African American Breast Cancer Research Articles

Abstract IA29: Race, ethnicity, and outcomes in breast cancer

Abstract The racial divide in breast cancer outcomes is well known. Breast cancer is the most common cause of cancer in women in the United States, and the second leading cause of cancer death.1 Black race is associated with a worse prognosis in operable breast cancer2 and in other hormone dependent cancers such as uterine and prostate cancer, but generally not other cancer types.3,4 Black women are more likely to present with advanced stage disease5, have triple negative breast cancer (TNBC), exhibit greater non-adherence and poorer tolerance to chemotherapy6 and endocrine therapy7, and have more comorbidities8 and experience more disparities in care.9-11 Black race has also been associated with worse outcome in male breast cancer.12 Although breast cancer incidence and mortality have declined by about 35% in the United States since 1990, mortality rates have declined less in black women, contributing to a widening of the racial gap which has contributed to about a 35% higher mortality rate for black women compared with others.13 However, a widening racial gap has also been observed for women in the U.S. Department of Defense healthcare system, suggesting that factors other than disparities in care may be playing a role. 14 With regard to ethnicity, Hispanic women also exhibit higher rates of TNBC, but otherwise experience similar outcomes as non-Hispanic women. There is emerging evidence that differences in outcomes may be due in part due to factors other than disparities in care. In this review, we explore some of the biological factors that may be contributing to the racial divide in breast cancer.

Abstract PR04: The molecular biology of nuclear and mitochondrial regulatory noncoding RNAs differs between white and African American patients with triple-negative breast cancer

Abstract Noncoding RNAs (ncRNAs) are molecules that do not code for proteins but regulate cell physiology via multiple mechanisms. Through studies of hundreds of human datasets from healthy individuals and patients we found for two categories of ncRNAs that their composition and abundances depend on a person's gender, population, race, and several other variables. These two categories are: a) isoforms of microRNAs (miRNAs), also known as isomiRs; and, b) fragments derived from transfer RNAs (tRNAs), also known as tRNA fragments or tRFs. Traditionally, a miRNA genomic locus was thought to give rise to a single mature miRNA (archetype). The archetype's sequence was recorded in public databases and used to design reagents and experiments. Advances in sequencing technology have revealed that miRNA loci simultaneously give rise to multiple isomiRs, i.e. isoforms of the archetype miRNAs, with distinct endpoints and abundances. Importantly, isoforms are loaded on the RNA-induced silencing complex (RISC) thereby entering the RNA interference (RNAi) pathway where they guide sequence-based RISC interactions with specifically targeted messenger RNAs (mRNAs) and ncRNAs, thusly controlling the abundance of those transcripts. Moreover, miRNAs have been linked to a multitude of cellular processes in health and disease. Analogously, the genomic loci harboring tRNAs were thought to give rise to only the mature tRNA sequence, the latter being an integral part of the translation of mRNAs into amino acid sequences. As with isomiRs, modern sequencing technology revealed the existence of tRNA fragments that co-exist with the corresponding full-length mature tRNAs. Fast accumulating evidence has already linked tRFs to cell growth, cell proliferation, response to DNA damage, translation initiation, response to stress, etc. Some tRFs have also been found on RISC and to participate in RNAi, similarly to isomiRs. We investigated isomiRs and tRFs in human samples, in health and disease. Specifically, we used public transcriptomic datasets from the 1,000 Genomes Project and from The Cancer Genome Atlas (TCGA) repository at the National Institutes of Health. By analyzing samples from nearly five hundred healthy individuals we found that both the isomiR profiles and the tRF profiles depend on a person's gender, population, race, tissue and tissue state. In the case of tRNA fragments, we found that they derive from nuclear and from mitochondrial tRNAs. By focusing on data from cancer patients we found that the dependencies we uncovered extend to the disease context as well. In particular, our analysis of samples from White and African-American triple negative breast cancer (TNBC) patients showed that there exist extensive and significant differences in the isomiR and tRF profiles between the two races. More specifically, we identified many isomiRs and tRFs that are differentially abundant in TNBC samples from White patients vs. TNBC samples from African-American patients. We also found that analogous isomiR and tRF differences distinguish the normal breast samples of White and African American subjects. When we integrated the isomiR information with mRNA expression values from the corresponding TCGA TNBC samples we found that the molecular biology differences in the isomiR and tRF profiles were indeed reflected in the abundance of protein coding genes, a result that could serve as a starting point for deeper research activities towards explaining health disparities in this breast cancer subtype. Our studies suggest that miRNA isoforms and tRNA fragments are active novel members of the molecular biology of TNBC. Future studies of this disease will need to also consider these molecules given that they represent a component of the cell's regulatory layer that depends on the patient's race. This abstract is also presented as Poster C62. Citation Format: Aristeidis G. Telonis, Phillipe Loher, Yi Jing, Eric Londin, Isidore Rigoutsos. The molecular biology of nuclear and mitochondrial regulatory noncoding RNAs differs between white and African American patients with triple-negative breast cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr PR04.

