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Background: Despite increased incidence of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in women at average risk for breast cancer. In addition to BRCA1/2 mutation carriers, patients with estrogen-receptor negative tumors have been examined as a subgroup that may seek to benefit from CPM. In this study, we sought to investigate whether CPM improves survival in patients with triple negative breast cancer (TNBC).Study Design: Survival outcomes were evaluated for all TNBC patients from a multi-institutional database from 1999-2018 at New York Presbyterian - Weill Cornell Medical Center and Henry Ford Health System. Median follow-up time was 44.4 months.Results: 802 TNBC patients were evaluated. The median age was 57 years. 17% patients underwent CPM. Factors associated with CPM were White American race, younger age, presence of lymphovascular invasion (LVI), lack of mammography screen-detection, mastectomy surgery, postoperative adjuvant radiotherapy, and having had genetic testing. A borderline significant trend was observed in improved overall survival among patients undergoing CPM versus those not having CPM (5-year OS 95.1% vs. 85.0%; p = 0.05). Subset analysis of patients younger than 50 years of age at diagnosis demonstrated no improvement in overall survival for patients undergoing CPM versus those that declined CPM (94.3% v. 88.7%; p = 0.21). Conclusion: Our data demonstrate a trend in improved 5-year overall survival in TNBC patients undergoing CPM. However, in patients younger than 50 years at diagnosis, CPM did not confer a survival advantage. Citation Format: Genevieve A Fasano, Solange Bayard, Yalei Chen, Jennifer Marti, Rache Simmons, Alexander Swistel, Jessica Bensenhaver, S David Nathanson, Lindsay Petersen, Erica Proctor, Melissa Davis, Lisa Newman. Does contralateral prophylactic mastectomy improve survival in triple negative breast cancer? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-08.

National comprehensive cancer network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple-negative breast cancer (TNBC) if the tumor is 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data on the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size.We performed a retrospective analysis of survival outcomes of TNBC patients at two academic institutions in the United States from 1999 to 2018. Primary tumor size, histology, and nodal status were based upon surgical pathology. The Kaplan-Meier plot and 5-year unadjusted survival probability were evaluated.Among 282 T1N0 TNBC cases, the status of adjuvant chemotherapy was known for 258. Mean follow-up was 5.3 years. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p 0.0001). On multivariable analysis, factors associated with delivery of adjuvant chemotherapy were tumor size and grade 3 disease. Improved overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% vs. 75.2% p = 0.008) but not T1a (100% vs. 100% p = 0.3778) or T1b (100% vs. 95.8% p = 0.2362) disease.Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in the cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Purpose / Objectives: In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) for the treatment of breast cancer may be associated with a different complication profile than those without macromastia. General complications of BCS followed by RT includes seroma, infection, wound complications, cosmetic deformity, asymmetry, acute versus long term arm and/or breast lymphedema. Oncoplastic reduction mammoplasty (ORM) aims to reduce breast volume while excising the tumor bed and its margins. Since breast volume was found to be a risk factor for chronic breast lymphedema, this study was performed to determine the impact of ORM on chronic breast lymphedema as well as other complications compared to BCS without ORM. Materials / Methods: We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2018. Chronic breast lymphedema (CBL) was defined as swelling that persisted >1 year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to 1300 cc are at increased risk for developing several complications regardless of the presence of ORM. Those who had ORM experienced an increase in wound complications but having undergone ORM appeared to eliminate the increased risk of CBL associated with macromastia. This suggests that ORM should be considered at the time of BCS to reduce their future risk of CBL as there is no cure for this disease. Citation Format: Jenna Nicole Luker, Cara Canella, Sanjay Rama, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Maristella Evangelista, Dunya Atisha. The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-49.

Purpose/Objective(s):Unlike temporary breast edema caused by post-lumpectomy radiation therapy (RT), the edema that persists beyond one year is not well defined and difficult to treat. The aim of this study is to define the incidence and risk factors for the development of chronic breast lymphedema in women undergoing lumpectomy with RT at a large metropolitan cancer center. Materials/Methods:A retrospective chart review was performed on all patients who underwent lumpectomy from 2014 to 2018. Women who did not undergo RT at our institution and those with stage IV disease were excluded from the analysis. Patient demographics, comorbidities, operative data, RT data and postoperative complications were obtained. Chronic breast lymphedema (CBL) was defined as edema that persisted beyond one year post completion of radiation therapy. Breast volumes were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Using a density curve, the distribution of breast volumes was plotted for patients with and patients without CBL. Univariate analysis was used to evaluate factors associated with CBL. Multivariate regression analysis was used to evaluate factors associated with the risk of CBL while accounting for potential confounding variables as defined by the univariate analysis. Results:A total of 1173 patients were included for analysis. Seventy-four (6.3%) patients developed breast lymphedema beyond one year. For the entire cohort, mean age was 63 years old (SD=11.17), mean BMI was 31.15 kg/m2 (SD=7.17), mean breast volume was 1198.54 cm3 (SD=645.82 cm3), mean total radiation was 59.18 Gy (SD=16.76), and 139 (11.8%) patients underwent ALND. Compared to the cohort that did not develop CBL (n=1099), the CBL cohort (n=74) had a higher median BMI (33.23 kg/m2 vs. 29.81 kg/m2, P Conclusion:Chronic breast lymphedema presents a clinical concern for women undergoing lumpectomy with postoperative radiation, particularly in women with larger breasts. Further studies should focus on preventative strategies, as well as the psychosocial and economic impact of this morbidity. Citation Format: Sanjay Rama, Cara Canella, Jenna Luker, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Dunya Atisha, Maristella Evangelista. Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-12.

To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations.Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence.We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC.TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P0.0001). TNBC cases had higher West African ancestry than non-TNBC (P0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P0.0001), quantified West African Ancestry (P0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant.West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

INTRODUCTION: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS: We used the Institute for Healthcare Improvement’s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute’s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P < .01). CONCLUSION: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted.

