with these Rosehip extracts (1mg/mL -25ng/mL) selectively decreased AKT, MAPK, p70S6K, and S6 phosphorylation suggesting these extracts prevent AA TNBC cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from cell cycle analysis by flow cytometry, western blot analysis, as well as apoptosis studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Rosehip extracts also have a synergistic effect with Doxorubicin (20µM), a chemotherapeutic agent used to treat patients with breast cancer, in preventing triple negative breast cancer cell proliferation. Taken together these data suggest that rosehip extracts are capable of decreasing cell proliferation in African American triple negative breast cancer cells without promoting apoptosis and demonstrate a synergistic inhibition of cell proliferation with Doxorubicin, and rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for triple negative breast cancer. Citation Format: Patrice Cagle, Tonisha Coburn, Patrick M. Martin. Rosehip (Rosa canina) extracts prevent MAPK and AKT-mediated cell proliferation in African American triple-negative breast cancer cells. [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 3213. doi:10.1158/1538-7445.AM2014-3213

Abstract 2368: Differential gene expression in key oncolytic pathways between node-matched Caucasian-American, African-American and East African triple-negative breast cancer patients

Abstract African-American (AA) women have a 20% greater mortality rate from breast cancer (BC) than that observed in Caucasian-American women (CA). Additional BC disparities in AA women include later stage presentation with higher tumor grade, and increased occurrence of Triple-negative breast cancer (TNBC). In this study, we performed a series of gene expression array analyses on archived formalin fixed paraffin embedded (FFPE) blocks from a multi-ethnic U.S. cohort of node-negative (N0) TNBC samples, in addition to a cohort of (N0) TNBC samples from East African patients (Kijabe,Kenya). Using 10 μm scrolls from each FFPE block, total RNA was isolated, cDNA prepared, and hybridized to a breast-enriched gene expression array (Affymetrix, BC DSA Research Tool®). Expression analysis was conducted using GeneSpring 12.1® analytical software. After QC analyses, the final study cohort consisted of 10-AA, 13-CA and 21-Kenyan samples. PCA analysis revealed that the samples clustered well with respect to ethnicity. Unsupervised cluster analysis, based on ethnicity and genes (p value 2.5), was performed. The resulting dendogram clearly segregated into distinct subgroups based on ethnicity, revealing a pattern of differential gene expression between the cohorts. A list of differentially expressed genes from each cohort (DEG) were selected using ANOVA analysis (fold change > 3.0, p value <.05) followed by the Benjamin/Hochberg method for multiple-testing correction. Finally, the lists of DEG were uploaded into GeneGo MetaCore to identify functionally enriched pathways. These analyses revealed differentially expressed genes pathways enriched for cytoskeletal remodeling, cell adhesion and EMT pathways. In particular, significantly deregulated genes associated with the Wnt/β-catenin pathway were observed in the AA cohort as compared to the CA, suggesting that this pathway may contribute to the more aggressive phenotype in AA women diagnosed with TNBC. Additionally, significantly deregulated genes associated with the Oncostatin M pathway were discovered in the Kenyan cohort, as compared to the AA and CA tumors. In particular, STAT1 was significantly downregulated in the Kenyan cohort compared to the CA and AA. Thus, our results indicate gene expression differences within several key oncolytic pathways across these ethnic groups. These results are being technically and biologically validated through several parallel approaches. Validation study results will be presented. In summary, this study represents the first direct comparison of gene expression in TNBC specimens across U.S. CA and AA BC patients and Kenyan East Africans. These studies have important implications for further understanding BC ethnic disparities, as well as future tailored approaches to prediction, prevention and therapeutic advances. Citation Format: Julie Getz, Mary E. Ahearn, Carmen Gomez, Mark Pegram, Peter Bird, John Carpten, Lisa L. Baumbach-Reardon. Differential gene expression in key oncolytic pathways between node-matched Caucasian-American, African-American and East African triple-negative breast cancer patients. [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 2368. doi:10.1158/1538-7445.AM2014-2368

Enhanced down-regulation of ALCAM/CD166 in African-American Breast Cancer.