Abstract IA02: Genetic, environmental, and biological contributions to racial disparities in lung cancer incidence

Abstract Lung cancer is the leading cause of cancer-related deaths in the United States (1). In addition, there are significant disparities in lung cancer across populations. Compared with European Americans, African Americans are disproportionally affected by lung cancer, both in terms of incidence and survival (2,3). Lung adenocarcinoma among African Americans is 1.30 (1.10 - 1.90) times higher compared with European Americans; squamous cell carcinoma 1.80 (95% C.I. 1.1 - 2.3) times higher (4). There are also differences in lung cancer outcomes between European Americans and African Americans (2,5), some of which may be due to differences in cell biology between these two populations. However, studies have generally shown that differences in access to care may explain most of the variance in survival times (5-7). In addition, the gains in survival over the past 20 years among lung cancer patients have been similar in both European Americans and African Americans. Thus, the causal factors – genetic, environmental or otherwise – that lead to a greater incidence of lung cancer in African Americans are largely unknown. Smoking is the strongest risk factor for lung cancer development. However, several studies suggest that smoking prevalence and behaviors do not fully explain the disparity in lung cancer incidence. For example, African Americans have a lower smoking prevalence than European Americans and only 5.8% of African Americans are heavy smokers, compared with 19.2% of European Americans (8). In fact, when one compares smoking rates across ethnic groups matched for equal levels of smoking, African Americans still experience a higher burden of lung cancer incidence (8) - although this is attenuated with higher numbers of cigarettes smoked per day. This has led some to suggest that African Americans are more susceptible to the carcinogenic effects of tobacco at lower doses. However, this has not been empirically tested. It is possible that there are differences in nicotine and tobacco carcinogen metabolism between European Americans and European Americans that could account for the differences in cancer incidence between. On average, 72% of nicotine is converted to cotinine, the primary proximate metabolite of nicotine (9). Racial and ethnic differences in urinary (10,11) and blood cotinine (11-13) concentration per cigarette smoked have been well established. In addition, studies have found that levels of NNK metabolites (11,14) and thiocyanate (11) are higher in African Americans compared with European Americans. However, no clear genes or pathways have yet been identified that explain the disparity. And, given the strong relationship between smoking and lung cancer, it is hard to completely discount smoking as a cause of incidence disparities (8). Other risk factors to explain higher lung cancer incidence among African Americans include genetics, SES, smoking, BMI, and/or alcohol consumption. Recent studies show that the same loci associated with risk of lung cancer in European American smokers, i.e., chr15q25, are also associated with lung cancer in African Americans (15-18). Disparities in lung cancer incidence could be driven by the environment. For example, a recent study found that African Americans were more likely to reside in areas with the highest levels of air toxin exposure (19). Studies of breast and prostate cancer (20,21) have shown that whatever the cause of cancer health disparities, the consequences of these disparities manifest themselves as differences in the molecular and cell biology of the cancer. In lung cancer, we have explored the biological differences between lung cancer in European Americans and African Americans. These studies show that while some of the perturbed pathways in lung cancer remain the same for European Americans and African Americans, there are specific differences distinct to African Americans. Continued research efforts in the field are needed to determine the contribution of smoking, and indeed other factors, to lung cancer disparities. This work needs to be complemented with research that dissects the consequences of these disparities and the translation of these discoveries into improved patient care.

Abstract C06: Examining reasons for breast cancer disparities in African American women in Duval County, FL

Abstract Background/Purpose: Cancer registry data suggests that Duval County (greater Jacksonville, FL) has the highest breast cancer mortality rate for African American (AA) women in the southeastern US. Recent research revealed that race, residence, and insurance were associated with significantly poorer breast cancer outcomes in this area. Therefore we conducted a series of focus groups with AA breast cancer survivors from the urban core of Jacksonville, FL to directly address the disparities observed in our quantitative data. Methods: A series of focus groups were conducted to obtain qualitative data topics that included: breast cancer beliefs; delays to diagnosis and treatment; disparities; and health behaviors. Results: A total of 56 AA breast cancer survivors living in the urban core, with either Medicaid or who were uninsured, participated in the focus groups. Mean age was 62 years, with an average of 3.4 years since diagnosis. Only 21% of women were employed. Participants reported their mean time to see a doctor initially for their breast cancer was 39 days, and mean time to first treatment was 178 days. Participants responded that fear, financial limitations, and personal beliefs played the biggest roles in delays to diagnosis and treatment. Participants responded that poor health behaviors, genetics, lack of education, and personal beliefs accounted for both causing breast cancer, and the disparities observed in breast cancer mortality, and felt that environmental factors from living in the urban core also contribute. Conclusions: Our findings highlight several areas for potential intervention to reduce disparities in breast cancer. Citation Format: Sarah Osian, Monica Albertie, David Monticalvo, Steven Ames, Laila Samiian, Gerardo Colon-Otero. Examining reasons for breast cancer disparities in African American women in Duval County, FL. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C06.

Engaging African Americans in developing an intervention to reduce breast cancer recurrence: A brief report.