BACKGROUND Decisions made to undergo contralateral prophylactic mastectomy, in women at low risk for bilateral disease, are often attributed to a lack of knowledge. This study examines the role knowledge plays in determining surgical treatment for unilateral breast cancer made by laywomen and surgeons for themselves or loved ones. METHODS The study cohort had three groups: (1) laywomen in the general population, (2) breast surgeons, and (3) plastic surgeons. Laywomen were recruited using Amazon Mechanical Turk Crowd Sourcing. Breast and plastic surgeons from nine states were sent electronic surveys. Demographic and contralateral prophylactic mastectomy-specific data on decisions and knowledge were collected and analyzed. RESULTS Surveys from 1333 laywomen, 198 plastic surgeons, and 142 breast surgeons were analyzed. A significantly greater proportion of laywomen in the general population favored contralateral prophylactic mastectomy (67 percent) relative to plastic (50 percent) and breast surgeons (26 percent) (p < 0.0001). Breast surgeons who chose contralateral prophylactic mastectomy were younger (p = 0.044) and female (0.012). On assessment of knowledge, 78 percent of laywomen had a low level of breast cancer knowledge. Laywomen with higher levels of breast cancer knowledge had lower odds of choosing contralateral prophylactic mastectomy (OR, 0.37; 95 percent CI, 0.28 to 0.49). CONCLUSIONS Fewer women are likely to make decisions in favor of contralateral prophylactic mastectomy with better breast cancer-specific education. A knowledge gap likely explains the lower rates with which surgeons choose contralateral prophylactic mastectomy for themselves or loved ones; however, some surgeons who were predominantly young and female favor contralateral prophylactic mastectomy. Improving patient education on surgical options for breast cancer treatment is critical, with well-informed decisions as the goal.

We evaluated 328 patients (34.8% African American [AA]; 65.2% White American [WA]) with hormone receptor-positive, HER2/neu-negative breast cancer. Mean age (60 years); mean tumor size (1.6 and 1.7 cm for AA and WA, respectively) were similar, and mean BMI was higher for AA (33 vs 29.8; P = 0.001). Recurrence score (RS) distribution was similar- 8.3% AA and 5.9% WA with high RS (≥31). No significant differences were observed in delivery of chemotherapy stratified by score. With median follow-up 27.2 months for AA and 33.4 months for WA, distant recurrence occurred in 1.0% and 1.6%, respectively (P = 1). Our results suggest comparable RS utility in AA and WA patients.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case–control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

BACKGROUND Breast cancer mortality rates are 39% higher in the African-American (AA) women compared to White-American (WA) women despite the advances in overall breast cancer screening and treatments. Several studies have undertaken to identify the factors leading to this disparity in United States with possible effects of lower socioeconomic status and underlying aggressive biology. METHODS A retrospective analysis was done using a prospectively maintained database of a metropolitan health system. Patients were selected based on diagnosis of early-stage breast cancer between 10/1998 and 02/2017, and included women over age of 18 with clinically node-negative disease. Patients were then stratified by phenotype confirmed by pathology and patient-identified race. RESULTS A total of 2,298 women were identified in the cohort with 39% AA and 61% WA women. The overall mean age at the time of diagnosis for AA women was slightly younger at 60 years compared to 62 years for WA women (p = 0.003). Follow-up time was longer for the WA women at 95 months vs. 86 months in AA women. The overall 5-year survival was analyzed for the entire cohort, with the lowest survival occurring in patients with triple-negative breast cancer (TNBC). Phenotype distribution revealed a higher incidence of TNBC in AA women compared to WA women (AA 16% vs. WA 10%; p

DARC/ACKR1 erythrocyte expression, also known as the “Duffy blood group,” is understood to sequester pro-inflammatory chemokines and thereby regulate circulating gradients that direct immune cell infiltration. We hypothesize that this function also determines immune cell landscapes in the tumor microenvironment. Due to evolutionary selection pressures of malaria, individuals with sub-Saharan African ancestry typically carry the Duffy-null allele (rs4849887) and this lack of DARC/ACKR1 expression gives immunity to malaria while also allowing chronically high inflammation levels. Over 68% of African Americans (AA) have been found to have the Duffy-null genotype, compared to a rare 1-3% in European American individuals and we have shown it increases predisposition for Triple-Negative Breast Cancer (TNBC). In addition, we are currently studying if Duffy-null may contribute to higher breast cancer mortality that disproportionately affects AA women. This may be in part due to the role that low-DARC/ACKR1 expression plays in chronic inflammation, altering levels of several chemokines that modulate the migration and differentiation of specific immune cells. This role will impact tumor immune cell infiltration as well as the immune cell population composition overall, depending upon levels of DARC/ACKR1. Using RNA sequencing, our initial results indicated that for breast cancer tumors with high DARC/ACKR1 expression there was a higher estimated presence of CD8+ T cells, CD4+ T cells, regulatory T cells, follicular helper T cells, and memory B cells. Whereas with low DARC/ACKR1 expression, there was markedly less expression of resting dendritic cells and memory B cells. Therefore, in order to ascertain the influence DARC status has on spatial deposition and functional status of immune cell landscapes across the tumor microenvironment, we performed imaging mass cytometry on primary TNBC tumors. The panel contained tumor, structural, and immune markers, and was used to characterize the spatial differences between samples that had been verified to be DARC-high or DARC-low through immunohistochemistry. Our imaging analyses indicated that high DARC/ACKR1 expression correlates with infiltration of monocytes, macrophages, and cytotoxic T cells into the solid tumor microenvironment. Conversely, tumors with low DARC/ACKR1 expression showed monocytes and cytotoxic T cells contained in the tumor stroma. Using single-cell phenotyping, we were also able to identify distinct cell populations between DARC-high and -low. The tSNE analysis and heatmaps performed using Histology Topography Cytometry Analysis Toolbox (histoCAT), allowed us to visualize the spatial distribution of these cell populations, indicating an immune-suppressive tumor microenvironment in DARC-low tumors. These differences may be implicated in the causality of tumor progression as well as how to approach treatment given the cell heterogeneity of TNBC. This work provides greater context on the role that Duffy-null plays in chronic inflammation on the tumor microenvironment. Citation Format: Yanira Guerra, Rachel Martini, Jessica Bensenhaver, Yalei Chen, Joseph K. Oppong, Ishmael Kyei, Frances S. Aitpillah, Michael O. Adinku, Joseph K. Oppong, Ernest K. Adjei, Aisha Jibril, Baffour Awuah, Mahteme Bekele, Engida Abebe, Kwasi Ankomah, Ernest B. Osei-Bonsu, Kofi K. Gyan, Clayton Yates, Kim Blenman, Olivier Elemento, Lisa Newman, Melissa B. Davis. The role of African Duffy-null allele related inflammation on the tumor microenvironment [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-141.

