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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.

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.

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.

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

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.

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.

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 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.