BackgroundTo develop a culturally appropriate lifestyle intervention, involvement of its intended users is needed.MethodsMembers of an African American (AA) breast cancer support group participated in two 4-hour guided discussions, which were audiotaped, transcribed, and analyzed to guide the content.ResultsThe support group collaborated with researchers to develop 24 experiential nutrition education sessions using a social cognitive framework and incorporating self-regulation skills (goal-setting, self-monitoring, problem-solving, stimulus control) and social support to enhance self-efficacy for changes in dietary intake.ConclusionsCommunity engagement fostered autonomy, built collaboration, and enhanced the capacity of AA breast cancer survivors to participate in developing a lifestyle intervention.

Determinants of adherence to nutrition-related cancer prevention guidelines among African American breast cancer survivors.

BackgroundMortality rate for breast cancer is higher among African American (AA) women than for women of other racial/ethnic groups. Obesity, also higher among AA women, may increase the risk of breast cancer development and recurrence. Lifestyle factors such as healthy nutrition can reduce the rate of obesity and breast cancer. This study examined the determinants of adherence to nutrition-related cancer prevention guidelines among AA breast cancer survivors.MethodsAA breast cancer survivors (n=240) were recruited from a breast cancer support group to complete a lifestyle assessment tool for this cross-sectional study. Chi-square test and ordinal logistic regression analysis were used to examine the relationship between adherence to nutrition-related cancer prevention guidelines and potential predictors of adherence.ResultsMajority of the survivors met the guideline for red and processed meat (n=191, 83.4%), but did not meet the guideline for fruits and vegetables (n=189, 80.4%). For survivors with annual household incomes < $25,000, the odds of meeting or partially meeting the guideline for fruits and vegetables was 75.4% less than for participants with incomes > $50,000 (OR= 0.25, 95% CI: 0.08, 0.80). Poor physical functioning (OR= 38.48, 95% CI: 2.26, 656.58), sleep disturbances (OR= 60.84, 95% CI: 1.61, 2296.02), and income > $50,000 (OR= 51.02, 95% CI: 1.13, 2311.70) were associated with meeting the guideline for red and processed meat.ConclusionsMany AA breast cancer survivors are not meeting the nutrition-related cancer prevention guidelines. For this population, more interventions that enhance access to and consumption of healthy diets are needed.

Hot Spot Mutation in TP53 (R248Q) Causes Oncogenic Gain-of-Function Phenotypes in a Breast Cancer Cell Line Derived from an African American patient.

African American (AA) breast cancer patients often have triple negative breast cancer (TNBC) that contains mutations in the TP53 gene. The point mutations at amino acid residues R273 and R248 both result in oncogenic gain-of-function (GOF) phenotypes. Expression of mutant p53 (mtp53) R273H associates with increased cell elasticity, survival under serum deprivation conditions, and increased Poly (ADP ribose) polymerase 1 (PARP1) on the chromatin in the AA-derived TNBC breast cancer cell line MDA-MB-468. We hypothesized that GOF mtp53 R248Q expression could stimulate a similar phenotype in the AA-derived TNBC cell line HCC70. To test this hypothesis we depleted the R248Q protein in the HCC70 cell line using shRNA-mediated knockdown. Using impedance-based real-time analysis we correlated the expression of mtp53 R248Q with increased cell deformability. We also documented that depletion of mtp53 R248Q increased PARP1 in the cytoplasm and decreased PARP1 on the chromatin. We conclude that in the AA-derived TNBC HCC70 cells mtp53 R248Q expression results in a causative tumor associated phenotype. This study supports using the biological markers of high expression of mtp53 R273H or R248Q as additional diagnostics for TNBC resistant subtypes often found in the AA community. Each mtp53 protein must be considered separately and this work adds R248Q to the increasing list of p53 mutations that can be used for diagnostics and drug targeting. Here we report that when R248Q mtp53 proteins are expressed in TNBC, then targeting the gain-of-function pathways may improve treatment efficacy.

A Community-Based Exercise and Support Group Program Improves Quality of Life in African-American Breast Cancer Survivors: A Quantitative and Qualitative Analysis.

African-American (AA) breast cancer (BCa) survivors have higher mortality rates, more comorbidities and are less likely to meet national physical activity guidelines after diagnosis compared to Caucasian BCa survivors. We previously reported that a 20-week resistance exercise intervention coupled with a support group and home walking program, conducted using facilities and personnel at a community cancer support center, in Stage I-III AA BCa survivors improved strength, fitness and circulating C-peptide levels. Here, we report our findings on changes in quality of life (QoL) and other behavioral measures associated with this 20-week intervention and, discuss findings from a qualitative analysis of semi-structured patient interviews. We found a clinically relevant improvement in QoL using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) (Baseline, B: 101.1 ± 21.5; End-of-Intervention, EOI: 108.5 ± 21.6; p = 0.05) and, a significant decrease in depression using the Beck Depression Inventory-II (B: 11.9 ± 8.1; EOI: 9.0 ± 5.5; p = 0.03). Our analysis of the patient interviews support improvements in these behavioral measures in that participants stated that they "feel better", were "more motivated" and "uplifted" after the program. The patient interviews also provided insights to the primary motivators (e.g., social support, improvements in strength and function, weight loss) and barriers (e.g., family and health issues) in adhering to the program and provided suggestions for improving the program (e.g., incorporating nutritional and treatment related side-effect discussions). Our results suggest that community-based lifestyle interventions may improve QoL and depression in AA BCa survivors and lend insights for improving future programs.