Rarity of male breast cancer limits available clinical research and data for management guidance and screening guidelines for patients at high risk. Here, we report on a patient with bilateral, synchronous male breast cancer with discussion of risk factors and need for possible screening.

10591 Background: TNBC is disproportionately prevalent in African American (AA) populations and in women with BRCA-1 germline mutations. BRCA mutation carriers are candidates for targeted therapy with PARP-inhibitors, and testing results may influence risk-reducing surgery choice. Methods: We evaluated genetic testing patterns and outcomes for TNBC patients treated in the prospectively maintained databases of academic cancer programs in two metropolitan cities in the Northeast (New York City, NYC) and Midwest (Detroit, Det), 1998-2018. Median follow up was 3.73 years. Testing patterns were also analyzed by time, comparing pts diagnosed before versus after the mid-2013 Supreme Court ruling that expanded testing availability by banning gene patenting. Results: Of 810 pts, 600 were from NYC and 200 from Det; 202 were AA and 488 WA. Pts undergoing genetic testing were younger (median age 50 vs 62; p < 0.0001). Compared to WA, AA pts were less likely to undergo genetic testing overall (23.8% vs 42.0%; p < 0.0001) and within site (NYC: 25.6% vs 42.8%, p = 0.008; Det: 22.3% vs 38.6%, p = 0.025). No significant differences were seen in frequency of pathogenic BRCA mutations (AA-14.6%; WA-29.3%) or VUSs (AA-6.3%; WA- 4.9%); p = 0.20. Genetic testing disparities were reduced among pts diagnosed after mid-2013 (AA-31.4% vs WA-44.0%; p = 0.01) compared to pre-mid-2013 (AA-18.3% vs WA-40.7%; p < 0.0001). No differences were seen in local or distant recurrence free survival between patients with BRCA, BRCA variants of uncertain significance, non-BRCA mutations, and patients without genetic mutations (local recurrence p = 0.827; distant recurrence p = 0.574). This outcome equivalence was consistent when stratified by WA vs AA identity. Conclusions: Genetic testing has increased for TNBC pts following the mid-2013 Supreme Court ban on gene patenting, but race-associated disparities persist. Pts undergoing genetic testing are more likely to undergo risk-reducing mastectomy, but testing results do not affect survival outcomes, regardless of race. Addressing genetic testing disparities will become increasingly important as mutation-associated targeted therapies are identified through advances in precision medicine.

Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. Invasive BC diagnosed 1998–2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul’s Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p

Introduction In sub-Saharan Africa, breast cancer (BC) is the leading cancer in women and the second cause of cancer mortality. In order to reduce the burden of BC in women with African ancestry there is a need for a structured, coordinated effort to address gaps in our understanding of the factors associated with the disease that influence tumor initiation, progression, and outcomes. To address this need ‘Precision Medicine for African Breast Cancer (PMABC)’ a comprehensive partnership housed at the Henry Ford Cancer Institute was created with the aim of bringing together African researchers to study African BC. We are currently composed of nine leading institutions spanning West and East Africa and two institutions in the United States. Objectives The broad aim of PMABC is to bring together researchers and institutions across sub-Saharan Africa to partner with foreign institutions and funding agencies to study and identify new and improved methods of screening, diagnosing, and treating BC in Africans to improve the overall outcome. Among the aims of PMABC are: • Registry: Create a national BC registry building on data from participating institutions which comprise at least 80% of all BC cases seen in the respective country • Standardization of pathology protocol and reporting: harmonize the pathology reporting scheme and ensure its conformity to international standards Standardization of treatment protocols: Study and compare treatment protocols with international standards and make recommendations • Biorepository: Create a national repository of patient samples to be used in genetic and biological studies • Study African tumor biology: Build the capacity to be able to study African tumors locally and participate in clinical trials • Patient follow up and survival studies: study and obtain data on patient outcomes Achievements We currently have ethical approval and have begun work in nine institutions across West and East Africa. • Creation of a national database in Ghana that currently consists of over 7000 patients. The data is being analyzed to determine risk factors and the distribution of BC by subtypes • We are setting up two research labs in Ghana to train local researchers for basic and translational research • We have a biorepository of over 2000 patient samples that is available for collaborative studies • We have developed tumor models from continental African breast tumors • Building partnership with international organizations, pharmaceutical companies, and funding agencies to study African BC Conclusion PMABC serves as an umbrella institution to coordinate the work between these researchers and to provide resources for the institutions to provide a high level of BC research and treatment. We are aiming to partner with countries across Africa to translate the model created by PMABC in order fulfill the need for further BC research and standardization of data collection and treatment. PMABC is made possible because of the dedication and passion of our collaborating researchers. Citation Format: Sabrina I. Fossi, Sylvester Antwi, Kwabena Agbedinu, Kafui Akakpo, Samuel Mensah, Nelson Affram, Mohammed Sheriff, Foster Amponsah, Jacqueline Asibey, Osei Collins, Alex Mremi, Livingstone Aduse-Poku, Kurt Fernando, Haythem Ali, Eleanor Walker, Jessica Bensenhaver, Evelyn M. Jiagge. Precision medicine for African breast cancer: Bringing African researchers together to study African breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-189.