BackgroundVariation in tumor biology in African-American (AA) and Caucasian (CAU) women with breast cancer is poorly defined. Activated leukocyte cell adhesion molecule (ALCAM) is a bad prognostic factor of breast cancer yet it has never being studied in the AA population. We tested the hypothesis that ALCAM expression would be markedly lower in cases of AA breast cancer when compared to CAU.MethodsCases of breast cancer among AA (n = 78) and CAU (n = 95) women were studied. Immunohistochemical staining was used to semi-quantitatively score ALCAM expression in tumor and adjacent non-tumor breast tissues. Clinico-pathological characteristics including histological type, histological grade, tumor size, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status were abstracted, and their association with ALCAM expression tested.ResultsUnivariate analysis revealed that the level of ALCAM expression at intercellular junctions of primary tumors correlates with histological grade (AA; p = 0.04, CUA; p = 0.02), ER status (AA; p = 0.0004, CAU; p = 0.0015), PR status (AA; p = 0.002, CUA p = 0.034) and triple-negative tumor status (AA; p = 0.0002, CAU; p = 0.0006,) in both ethnic groups. Multivariate analysis demonstrated that ethnicity contribute significantly to ALCAM expression after accounting for basal-like subtype, age, histological grade, tumor size, and lymph node status. Compared to CAU tumors, the AA are 4 times more likely to have low ALCAM expression (p = 0.003).ConclusionsMarkedly low expression of ALCAM at sites of cell-cell contact in primary breast cancer tumors regardless of differentiation, size and lymph node involvement may contribute to the more aggressive phenotype of breast cancer among AA women.

Racial differences in radiation-induced toxicity and cytokine expression levels.

e17570 Background: African American (AA) breast cancer patients treated with breast conserving therapy reportedly have more treatment related toxicity and worse clinical outcomes than their Caucasi...

Breast Cancer in African Americans

The purpose of this synthesis is to explore the experience of the transition from cancer patient to survivor in African Americans with breast cancer, addressing the risk/ protective factors that have an influence on successful transition using the social ecological model. The investigator searched CINAHL, PubMed, and PsycInfo databases. Articles were assessed for content addressing risk and protective factors of transition in African American breast cancer survivorship. Eleven research articles were obtained and synthesized. Risk and protective factors exist at all levels of the social ecological model. Emotional issues are prevalent after the cessation of cancer treatment, enhanced by the lack of social support in this population. Spirituality was shown to be present in many levels as a protective factor during this period. The entrance to survivorship represents a time of increased stressors and subsequent coping. Through careful identification of influencing factors, health care providers can develop strategies to attenuate the emotional distress and negative complications of the transition specific to this vulnerable population. Illuminating the experiences of African American women during this transition period provides insight into the interventional needs during and after the cessation of breast cancer treatment.

A Community-Based Exercise and Support Group Program in African-American Breast Cancer Survivors (ABCs)

African-American (AA) women have higher rates of breast cancer (BCa) mortality than Caucasian women, and a recent study using data from the Surveillance, Epidemiology and End Results (SEER) registry suggests that this disparity may be due, in part, to the poorer health status of AAs at diagnosis and not treatment related issues. Randomized controlled trials involving supervised aerobic and resistance exercise have shown improved body composition and improvement in cancer-related biomarkers in BCa patients and may lead to improved recurrence and survival rates; however, most trials have focused on Caucasians and many have been conducted in academic- and clinic-based settings. We evaluated the feasibility of conducting a 20-week, supervised, resistance training, group exercise intervention coupled with a support group and home walking program utilizing facilities and personnel at a community cancer support center (The Gathering Place, Beachwood, Ohio) in AA Stage I-III BCa survivors who were within 12 months of completing treatment (surgery, chemotherapy, and/or breast irradiation); and, evaluated the potential effects of this intervention on physical measures and cancer-related biomarkers. 27 patients provided informed consent and 19 participated in the program. On average, attendance rates were 70.0% ± 19.1% for the exercise sessions and 63.1% ± 13.8% for the support group. We observed a significant decrease in circulating C-peptide levels (B: 893.9 ± 399.1 pg/mL; EOI: 723.9 ± 319.0 pg/mL; p=0.01). Although we did not observe a significant decrease in weight in the entire sample, there was a significant decrease in waist circumference and percent total body fat among those who attended 70% or more of the exercise sessions. In summary, we demonstrated that conducting lifestyle interventions in AA BCa survivors in a community setting is feasible. Future interventions should invoke strategies to enhance adherence and include a structured dietary intervention to enable greater weight loss.