Weight loss with mindful eating in African American women following treatment for breast cancer: a longitudinal study.

Women with higher body mass index (BMI) following breast cancer (BC) treatment are at higher risk of BC recurrence and death than women of normal weight. African American (AA) BC patients have the highest risk of BC recurrence and gain more weight after diagnosis than their white counterparts. The purpose of this study was to evaluate the association between a mindful eating intervention and weight loss in AA women following chemotherapy for BC. A single-group 24-week longitudinal pilot study with repeated measures was conducted. AA women (N = 22, BMI = 35.13 kg/m(2), range = 27.08-47.21) with stage I-III BC who had finished active cancer treatment received a 12-week mindful eating intervention with individual dietary counseling and group mindfulness sessions, followed by bi-weekly telephone follow-up for 12 weeks. Linear mixed models were used to evaluate the effects of the intervention and of baseline mindfulness on the weight change over time. In the overall group (N = 22), MEQ scores increased over time (p = 0.001) while weight decreased over time (-0.887 kg, p = 0.015). Weight loss over time was associated with higher T1 MEQ scores (p = 0.043). Participants in the higher MEQ group (n = 11) at T1 experienced significant weight loss over time (-1.166 kg, p = 0.044), whereas those in the low MEQ (n = 11) did not lose weight. Participants who were diagnosed with stage 1 BC experienced significant weight loss over time (-7.909 kg, p = 0.014). This study suggests that a mindful weight loss program may be effective for weight reduction and maintenance in some AA women who have completed treatment for BC, particularly those diagnosed with stage 1 BC and with initially higher mindful eating behaviors. Mindful weight loss program is proposed as a promising way in which to reduce obesity-related conditions in AA BC survivors.

Abstract PR13: Disparities in centrosomal profiles: Prediction of metastatic risk in African American and European American breast cancer patients

Abstract Centrosome amplification has long been established as a hallmark of cancer. More than 80% of invasive breast tumors display this cellular trait. Centrosomal aberrations underlie chromosome instability (CIN) thus corroborating the extensive clonal intratumoral heterogeneity existent within breast lesions that fuels tumor evolution. Sub-clonal heterogeneity drives emergence of aggressive clones with a propensity to migrate and invade, resulting in tumor dissemination and metastases. Thus, centrosome amplification is a critical driver of tumor progression and metastases. Although numerous studies have linked centrosomal overload to tumor aggressiveness, no studies have yet quantified this cell-biological feature to establish a well-defined relationship between the severity and extent of centrosome amplification and tumor aggressiveness. Utilizing an innovative and rationally-guided approach, we have derived an algorithm that allows the precise quantitation of the frequency and severity of both structural and numerical aberrations in supernumerary centrosomes present in clinical samples. Our novel method thus uncovers previously unrecognized differences in the centrosomal profiles of grade-matched breast tumors from African-American (AA) (n=71) and European American (EA) (n=104) women. Our data demonstrate that AA breast tumors exhibit higher numeral, structural and total centrosome amplification scores than grade-matched EA tumors. Interestingly, tumors displaying lymph node and distant metastasis exhibited higher structural amplification than grade-matched non-metastatic tumors. Hence, our novel quantification tool offers valuable information that can potentially predict the risk of AA breast tumors rapidly progressing to metastatic disease and uncovers a hitherto unappreciated organelle-specific disparity marker among racially distinct breast tumors. This abstract was also presented as Poster B6. Citation Format: Nikita Wright, Vaishali Pannu, Padmashree Rida, Karuna Mittal, Sergey Klimov, Farida N. Yada, Michelle D. Reid, Guilherme Cantuaria, Ritu Aneja. Disparities in centrosomal profiles: Prediction of metastatic risk in African American and European American breast cancer patients. [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 PR13.

Abstract A76: MicroRNA mediated negative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities

Abstract Although rates of breast cancer incidence are lower in African American (AA) women, the mortality rates are significantly higher compared to non-Hispanic white (WNH) women. This shocking statistic illustrates the racial disparities in breast cancer, as AA women have a poorer prognosis compared to WNH women. While this may be due in part to socioeconomic and standard of care issues, increasing evidence suggests that the racial disparity exists independent of these issues and could also be attributed to poorly understood inherent genetic and molecular characteristics within racial specific tumors. Caveolin-1 (Cav1) is a scaffolding protein with a tumor suppressor role. Loss of Cav1 in the tumor stromal compartment has emerged as a novel biomarker for predicting poor clinical outcome in all of the most common subtypes of human breast cancer, including the more lethal triple negative subtype which is significantly more common in AA women. While the loss of stromal Cav1 is becoming well established as a marker of poor outcome in breast cancer, the mechanism of this loss is still unknown. We propose that differences in microRNA mediated stromal Cav1 loss between AA and WNH women is driving the racial disparity in breast cancer. MicroRNAs (miRNAs) are short, endogenous, non-coding RNA that function as negative regulators of gene expression. miR-510 is an oncogenic miRNA that has been shown to be elevated in breast tumors. Cav1 is a predicted target of miR-510 and therefore miR-510 mediated negative regulation may be a novel mechanism of Cav1 loss in the tumor stroma. Our research shows that Cav1 is directly targeted by miR-510 by luciferase reporter assay and that overexpression of miR-510 leads to downregulation of Cav1 protein expression, specifically in the stromal compartment. Tumor epithelium and stroma co-culture assays demonstrate that epithelial derived miR-510 may be transferred to neighboring stromal cells and negatively regulate Cav1 expression in the stromal compartment. This may be racially significant as our supporting studies also show that miR-510 levels are elevated and Cav1 levels are reduced in AA breast cancer patients compared to their white counterparts. Our results suggest that the difference in miR-510 mediated regulation of stromal Cav1 is driving racial disparity in breast cancer. Citation Format: Qi Jin Guo, Brooke King, Bobbie Blake, Amanda C. LaRue, Judith D. Salley, Marvella E. Ford, Ashley Evans-Knowell, Victoria J. Findlay. MicroRNA mediated negative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities. [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 A76.