The Duffy Antigen Receptor for Chemokines (DARC/ACKR1) is an atypical chemokine receptor which promiscuously binds chemokines of both CC and CXC chemokine families. DARC/ACKR1 maintains homeostatic levels of chemokines in circulation through its expression on erythrocytes, and in tissues participates in chemokine transport, where chemokines are transported across the cell layer to help establish chemokine gradients. Establishment of these chemokine gradients is essential for proper immune cell trafficking. In our recent study, we have shown that DARC/ACKR1 is expressed on the tumor epithelium, and through in silico analysis of data from the Cancer Genome Atlas (TCGA), that higher DARC/ACKR1 expression is positively and significantly correlated with tumor-associated leukocyte abundance when using CIBERSORT deconvolution methods. Specifically, higher DARC/ACKR1 expression was linked with increases in B cell, T cell, monocyte and macrophage populations. Higher DARC/ACKR1 expression is also significantly associated with better survival outcomes, across all breast cancer molecular subtypes. To further evaluate DARC/ACKR1 expression and influences on the breast TME, we have employed multiple approaches to characterize how DARC/ACKR1 impacts immune cell recruitment and subsequent infiltration into the tumor. In our patient cohort, we have recently completed Hyperion imaging mass cytometry staining of tumors that have been scored by IHC as DARC/ACKR1 high or low expressing. We used a panel of approximately 30 markers, including structural, immune, and other markers of interest. Following imaging, we have used cell segmentation software to quantify marker expression on a cell-by-cell basis. Using this method, we are able to conduct single-cell analyses of our markers of interest, while also retaining the spatial composition of the cells. We have used the tSNE algorithm to identify cell populations that cluster uniquely within DARC/ACKR1 high or low tumor expressing groups, specifically identifying different clusters of immune cell populations, which show different spatial expression patterns in our comparison groups. In addition to investigations of immune cell recruitment to the TME, we have also developed a novel DARC/ACKR1 breast cancer transgenic mouse model to study how disease progression may differ with differing DARC/ACKR1 phenotypes. Briefly, DARC -/- female mice were crossed with the male C3(1)Tag +/0 breast cancer transgenic mouse to generate DARC +/-, C3(1)Tag +/0 male mice. These males were subsequently backcrossed to DARC -/- females, to generate the target DARC/ACKR1 +/- or -/-, C3(1)Tag+ mice. These mice show evidence of early disease beginning at 3.5 months of age, and progress to advanced disease by 5 months of age. We have collected tumor tissue and blood specimens from mice ranging from 3.5 to 7 months of age, to characterize disease progression over time between our DARC/ACKR1 expressing and non-expressing groups. We have observed differences in tumors characteristics between our DARC/ACKR1 expressing groups, and upon histological and immunofluorescent evaluation, we have begun to observe differences in immune cell recruitment, following similar patterns to what we observed in our in silico and patient cohort analyses. Citation Format: Rachel Martini, Brittany Jenkins, Dorrah Deeb, Hiranmayi Ravichandran, Paula Ginter, Esther Cheng, Syed Hoda, Dhananjay Chitale, Haythem Ali, Eleanor Walker, Jessica Bensenhaver, Olivier Elemento, Nancy Manley, Lisa Newman, Melissa Davis. Breast tumor expression of DARC/ACKR1 and impacts on disease progression and immune cell recruitment in the tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4975.

This cohort study examines triple-negative breast cancer detection via mammography screening, treatment, and survival rates in African American and white American women.

BACKGROUND Little is known about general surgery trainees' education regarding management of breast problems. We sought to measure the impact of a dedicated breast surgery rotation on American Board of Surgery In-Service Examination (ABSITE) scores and operative volumes. METHODS A breast surgery rotation was implemented at our program in July 2016. We obtained the January 2017 ABSITE scores for postgraduate year (PGY) 1-3 residents, and obtained the case volumes for PGY 1-3 residents during the years 2015-2016 and 2016-2017. RESULTS We compared the performance on total questions and skin, soft tissue, and breast questions between the residents who had the breast rotation before the ABSITE to those that had it after. There was no difference in the average overall percentage (70.2% versus 71.7%, P = 0.55) or in the average skin, soft tissue, and breast percentage (70% versus 71.4%, P = 0.72). A postgraduate year-to-year comparison showed an increase in average total major cases among the PGY-1 residents (93.8 versus 166.8, P = 0.02), and an increase in average breast cases among the PGY-1 (17.8 versus 27 cases, P

The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa.Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression.The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019).We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

The 21-gene expression profile [Oncotype DX Recurrence Score (RS)] stratifies benefit from adjuvant chemotherapy in hormone receptor (HR)-positive, HER2/neu-negative, node-negative breast cancer. It is not routinely applied to predict neoadjuvant chemotherapy (NACT) response; data in diverse patient populations also are limited. We developed a statistical model based on standard clinicopathologic features to identify high-risk cases (RS > 30) and then evaluated ability of predicted high RS to predict for NACT downstaging. Primary surgery patients with Oncotype DX RS testing 2012–2016 were identified from a prospectively-maintained database. A RS predictive model was created and applied to a dataset of comparable NACT patients. Response was defined as tumor size decrease ≥ 1 cm. Of 394 primary surgery patients—60.4% white American; 31.0% African American—RS distribution was similar for both groups. No single feature reliably identified high RS patients; however, a model accounting for age, HR expression, proliferative index (MIB1/Ki67), histology, and tumor size was generated, with receiver operator area under the curve 0.909. Fifty-six NACT patients were identified (25 African American). Of 21 cases with all relevant clinicopathology, 14 responded to NACT and the model generated high-risk RS in 14 (100%); conversely, of 16 cases generating high-risk RS, only 2 did not respond. Predictive modelling can identify high RS patients; this model also can identify patients likely to experience primary tumor downstaging with NACT. Until this model is validated in other datasets, we recommend that Oncotype-eligible patients undergo primary surgery with decisions regarding chemotherapy made in the adjuvant setting.

Disparities in breast cancer incidence and outcome between African American and white American women are multifactorial in etiology. The increased frequency of triple-negative breast cancers (TNBC) in African American patients suggests the possible contribution of hereditary factors related to African ancestry. The University of Michigan (UM)-Komfo Anoyke Teaching Hospital (KATH) Breast Cancer Research Collaborative and International Breast Registry was established in 2004. It features epidemiologic information, tumor tissue, and germline DNA specimens from African American, white American, and Ghanaian women. This research collaborative has generated valuable findings regarding the pathogenesis and patterns of TNBC while concomitantly improving the standard of breast oncology care in Ghana. This partnership has also yielded important opportunities for academic and educational exchange. It has expanded to involve other sites in Africa and Haiti. The UM-KATH collaborative is a model for demonstrating the research and academic exchange value of international partnerships.

Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan. This research collaborative has featured educational training programs as well as scientific investigations related to the comparative biology of breast cancer in Ghanaian African, African American, and white/European American patients. Currently, the International Breast Registry has expanded to include African American patients throughout the United States by partnering with the Sisters Network (a national African American breast cancer survivors’ organization) and additional sites in Ghana (representing West Africa) as well as Ethiopia (representing East Africa). Its activities are now coordinated through the Henry Ford Health System International Center for the Study of Breast Cancer Subtypes. Herein, we review the history and results of this international program at its 10-year anniversary.

Evidence has shown that multidisciplinary specialist team evaluation and management for cancer results in better patient outcomes. For breast cancer, breast centers are where this evaluation and management occurs. The National Accreditation Program for Breast Centers has helped standardize multidisciplinary breast cancer care by defining services and standards required of accredited breast centers.

This abstract was withdrawn by the authors.

Background: The ideal timing of postmastectomy radiation therapy (PMRT) in the setting of two-stage implant-based breast reconstruction remains unclear. In this cohort study, the authors sought to determine whether complication rates differed between patients who received PMRT following tissue expander placement (TE-XRT) and those who received PMRT after exchange for permanent implants (Implant-XRT) utilizing using prospective, multicenter data. Methods: Eligible patients in the Mastectomy Reconstruction Outcomes Consortium study from 11 institutions across North America were included in the analysis. All patients had at least 6-month follow-up after their last intervention (i.e., implant exchange for TE-XRT patients, and radiation for Implant-XRT patients). Complications including seroma, hematoma, infection, wound dehiscence, capsular contracture, and implant loss were recorded. Results: The authors identified a total of 150 patients who underwent immediate, two-stage implant-based breast reconstruction and received PMRT. Of these, there were TE-XRT 104 patients (69.3 percent) and 46 (30.7 percent) Implant-XRT patients. There were no differences in the incidence of any complications or complications leading to reconstructive failure between the two cohorts. After adjusting for patient characteristics and site effect, the timing of PMRT (i.e., TE-XRT versus Implant-XRT) was not a significant predictor in the development of any complication, a major complication, or reconstructive failure. Conclusion: In the setting of PMRT and two-stage implant-based reconstruction, patients who received PMRT after expander placement (TE-XRT) did not have a higher incidence or increased odds of developing complications than those who received PMRT after exchange for a permanent implant (Implant-XRT). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Importance Compared with white American (WA) women, African American (AA) women have a 2-fold higher incidence of breast cancers that are negative for estrogen receptor, progesterone receptor, andERBB2(triple-negative breast cancer [TNBC]). Triple-negative breast cancer, compared with non-TNBC, likely arises from different pathogenetic pathways, and benign breast disease (BBD) predicts future non-TNBC. Objective To determine whether AA identity remains associated with TNBC for women with a prior diagnosis of BBD. Design, Setting, and Participants This study is a retrospective analysis of data of a cohort of 2588 AA and 3566 WA women aged between 40 and 70 years with a biopsy-proven BBD diagnosis. The data—obtained from the Pathology Information System of Henry Ford Health System (HFHS), an integrated multihospital and multispecialty health care system headquartered in Detroit, Michigan—include specimens of biopsies performed between January 1, 1994, and December 31, 2005. Data analysis was performed from November 1, 2015, to June 15, 2016. Main Outcomes and Measures Subsequent breast cancer was stratified on the basis of combinations of hormone receptor andERBB2expression. Results Case management, follow-up, and outcomes received or obtained by our cohort of 2588 AA and 3566 WA patients were similar, demonstrating that HFHS delivered care equitably. Subsequent breast cancers developed in 103 (4.1%) of AA patients (mean follow-up interval of 6.8 years) and 143 (4.0%) of WA patients (mean follow-up interval of 6.1 years). More than three-quarters of subsequent breast cancers in each subset were ductal carcinoma in situ or stage I. The 10-year probability estimate for developing TNBC was 0.56% (95% CI, 0.32%-1.0%) for AA patients and 0.25% (95% CI, 0.12%-0.53%) for WA patients. Among the 66 AA patients who developed subsequent invasive breast cancer, 16 (24.2%) developed TNBC compared with 7 (7.4%) of the 94 WA patients who developed subsequent invasive breast cancers and had complete biomarker data (P = .01). Conclusions and Relevance This study is the largest analysis to date of TNBC in the context of racial/ethnic identity and BBD as risk factors. The study found that AA identity persisted as a significant risk factor for TNBC. This finding suggests that AA identity is associated with inherent susceptibility for TNBC pathogenetic pathways.

There has been an increasing use of bilateral mastectomy (BM) for breast cancer. We sought to examine our trends among breast conservation (BCT) candidates and women recommended for unilateral mastectomy (UM). Our prospective breast cancer database was queried for women with a first-time, unilateral breast cancer. Patient and histologic factors and surgical treatment, including reconstruction, were evaluated. A detailed chart review was performed among patients from two representative time periods as to the reasons the patient underwent mastectomy. We identified 3,892 women between 2000 and 2012 of whom 60% underwent BCT, 1092 (28%) had UM and 12% underwent BM. BM rose from 4% in 2000 to a high of 19% in 2011, increasing around 2002 for women

This study uses data from Blue Cross Blue Shield of Michigan claims and enrollment files to evaluate the use of mammography among women aged 40 to 49 years, stratified by history of breast cancer.