Abstract P3-01-03: Vitamin D levels at breast cancer diagnosis: Association with patient and tumor characteristics

Abstract Background: Despite many preclinical studies showing the anti-neoplastic effects of vitamin D on breast cancer, findings from epidemiologic studies and randomized trials remain inconclusive. It is possible that tumor heterogeneity in breast cancer may mask these associations. Variations in vitamin D metabolism may explain some racial disparities in breast cancer. We aimed to examine the association of serum vitamin D levels with individual patient and tumor characteristics. Methods: We conducted an IRB approved retrospective chart review, identifying all breast cancer patients with documented pretreatment serum levels of 25-hydroxyvitamin D (25(OH)D) between February 2011-May 2013. The following clinical data were collected for each patient: age at diagnosis, ethnicity, menopausal status, tumor size (mm), lymph node status, estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Based on ER, PR, and HER2, patients were categorized into three molecular subtypes: 1) Hormone receptor (HR)+ (ER or PR positive, HER2 negative), 2) HER2+, and 3) triple negative (TN; ER, PR, and HER2 negative). Descriptive variables were analyzed using a one-way Anova test. Results: Among the 200 breast cancer patients identified, the mean age was 55.9 years (range 29-90). Ethnicities of the patients were as follows: 104 (52%) Caucasian, 43 (22%) African American, 29 (15%) Hispanic, and 16 (8%) Asian. Seventy six patients (38%) were premenopausal, and 124 (62%) were postmenopausal. African Americans were found to have higher rates of triple negative tumors compared to all other ethnicities (24.4% vs. 11.6%, p = 0.029). Younger women had lower mean serum 25(OH)D levels compared to older women (p = 0.033). Lower mean 25(OH)D levels were seen in ER negative tumors compared to ER positive tumors (p = 0.0102). Mean 25(OH)D levels were lower in African American, Hispanic, and Asian breast cancer patients when compared to Caucasians (p = 0.0004). When stratifying by menopausal status, serum 25(OH)D levels differed more by tumor characteristics among premenopausal women than postmenopausal women. In premenopausal women, lower vitamin D levels were seen in patients who were African Americans (p = 0.0185), and with tumors that were ER negative (p = 0.0083). There was also a trend toward lower mean vitamin D levels in those with TN breast cancer compared to other molecular subtypes. Conclusion: In premenopausal women, lower vitamin D levels were associated with African American race, younger age, and ER negative tumors. This may suggest that African Americans have defective vitamin D metabolism that may contribute to a more aggressive breast cancer phenotype. Further studies are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-01-03.

Differentially Expressed Transcripts and Dysregulated Signaling Pathways and Networks in African American Breast Cancer

African Americans (AAs) have higher mortality rate from breast cancer than that of Caucasian Americans (CAs) even when socioeconomic factors are accounted for. To better understand the driving biological factors of this health disparity, we performed a comprehensive differential gene expression analysis, including subtype- and stage-specific analysis, using the breast cancer data in the Cancer Genome Atlas (TCGA). In total, 674 unique genes and other transcripts were found differentially expressed between these two populations. The numbers of differentially expressed genes between AA and CA patients increased in each stage of tumor progression: there were 26 in stage I, 161 in stage II, and 223 in stage III. Resistin, a gene that is linked to obesity, insulin resistance, and breast cancer, was expressed more than four times higher in AA tumors. An uncharacterized, long, non-coding RNA, LOC90784, was down-regulated in AA tumors, and its expression was inversely related to cancer stage and was the lowest in triple negative AA breast tumors. Network analysis showed increased expression of a majority of components in p53 and BRCA1 subnetworks in AA breast tumor samples, and members of the aurora B and polo-like kinase signaling pathways were also highly expressed. Higher gene expression diversity was observed in more advanced stage breast tumors suggesting increased genomic instability during tumor progression. Amplified resistin expression may indicate insulin-resistant type II diabetes and obesity are associated with AA breast cancer. Expression of LOC90784 may have a protective effect on breast cancer patients, and its loss, particularly in triple negative breast cancer, could be having detrimental effects. This work helps elucidate molecular mechanisms of breast cancer health disparity and identifies putative biomarkers and therapeutic targets such as resistin, and the aurora B and polo-like kinase signaling pathways for treating AA breast cancer patients.

Replication of Breast Cancer Susceptibility Loci in Whites and African Americans Using a Bayesian Approach

Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993-2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer-related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.