Abstract PR08: Chemotherapy modification by race in early breast cancer treatment

Abstract Introduction: African American (AA) women are less likely to receive recommended standard treatment or discontinue treatment early for their breast cancer in comparison to white women. Dose reductions and delays during breast cancer chemotherapy can negatively affect survival. The purpose of this study was to examine racial differences in chemotherapy dose modifications among early stage breast cancer patients. We also explored the role of neutropenia in explaining these differences. Methods: Patients were selected from the Breast Cancer Treatment Disparity Study that is composed of AA and white women from New Jersey who were diagnosed with stage I, II, and T3N1M0 breast cancer between 2005-2010, with no prior history of cancer, and age ≤ 85 years. Patients who received chemotherapy as part of their breast cancer treatment were included. Detailed data on chemotherapy administration was abstracted from patient medical records. Chemotherapy dose delivered was measured using relative dose intensity (RDI), defined as the amount of drug delivered per unit time expressed as a fraction of expected dose intensity of a standard regimen. The National Cancer Comprehensive Network Guidelines were used for reference (expected) values of chemotherapy dose and schedule. RDI captures modifications resulting from both delays in administration or reduction in dose and it was computed for the entire course of therapy as well as for each cycle delivered. Racial differences in the mean RDI delivered (per subject and per cycle) and risk of &amp;gt;15% reduction in RDI (per subject) were examined using repeated measures linear and binomial regression models, respectively. The models were adjusted for white blood cell (WBC) level during chemotherapy. Results: The study included 143 AA and 145 white patients (with a total of 2063 chemotherapy cycles). The majority of patients received adjuvant chemotherapy (white= 93.1%, AA= 91.6%) and the remaining received neoadjuvant chemotherapy (white= 6.9%, AA= 8.4%) with no differences by race. Commonly administered regimens were dose-dense doxorubicin/cyclophosphamide followed by paclitaxel every two weeks (AA= 25.2%, white= 32.4%), docetaxel/cyclophosphamide every three weeks (AA= 23.1%, white= 17.2%), doxorubicin/cyclophosphamide every three weeks (AA= 11.9%, white= 12.4%), and doxorubicin/cyclophosphamide followed by weekly paclitaxel (AA= 9.8%, white= 13.1%). Receipt of anthracycline-based regimen was similar between AAs and whites (67.1% and 69.7%, respectively), as was addition of taxanes to anthracycline-based regimen (AA= 82.3%, white= 80.2%). A higher proportion of AA patients (10.5%) did not complete the recommended number of cycles in comparison to whites (5.5%), though the difference was not statistically significant (p= 0.120). Mean RDI per subject was 94.4% for AAs and 100.0% for whites (difference= −5.62%, p= 0.005). After adjusting for WBC level during chemotherapy, the mean RDI difference was −5.29% (p= 0.009). When RDI per cycle was examined, the mean unadjusted and adjusted RDI difference between AAs and whites were −8.27% (p&amp;lt; 0.001) and −7.92% (p&amp;lt; 0.001), respectively. The proportion of patients with &amp;gt;15% reduction in RDI was more than twice among AAs than whites (21.7% versus 8.3%, p=0.001). The unadjusted risk of &amp;gt;15% reduction in RDI was 2.62 (95% CI: 1.40, 4.89) in AA women as compared to white women; and was 2.50 (95% CI: 1.33, 4.70) after adjusting for WBC level. Conclusions: We found that AA breast cancer patients were significantly more likely to receive a reduced dose of chemotherapy as compared to white patients. WBC levels during the course of chemotherapy did not explain the racial disparity in chemotherapy dose reduction. The reasons for dose reduction in AA breast cancer patients merit investigation. This abstract was also presented as Poster A91. Citation Format: Sheenu A. Chandwani, Kim M. Hirshfield, Adana A. Llanos, Elisa V. Bandera, Yong Lin, George G. Rhoads, Kitaw Demissie. Chemotherapy modification by race in early breast cancer treatment. [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 PR08.