Background: Population-based incidence rates of breast cancer (BC) that does not express the estrogen receptor (ER), progesterone receptor (PR) or overexpress the human epidermal growth factor 2 HER2/ neu (triple negative breast cancer, TNBC) are higher among Africans compared with white women. However the underlying biologic and genetic differences among different ethnicities are poorly understood and there are currently very few ethnically diverse BC models available for identifying new therapeutic options. Aim: Establish an international collaboration to: i, characterize African breast tumors ii, create models for studying these tumors and iii, identify biomarkers for early detection and treatment personalization. Methods: We have collected tumors from 154 white Americans WA, 76 African Americans, AA, 190 Ethiopians, Eth, and 286 Ghanaian (Gh) BC patients. We then established a unique resource of patient derived xenografts (PDX) from these tumors. The PDXs were then fully characterized using whole exome and RNA sequencing for the primary tumor, matched normal DNA, and corresponding low passage PDXs. Using immunohistochemistry, we evaluated the ER, PR, HER2/ neu, androgen receptor (AR), and ALDH1 (cancer stem cell marker) expression among these tumors. Based on biomarker expression the PDXs were then tested against a panel of IND drugs, either alone or in combinations, in an ex vivo organoid culture system to discover potential new therapeutic options. Results: Mean age at BC diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. The proportion of TNBC was significantly higher for the AA and Gh patients (41% and 54%, respectively) compared with the WA and Eth patients (23% and 15%, respectively); P < 0.001. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively ( P = 0.008). The Gh breast tumors exhibited the highest number of loss of function and missense mutations that are likely to impact therapy with a high frequency of P53, APC, and FGFR mutations. These mutations were maintained in the corresponding PDXs that were developed, and were thus used as biomarkers for drug screening. These tumors exhibited a gene expression signature based on the ethnicity of the patients with 2385 genes differentially expressed between Gh and AA, 1573 between AA and CA and 1317 between GH and CA. Results from our ongoing drug screening and biomarker identification will be available soon. Conclusions: Establishing the molecular and genetic platform of aggressive breast cancers occurring in women with African ancestry will help in identifying biomarkers for early cancer detection and targeted treatment stratification for optimum patient outcome. The availability of tumor models based on tumors from diverse African populations is the important missing pieces that have to be incorporated into current drug discovery efforts.

Background: Population-based incidence rates of breast cancers that are negative for the estrogen receptor (ER), progesterone receptor (PR), HER2/neu triple-negative breast cancer (TNBC) are higher among African American (AA) compared to White American (WA) women, and several studies suggest that TNBC prevalence is increased among selected populations of African patients. The colonial-era transatlantic slave trade resulted in shared ancestry between contemporary AA and Gh populations. The extent to which associations between TNBC are related to East African versus West African ancestry, and whether these associations extend to expression of additional hormone receptors such as androgen receptor (AR) and stem cell markers such as ALDH1, is uncertain, but this research may explain breast cancer disparities between domestic communities within the United States as well as between international population subsets. Methods: We utilized immunohistochemistry to evaluate ER, PR, HER2/neu, AR and ALDH1 expression among White American (n=153), African American (n=76), Ethiopian (Eth)/East African (n=90), and Ghanaian (Gh)/West African (n=286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. Frequency of TNBC was significantly higher for the AA and Gh patients (41% and 54%, respectively) compared to the WA and Eth patients (23% and 15%, respectively; p Conclusions: Extent of African ancestry appears to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1. Citation Format: Evelyn M. Jiagge, Aisha Jibri, Jessica Bensenhaver, Max Wicha, Baffour Awuah, Sofia Merajver, Lisa Newman. Androgen receptor and ALDH1 expression among internationally diverse patient populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1639.

e13114Background: 80% of breast cancers - BC are basal; aggressive, and negative for ER, PR and HER2 over expression, termed triple negative - TNBC. In the US, the incidence rate of TNBC is two-fol...

Ductal carcinoma in situ and microinvasive/borderline breast cancer / , Ductal carcinoma in situ and microinvasive/borderline breast cancer / , کتابخانه دیجیتال جندی شاپور اهواز

Screening mammography programs have resulted in dramatic increases in the volume of ductal carcinoma in situ (DCIS) cases diagnosed in the USA over the past 40 years. This has prompted a reevaluation of the historic approach to routine management of DCIS via mastectomy. Prospective, randomized clinical trials have now documented the safety of breast-conserving surgery for DCIS and have also revealed benefits of adjuvant endocrine therapy for these lesions, as most are hormone receptor positive, and the local, antiproliferative activity of these agents suppresses risk of local recurrence in lumpectomy cases. Adjuvant radiation has been widely shown to be beneficial as an adjunct to lumpectomy, but whether radiation and endocrine therapy are interchangeable versus additive in reducing risk of local recurrence remains open to further study. Whether aromatase inhibitors will prove to be of greater benefit than tamoxifen is a subject of ongoing clinical trials.

Efficacy of breastconserving surgery plus radiation therapy versus breastconserving surgery alone to reduce risk of local recurrence of DCIS was established by high caliber prospective randomized trials; however, no survival benefit was seen. For this reason, some argue that radiation therapy is overtreatment for certain DCIS cases and that it is appropriate for select subgroups to be treated with breast-conserving surgery alone. There have been promising results from retrospective studies aimed at identifying such low-risk DCIS subgroups, but reproducing these findings in prospective randomized trials has been difficult. Today, after a thorough provider–patient discussion of risk, there are some cases for which consideration of conserving surgery alone is reasonable; however, as it has well-established evidence-based benefit, conserving surgery plus radiation therapy is still recommended for most cases.

TNBC is the only subtype of breast cancer for which there are no approved targeted therapies. In the US, its incidence is highest in women with African ancestry (AA); in western sub-Saharan Africa, single-institution studies show that TNBC constitutes 40- 80% of all breast cancers. Given the Caucasian/AA survival disparity in breast cancer, there is an urgent need to find actionable targets in TNBC of all ethnicities, but especially in TNBC in AA, which are suspected to be more aggressive. Breast cancer stem cells, the small population of cells that have been shown to mediate breast tumor initiation, metastasis, and resistance to conventional therapy have also been reported to mediate the heterogeneity of TNBC and are especially abundant in TNBC in AA women. Here, we sought to better understand the biology of TNBC by finding genes and pathways that are differentially expressed in the stem cell population of patient derived xenografts (PDX) from TNBC from Ghanaian (G), AA and Caucasian (C) women and the effect of these differentially expressed genes on the stem cell phenotype in these primary tumors. We isolated the ALDH+ and the CD44+/CD24- stem cell populations from the bulk cells from 15 PDXs using flow cytometry. We performed RNA sequencing (Illumina HiSeq platform) on the isolated populations and bulk cells (45). Comprehensive bioinformatics analyses led to the identificationof highly significantly differentially expressed genes and pathways between the cell populations. By principal component analysis, the tumors were very heterogeneous. However, the ALDH+ cells separated out from the CD44+/CD24- and the bulk cells. We identified 14 genes that were simultaneously differentially expressed between the ALDH+ vs the CD44+/CD24- as well as ALDH+ VS bulk (p-value Citation Format: Evelyn M. Jiagge, Shukmei Wong, Rabia Gilani, Sean Mcdermott, Lisa Newman, Jessica Bensenhaver, Max Wicha, John Carpten, Sofia Merajver. Aldh expressing stem cells mediate tumor initiation and metastasis in triple negative breast cancers across different ethnicities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3371. doi:10.1158/1538-7445.AM2017-3371