1704 Lymphedema signs, symptoms, self-reported diagnosis and referral to physical therapy among African American and low-income breast cancer survivors

1704 Lymphedema signs, symptoms, self-reported diagnosis and referral to physical therapy among African American and low-income breast cancer survivors

Abstract 4834: Single cell multiplex gene expression analysis to unravel heterogeneity of PDX samples established from tumors of breast cancer patients with different ethnicity

Abstract Intra-tumor heterogeneity represents one of the main challenges in cancer therapeutics. This heterogeneity is generated at the genetic level primarily by genomic alterations and clonal selection and at the epigenetic level by tumor cell differentiation. In addition, inter-tumor heterogeneities may also be related to differences in tumor biology in different ethnic populations. To explore the cell heterogeneity in breast cancer, we studied patient derived xenograft (PDX) models generated from African (Ghana), African-American, and Caucasian breast cancer patients. Gene expression of a selected panel of cancer associated genes was determined in single cells using C1 and BioMark HD platforms. Analyzed multiplex RT-qPCR data revealed significant heterogeneity in mRNA expression within and between studied PDX samples at single cell resolution. We observed a significantly different mRNA expression profile within each ethnic group of breast cancer PDX samples. In addition, distinct gene expression signatures were observed between the PDX samples of different ethnic origin. ALDH1a1, ALDH1a3, CD44, CD24, and CD133 were among the CSC markers that were differentially expressed in different PDX single cell samples. Vimentin, EpCAM, HER2, CDH1, CDH2, TGFb1, cytokeratins, GATA3 and MKI67 genes related to the epithelial to mesenchymal (EMT) and mesenchymal to epithelial (MET) phenotypes also demonstrated significantly variable expression in the studied PDX samples. YAP1, TM4SF1, TSPAN6, AMOTL2, STAP2 and ANXA3 genes were differentially expressed in the PDX samples. These candidate biomarkers represent a collection of genes that may warrant further investigation for their potential involvement in cancer initiation, promotion and progression to metastasis, and drug resistance. These data emphasize the importance of studying tumors at single cell resolution to unravel gene expression variation. Upon validation in clinical tumor specimens, this approach could help to identify cellular subpopulations within tumors and possibly identify novel targets for cancer therapy. Citation Format: Ebrahim Azizi, Evelyn M. Jiagge, Shamileh Fouladdel, Shukmei Wong, Michele L. Dziubinski, Mary Sehl, Anahita Kyani, Jun Li, Hui Jiang, Tahra K. Luther, Shawn G. Clouthier, Sean P. McDermott, John Carpten, Lisa A. Newman, Sofia D. Merajver, Max S. Wicha. Single cell multiplex gene expression analysis to unravel heterogeneity of PDX samples established from tumors of breast cancer patients with different ethnicity. [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 4834. doi:10.1158/1538-7445.AM2015-4834

Abstract 1300: Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study

Abstract The tumor microenvironment is a complex biosystem composed of diverse cells, including tumor, immune and non-immune stromal cells. It has become increasingly clear that stromal cells have critical roles in tumor progression. Among the immune stromal cells, tumor-associated macrophages (TAM) are found in abundance, playing critical roles in tumor progression and are signs of poor prognosis. Whereas in chronic inflammation of a tissue M1 pro-inflammatory macrophages may play a role in tumor initiation, in advanced tumors, TAMs promote anti-inflammatory functions including suppression of immunity, tumor invasion, angiogenesis, metastasis, and resemble the behavior of M2 anti-inflammatory macrophages. CD163 is considered a human pan macrophage marker and has been extensively used in TAMs recognition in human tumors. Until recently, macrophages were considered end-differentiated cells without mitotic activity. However, more recently proliferative activity of macrophages has been identified in several settings, but not in tumors. In a recent study, we demonstrated that breast cancers from different ethnicities exhibit diverse degree of TAMs colonization. African American (AA) and Latina (LA) patients present with more aggressive tumors and lower survival rates than Caucasian (CA) women. We recently demonstrated that AA breast cancer patients exhibit tumors with very high numbers of macrophages, followed by LA, with CA showing the lowest numbers of TAMs. Consequently, in the present study we sought to examine whether the high numbers of TAMs detected in these cancer health disparity groups were associated with macrophage capacity to proliferate. To assess TAM mitotic potential, the Ki-67 nuclear marker was used. To examine this question, we carried out a pilot study with a small number of cases where the co-expression levels of Ki-67 and CD163 were determined by immunofluorescence (IF) in sections of human breast cancers from a retrospective breast cancer tumor bank encompassing these three ethnicities. Our results reveal that tumors from AA patients contain the highest numbers of CD163+/Ki-67+ cells among the three ethnic groups, followed by LA, with CA exhibiting the lowest numbers, thus paralleling our results with TAM numbers in these same ethnicities. As far as we know, this is the first report of macrophage proliferation in a tumor microenvironment, and particularly in association with ethnicity cancer disparity groups. Citation Format: Lidia G. Sanchez, Jorge E. Torrez-Munoz, Ana M. Santander, Tan A. Ince, Marta Torroella-Kouri. Breast cancer-associated macrophages undergo proliferation at different rates across ethnicities: results of a pilot study. [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 1300. doi:10.1158/1538-7445.AM2015-1300

Abstract 1258: The unfolded protein response may contribute to racial disparity in endocrine responsiveness in breast cancer