1101 Background: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2/ neu(triple negative breast cancer {TNBC}) are higher among African American (AA) compared to White American (WA) women. Several studies show higher TNBC frequency among selected populations of African patients. The colonial-era trans-Atlantic slave trade resulted in shared West African ancestry between contemporary AA and Ghanaian (Gh) populations. The extent to which TNBC susceptibility is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers such as Androgen Receptor (AR) and mammary stem cell marker ALDH1 is unknown. Methods: We used immunohistochemistry to assess ER, PR, HER2/ neu, AR and ALDH1 among WA (n = 153); AA (n = 76); Ethiopian (Eth)/East African (n = 90) and (Gh)/West African (n = 286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. Frequency of TNBC was significantly higher for AA and Gh patients (54% and 41%, respectively) compared to WA and Eth patients (23% and 15%, respectively); p < 0.001. These associations were unchanged when limited to patients age 50 and younger (47% and 49% for AA and Gh, respectively; versus 18% and 16% for WA and Eth, respectively); p < 0.001. Frequency of ALDH1 positivity was also higher for tumors from AA and Gh patients (32% and 36%, respectively) compared to those from WA and Eth patients (23% and 17%, respectively); p = 0.007. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively (p = 0.008). Conclusions: We found a correlation between extent of African ancestry and risk of particular BC phenotypes. West African ancestry was associated with increased risk of TNBC and breast cancers that are positive for ALDH1. Future studies of hereditary TNBC susceptibility among women with African ancestry are warranted.

Evidence has shown that multidisciplinary specialist team evaluation and management for cancer results in better patient outcomes. For breast cancer, breast centers are where this evaluation and management occurs. The National Accreditation Program for Breast Centers has helped standardize multidisciplinary breast cancer care by defining services and standards required of accredited breast centers.

264 Background: The purpose of this study was to investigate clinical and non-clinical factors associated with time to initiation of breast cancer adjuvant chemotherapy following the final definitive surgery in a state-wide collaborative. Methods: We collected prospective data from all patients who received adjuvant chemotherapy for Stages I - III breast cancer in 25 health systems in the Michigan Breast Oncology Quality Initiative (MiBOQI) between 2006 - 2014. MiBOQI is a Blue Cross Blue Shield of Michigan/Blue Care Network-sponsored quality collaborative. The dependent variable was time to initiation of adjuvant chemotherapy. Time to chemotherapy was examined according to clinical and non-clinical patient and treatment factors and by health system, both with and without adjustment for patient and treatment variables. Results: Complete data were available for 7,513 of 8,236 eligible (91%) patients. The mean time to chemotherapy was 43 days (range 5-390). In multivariate analyses, clinical factors independently associated with longer time to chemotherapy included increasing age, greater comorbidity, and obesity (p value < 0.0001 for all). Higher stage disease was associated with shorter time to chemotherapy (p < 0.0001); there was no association with hormone receptor or HER2 status. Treatment factors associated with longer time to chemotherapy were breast reconstruction, receipt of genomic assays, and receipt of advanced imaging (p value < 0.0001 for all). Non-clinical factors—minority status, higher area-level poverty, and non-private insurance—were also independently associated with longer time to chemotherapy (p value < 0.0001 for all). In addition, time to chemotherapy varied significantly between health system (p < 0.0001); this difference persisted after adjustment for all patient and treatment factors. Conclusions: Clinical and non-clinical factors, including site of care, are associated with variation in time to initiation of chemotherapy. Identifying patient-level factors and processes of care that facilitate or impede timely initiation of chemotherapy may decrease unwarranted variation in care delivery across a collaborative network.

Background Carotid artery stenting (CAS) has been advocated as an alternative to carotid endarterectomy (CEA) in high-risk surgical patients, including stenosis after CEA. This study compared early and midterm clinical outcomes for primary CAS vs CAS for post-CEA stenosis. Methods This study analyzed 180 high-risk surgical patients: 68 had primary CAS (group A), and 112 had CAS for post-CEA stenosis (group B). Patients were followed-up prospectively and had duplex ultrasound imaging at 1 month and every 6 months thereafter. All patients had cerebral protection devices. Kaplan-Meier life-table analysis was used to estimate rates of freedom from stroke, stroke-free survival, ≥50% in-stent stenosis, ≥80% in-stent stenosis, and target vessel reintervention (TVR). Results Patients had comparable demographic and clinical characteristics. Carotid stent locations were similar. Indications for CAS were transient ischemic attacks (TIA) or stroke in 50% for group A and 45% for group B. The mean follow-up was comparable, at 21 (range, 1-73) vs 25 (range, 1-78) months, respectively. The technical success rate was 100%. The perioperative stroke rates and combined stroke/death/myocardial infarction (MI) rates were 7.4% for group A vs 0.9% for group B ( P = .0294). No perioperative MIs occurred in either group. One death was secondary to stroke. The combined early and late stroke rates were 10.8% for group A and 1.8% for group B ( P = .0275). The stroke-free rates at 1, 2, 3, and 4 years for groups A and B were 89%, 89%, 89%, and 89%; and 98%, 98%, 98%, and 98%, respectively ( P = .0105). The rates of freedom from ≥50% carotid in-stent stenosis were 94%, 83%, 83%, and 66% for group A vs 96%, 91%, 83%, and 72% for group B ( P = .4705). Two patients (3%) in group A and seven patients (6.3%) in group B had ≥80% in-stent stenosis (all were asymptomatic except one). The freedom from ≥80% in-stent stenosis at 1, 2, 3, and 4 years for groups A and B were 100%, 98%, 98%, and 78% vs 99%, 96%, 92%, and 87%, respectively ( P = .7005). Freedom from TVR rates at 1, 2, 3, and 4 years for groups A and B were 100%, 100%, 100%, and 100% vs 99%, 97%, 97%, and 92%, respectively ( P = .261). Conclusions CAS for post-CEA stenosis carried a lower risk of early postprocedural neurologic events than primary CAS, with a trend toward a higher restenosis rate during follow-up.

In the US where extensive studies have been conducted, African-American(AA) women have poorer survival from breast cancer (BC) even after adjusting for stage, age, treatment and co-morbid conditions. Since survival in BC is mainly dependent on the appearance and robustness of metastasis, we have hypothesized that BC occurring in women with African ancestry have a greater metastatic potential. With the growing evidence that BC tumor initiation, metastases and recurrence is driven by stem-like cancer cells, we further hypothesize that BC in women of African descent has aggressive phenotypic characteristics that result from the integration of signaling alterations and metabolic adaptations in their cancer stem cells. Rodent xenograft models are powerful tools for studying tumor biology and treatment response to novel agents, but they are challenging to develop in the laboratory. Here we describe the first-ever creation of a library of xenografts from a series of patients affected with triple negative breast cancer (TNBC) from sub-Saharan Africa, based upon a unique international collaboration; we also report on studies that are being conducted on the xenografts to understand the stem cell biology of aggressive African breast cancers. Methods: Our research team explored several different strategies for obtaining fresh tumor specimens from Ghanaian patients with aggressive TNBC tumors, undergoing surgery in Kumasi, Ghana, and rapidly transporting these tissues for implantation into immunocompromised mice in the United States. Xenograft tumors were also developed from AA and Caucasian American (CA) patients undergoing surgery in the United States. The whole genome expression patterns of the bulk tumor as well as the stem cell compartments were compared for AA, Ghanaian and CA TNBC. Single cells from the tumors were grown in suspension and in attachment plates. Results: Successful xenografts were created by harvesting fresh tissue from patients undergoing surgery in Ghana, slow freezing tumor pieces at -80o C and transporting it on dry ice by air to the United States within 24-36 hours to implant into nod scid gamma mice. Currently we have successful growth, as follows: 12 tumors from 4 patients growing in 10 mice. We have successful growth of tumorspheres and cell lines from single cells separated from the xenografts, as additional resources for biological studies of signaling and metastases. In a preliminary study, we have performed a gene array expression study of AA and White American triple negative and estrogen positive cell lines that show significantly different gene expression patterns, with the cell lines of high African ancestry segregating from Caucasian cell lines . Conclusions: The study of aggressive breast cancers in African populations is feasible through the creation of xenografts from fresh tumor tissue harvested from the treating facilities and transported to laboratories in the United States. International collaborations are critical for this process and should thus be encouraged, to create the appropriate resources worldwide to improve our understanding of aggressive BC subtypes.. Moreover, we are finding common expression patterns in TNBC of African extraction. This will help advance our understanding of the survival disparities. To this end, we will be able to test the observed differences in the new tumorspheres and cell lines developed directly from patients. Citation Format: Evelyn M. Jiagge, Jessica Bensenhaver, Sean McDermott, Awuah Baffour, Max Wicha, Lisa A. Newman, Sofia Merajver. Differences in breast cancer stem cell signaling and metabolic integration associated with African versus European ancestry. [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 PL03-03. doi:10.1158/1538-7755.DISP13-PL03-03

Background The optimal duplex ultrasound (DUS) velocity criteria to determine in-stent carotid restenosis are controversial. We previously reported the optimal DUS velocities for ≥30% in-stent restenosis. This prospective study will further define the optimal velocities in detecting various severities of in-stent restenosis: ≥30%, ≥50%, and 80% to 99%. Methods The analysis included 144 patients who underwent carotid artery stenting as a part of clinical trials. All patients had completion arteriograms and underwent postoperative carotid DUS imaging, which was repeated at 1 month and every 6 months thereafter. Patients with peak systolic velocities (PSVs) of the internal carotid artery (ICA) of ≥130 cm/s underwent carotid computed tomography (CT)/angiogram. The PSVs and end-diastolic velocities of the ICA and common carotid artery (CCA) and the PSV of the ICA/CCA ratios were recorded. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal velocity criteria for the diagnosis of ≥30, ≥50, and ≥80% restenosis. Results The mean follow-up was 20 months (range, 1-78 months). Available for analysis were 215 pairs of imaging (DUS vs CTA/angiography) studies. The accuracy of CTA vs carotid arteriogram was confirmed in a subset of 22 patients (κ = 0.81). The ROC analysis demonstrated that an ICA PSV of ≥154 cm/s was optimal for ≥30% stenosis with a sensitivity of 99%, specificity of 89%, positive-predictive value (PPV) of 96%, negative-predictive value (NPV) of 97%, and overall accuracy (OA) of 96%. An ICA EDV of 42 cm/s had sensitivity, specificity, PPV, NPV, and OA in detecting ≥30% stenosis of 86%, 62%, 87%, 60%, and 80%, respectively. An ICA PSV of ≥224 cm/s was optimal for >50% stenosis with a sensitivity of 99%, specificity of 90%, PPV of 99%, NPV of 90%, and OA of 98%. An ICA EDV of 88 cm/s had sensitivity, specificity, PPV, NPV, and OA in detecting ≥50% stenosis of 96%, 100%, 100%, 100%, 53%, and 96%. An ICA/CCA ratio of 3.439 had sensitivity, specificity, PPV, NPV, and OA in detecting ≥50% stenosis of 96%, 100%, 100%, 100%, 58%, and 96%, respectively. An ICA PSV of ≥325 cm/s was optimal for >80% stenosis with a sensitivity of 100%, specificity of 99%, PPV of 100%, NPV of 88%, and OA of 99%. An ICA EDV of 119 cm/sec had sensitivity, specificity, PPV, NPV, and OA in detecting ≥80% stenosis of 99%, 100%, 100%, 100%, 75%, and 99%, respectively. The PSV of the stented artery was a better predictor for in-stent restenosis than the end-diastolic velocity or ICA/CCA ratio. Conclusion The optimal DUS velocity criteria for in-stent restenosis of ≥30%, ≥50%, and ≥80% were the PSVs of 154, 224, and 325 cm/s, respectively.