Abstract About 70% of all breast cancers are estrogen receptor alpha positive (ER+) and depend on estrogen to grow and proliferate. Anti-hormone therapy such as antiestrogens (e.g., Tamoxifen; TAM) are often used to treat ER+ breast tumors but the cancer cells can develop resistance to these drugs (endocrine resistance). Unfortunately, ∼50% percent of all antiestrogen treated tumors eventually develop endocrine resistance, and therefore, there is an urgent need to find ways to treat this incurable disease. Nonetheless, little is known about the causes of endocrine resistance, and even less is known about the racial disparities that exist for antiestrogen responsiveness among ER+ breast cancer cases. Clinical investigations into ER+ breast cancer cases with similarly treated tumors showed that progression-free survival (PFS) and overall survival (OS) in African-American (AA) women were worse than in European-American (EA) women. The underlying causes of these racial differences within ER+ breast cancers is unknown. One cellular adaptive mechanism that allow endocrine resistant cells to survive antiestrogen treatment is a called the unfolded protein response (UPR) that is initiated within the endoplasmic reticulum caused by a stress stimulus. Cellular stress induced by antiestrogens can trigger the UPR leading to induce a pro-survival response by inhibiting cell death (by apoptosis) and promoting cell survival (by autophagy). Gene expression analysis for ER+ tumors of AA patients show up-regulation of UPR genes such as glucose-regulated protein 78, GRP78 (also known as HSP5A or BiP), activation transcription factor-6 (ATF6) and spliced X-box-protein-1 (XBP1s). Moreover, ER+ breast cancer cell lines derived from tumors of AA patients show increased levels of GRP78, ATF6 and XBP1 compared with cells derived from EA patients. The ER+ breast cancer cell lines derived from tumors of AA patients also show reduced sensitivity to Tamoxifen compared with cells derived from EA patients. Through our study, we will determine how up-regulation of the UPR contribute to the differences noted in anti-hormone therapy in treatment of ER+ breast cancer in AA versus EA women. Therefore, targeting critical pro-survival signaling molecules of the UPR can inhibit endocrine resistance and reduce growth of ER+ breast cancer cells more efficiently and avoid unsuccessful treatment in AA breast cancer patients. Citation Format: Ahreej E. Eltayeb, Diane M. Demas, Robert Clarke, Ayesha N. Shajahan-Haq. The unfolded protein response may contribute to racial disparity in endocrine responsiveness in breast cancer. [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 1258. doi:10.1158/1538-7445.AM2015-1258

Abstract P4-11-41: Pretreatment neutrophil/lymphocyte ratio and overall survival in African American and white breast cancer patients

Abstract Previous studies have shown that the pretreatment neutrophil/lymphocyte ratio (NLR) is an independent predictor of mortality in breast cancer patients. Our aim was to further study the relationship between pretreatment NLR and overall survival in African American and white breast cancer patients treated at an academic cancer center. Electronic medical records were reviewed for 589 patients treated between 2002 and 2011, and pretreatment NLR data, determined at an average of 12 days prior to the initiation of cancer treatment, were available from 217 African American and 218 white patients. Other clinical and patient data were obtained from the hospital tumor registry, with annual follow-up for vital status. There were a total of 102 deaths over a mean follow-up of 59 months. For data analysis, patients were divided into quartiles based on their NLR (Q1: &amp;lt;1.54; Q2: 1.54≤2.0; Q3: 2.0≤2.79; and Q4: ≥ 2.79). Patients in the highest quartile of pretreatment NLR showed an increase in overall mortality compared to those in the lowest quartile, with a hazard ratio (HR) of 2.4 (p&amp;lt;0.005). After adjustment for age, tumor stage, and grade, the pretreatment NLR remained significantly associated with overall mortality (HR=2.1, p=0.03). Further adjustment for race, body mass index (BMI) and smoking increased the effect size (HR=3.2, p&amp;lt;0.01), but only half patients remained in the analysis due to incomplete data on BMI and smoking. In our study, race, but neither BMI nor smoking, was associated with pretreatment NLR values: African American patients had higher pretreatment NLR values than white patients regardless of stage. In a stratified analysis by race, HRs for overall mortality associated with the highest quartile of pretreatment NLR versus the remaining three quartiles combined were 2.5 (p&amp;lt;0.01) among African Americans and 1.6 (p=0.24) among white patients, although the interaction between race and pretreatment NLR was not statistically significant. Our data confirm previous findings that pretreatment NLR, a marker of systemic inflammatory response, is unfavorably associated with overall survival in breast cancer patients, and also suggest that the association may be more evident among African American patients whose levels were generally higher than white breast cancer patients. Future studies are warranted to investigate the prognostic utility of pretreatment NLR in different racial groups and whether a heightened systemic inflammatory response is an underlying contributor to racial difference in breast cancer outcomes. Citation Format: Joseph C Rimando, Jeff Campbell, Jae Hee Kim, Sangmi Kim. Pretreatment neutrophil/lymphocyte ratio and overall survival in African American and white breast cancer patients [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 P4-11-41.

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.

Abstract P2-12-10: Examining diagnostic and therapeutic delays using patient reported outcomes

Abstract Background: Diagnostic and treatment delays in cancer patients lead to poorer outcomes. African American and Latina women with breast cancer (BC) are more likely to experience delays. This study explores delays in African American and Latina breast cancer survivors (BCS) and association with physician-patient communication variables. Methods: A total of 320 BCS (88 African-American and 232 Latina-American)diagnosed with stage 0-3 BC were recruited from the California Cancer Registry and Hospitals. BCS completed a questionnaire assessing patient reported time to diagnosis and initiating treatment, and quality of care variables pertaining to physician-patient interaction. Results: The mean number of days waited after finding a lump or abnormality and seeking diagnostic care to obtaining a cancer diagnosis was 57.9 days in this cohort. Bivariate analysis revealed that Latina BCS were significantly more likely to wait longer to obtain diagnosis. ( p = .033). Once diagnosed, African-American BCS were more likely to report greater days delay to initiating treatment (p = .007). The mean number of days delayed for initiating treatment between African American and Latinas, however, was not significantly different, 35.3 v. 34.5 days (p=.107). We investigated the surgeon-patient dyad in influencing delays. The better patients rated the relationship, the fewer days in delayed treatment reported (p=0.038). Additionally, 11% of BCS (n=34) did not believe that their doctors gave them enough information regarding their treatment. The regression analysis showed that the patients’ evaluation of the adequacy of doctors’ information was a significant predictor of days delayed treatment (p&amp;lt;0.0001). If the patient believed that enough information was provided, then the treatment was initiated within 6 days compared to the 40 days average reported by patients who endorse inadequate information. However, the majority of patients (87%) reported a "good" or "very good" relationship with her surgeon. Although the majority of patients reported a "good" or "very good" relationship with her Oncologist (65%), the relationship was rated as "poor" or "very poor" by 23% of patients. There was no statistical difference in rating of relationship with providers between the ethnic groups (p=.865). Conclusions: Our results suggest that poor patient-physician interactions are associated with BC diagnostic and therapeutic care delays in both African American and Latina BCS. As healthcare shifts towards improving variables of quality of care and patient satisfaction, attention to improving these interactions and further exploration will be warranted. Further, improving timely access to diagnostic and therapeutic care may reduce BC disparity and improve cancer equity. Citation Format: Odicie Fielder-Kimbrough, Mayra Serrano, Kimlin T Ashing. Examining diagnostic and therapeutic delays using patient reported outcomes [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 P2-12-10.

Abstract P4-14-07: Understanding disparities in breast cancer care in Memphis, Tennessee

Abstract Background: Recent literature highlights the troubling racial divide in breast cancer mortality that continues to widen in most major cities across the country. Although significant progress has been made in improving overall breast cancer survival, disparities among racial, ethnic, and underserved groups still exist. Previous studies examine the breast cancer mortality disparity in the 50 largest U.S. cities, and Memphis demonstrates the largest breast cancer mortality disparity for African Americans (AA). The goal of this investigation is to quantify racial disparities in the context of breast cancer treatment in order to reduce disparities in recurrence and mortality for breast cancer in the city of Memphis, Tennessee. Methods: Patients with a biopsy- proven diagnosis of breast cancer over a 10 year period ending December 31, 2012 were obtained from the tumor registry of a university hospital system. Females of Caucasian and African-American race were included, while males, patients less than eighteen years of age, and patients with unknown histology, clinical stage, or type of surgery were excluded. Primary outcomes measured included overall survival and recurrence. Secondary outcomes examined were stage at diagnosis by race and time from diagnosis to surgery. Results: 3072 breast cancer patients were reviewed (41% AA). AA patients were more likely to have advanced (Stages II, III, or IV) clinical stage of breast cancer at diagnosis versus Caucasian patients. Of the 113 recurrences, 62% occurred in AA. Of the 676 deaths, 54% occurred in AA. After adjusting for race and clinical stage of breast cancer, AA breast cancer patients had a 2.0 higher odds of recurrence when compared to Caucasian breast cancer patients (95% CI 1.4, 3.0). AA breast cancer patients were 1.5 more likely to die compared to Caucasian breast cancer patients (95% CI: 1.2, 1.8), after adjusting for race, age at diagnosis, clinical stage of breast cancer, ER, PR, and HER2 status, and recurrence. AA women with stages 0, I, II, and III breast cancer all had a statistically significant longer median time from diagnosis to surgery (TDS) than Caucasian women. Conclusions: African-American patients were more likely to have advanced clinical stages of breast cancer at diagnosis versus Caucasian patients on a citywide level in Memphis. African-American breast cancer patients have a higher odds of recurrence and mortality when compared to Caucasian breast cancer patients, after adjusting for appropriate demographic and clinical attributes. Several factors have been suggested for the disparities including racial differences in access to and utilization of screening and treatment, risk factors distributed by race and socioeconomic status (SES), biological differences such as tumor aggressiveness, and cultural factors. More work is needed to develop, evaluate, and disseminate interventions to decrease inequities in timeliness of care for breast cancer patients. Citation Format: Elena M Paulus, Frances E Pritchard, Simonne S Nouer, Elizabeth A Tolley, Brandon S Boyd, Jesse T Davidson, Gitonga Munene, Martin D Fleming. Understanding disparities in breast cancer care in Memphis, Tennessee [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 P4-14-07.