Survival Outcomes in Women with Unilateral, Triple-Negative, Breast Cancer Correlated with Contralateral Prophylactic Mastectomy.

BACKGROUND: Despite increased utilization of contralateral prophylactic mastectomy (CPM), there is insufficient evidence that it improves survival in average-risk women with unilateral breast cancer. CPM may be of heightened interest to patients with triple negative breast cancer (TNBC) because these patients are more likely to have BRCA1 mutation-associated disease and are not candidates for the chemoprevention benefits of adjuvant endocrine therapy. METHODS: Survival and recurrence outcomes were evaluated for all TNBC patients from a multi-institutional database (1999-2018) at two academic cancer programs in two metropolitan cities of the Northeast and Midwest. Median follow-up time was 3.7 years. RESULTS: Seven hundred and nighty six TNBC patients were evaluated and 15.45% underwent CPM. Women undergoing CPM were more likely to be white (p < 0.001), younger (p < 0.001), and underwent genetic testing (p < 0.001). A borderline survival benefit was observed for TNBC patients undergoing CPM (5-year overall survival 95.1% vs. 85.0%; p = 0.05). There was no difference in survival when BRCA mutation carriers were excluded (5-year overall survival 94.1% vs. 85.2%; p = 0.12). For BRCA mutation carriers, a numeric trend was observed for improved survival for patients undergoing CPM (5-year overall survival 97.2% vs. 84.1%; p = 0.35). Among patients not undergoing CPM, the rate of developing a new primary breast cancer was 2.2% (15/673). Among these 15 patients, 20% (3/15) were known BRCA mutation carriers. CONCLUSIONS: Our data demonstrate no survival benefit for TNBC patients without BRCA1/2 mutations undergoing CPM.

Benefit of adjuvant chemotherapy in node-negative T1a versus T1b and T1c triple-negative breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. METHODS: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. RESULTS: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. CONCLUSIONS: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.

Outcome of African-American compared to White-American patients with early-stage breast cancer, stratified by phenotype.

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 < 0.0001). AA women also had higher incidence of HER2 positive cancers (AA 16.8% vs. WA 15.3%; p < 0.0001). WA women had a significantly higher distribution of Non-TNBC/HER2-negative phenotype (AA 55% vs. WA 65%; p < 0.0001). Furthermore, a subgroup analysis was done for a sentinel lymph node (SLN) negative cohort that showed higher rates of grade 3 tumors in AA (AA 35% vs. WA 23%; p < 0.0001); and higher rates of grade 1 and grade 2 tumors in WA (30% vs. 21% and 44% vs. 40%). Despite higher grade tumors in AA women, five-year overall survival outcomes in SLN-negative cohort did not differ between AA and WA women when stratifying based on tumor subtype. CONCLUSION: Breast cancer survival disparities in AA and WA women with SLN-negative breast cancer are diminished when evaluated at early-stage cancers defined by SLN-negative tumors. Our evaluation suggests that when diagnosed early, phenotype does not contribute to racial survival outcomes. The lower survival rate in AA women with breast cancer may be attributed to later stage biology between the two races, or underlying socioeconomic disparities.

A rare presentation of bilateral, synchronous male breast cancer.

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.

Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative.

OBJECTIVE: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations. BACKGROUND: 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. METHODS: 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. RESULTS: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). 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 (P < 0.0001), quantified West African Ancestry (P < 0.0001) 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. CONCLUSIONS: 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.

Effects of Implementing a Breast Surgery Rotation on ABSITE Scores and Surgical Case Volume.

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 < 0.01) and PGY-2 (27.3 versus 47.7 cases, P = 0.02) years. There was an increase in the proportion of complex breast cases performed by PGY-3 residents (23.2% versus 33.1%, P = 0.01). CONCLUSIONS: A dedicated breast surgery rotation did not detract from the nonbreast general surgery educational experience of junior residents (as measured by ABSITE scores), and it increased the case volume of breast as well as total major cases among junior residents. A breast surgery rotation is valuable for strengthening surgical case volumes.

Distribution and Short-term Prognostic Value of the 21-gene recurrence score in African American compared to White American breast cancer patients.

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.

Utilization of the 21-Gene Recurrence Score in a Diverse Breast Cancer Patient Population: Development of a Clinicopathologic Model to Predict High-Risk Scores and Response to Neoadjuvant Chemotherapy.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). CONCLUSIONS: This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

Differences between Breast Conservation-Eligible Patients and Unilateral Mastectomy Patients in Choosing Contralateral Prophylactic Mastectomies.

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 <40. BCT was less likely with decreasing age (p < 0.0001), lobular histology (p < 0.0001), higher stage (p < 0.0001) and decreasing BMI (p < 0.0001). Among mastectomy patients, contralateral mastectomy was associated with decreasing age (p < 0.0001), Caucasian race (p < 0.0001), and lower stage (p = 0.005). Over time, indications for mastectomy decreased while patients deemed BCT-eligible opting for UM or BM increased dramatically. Increases in the use of BM are in large part among women who were otherwise BCT-eligible. Factors associated with BM use are different for BCT-eligible patients and those recommended for UM. A better understanding of the factors driving individual patient choices is needed.

Global surgical oncology disease burden: addressing disparities via global surgery initiatives: the University of Michigan International Breast Cancer Registry.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The UM-KATH collaborative is a model for demonstrating the research and academic exchange value of international partnerships.

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 %; p < 0.0001), 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). CONCLUSION: 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.

Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.

BACKGROUND: Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies. METHODS: Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed. RESULTS: For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L. CONCLUSIONS: Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Screening mammography mitigates breast cancer disparities through early detection of triple negative breast cancer.

PURPOSE: Screening mammography improves breast cancer survival through early detection, but Triple Negative Breast Cancer (TNBC) is more difficult to detect on mammography and has lower survival compared to non-TNBC, even when detected at early stages. TNBC is twice as common among African American (AA) compared to White American (WA) women, thereby contributing to the 40% higher breast cancer mortality rates observed in AA women. The role of screening mammography in addressing breast cancer disparities is therefore worthy of study. METHODS: Outcomes were evaluated for TNBC patients treated in the prospectively-maintained databases of academic cancer programs in two metropolitan cities of the Northeast and Midwest, 1998-2018. RESULTS: Of 756 TNBC cases, 301 (39.8%) were mammographically screen-detected. 46% of 189 AA and 38.5% of 460 WA patients had screen-detected TNBC (p = 0.16). 25.3% of 257 TNBC cases ≤50 years old had screen-detected disease compared to 47.3% of 499 TNBC cases >50 years old (p < 0.0001). 220/301 (73.1%) screen-detected TNBC cases were T1 lesions versus 118/359 (32.9%) non-screen-detected cases (p < 0.0001). Screen-detected TNBC was more likely to be node-negative (51.9% v. 40.4%; p < 0.0001). Five-year overall survival was better in screen-detected TNBC compared to nonscreen-detected TNBC (92.8% v. 81.5%; p < 0.0001) in the entire cohort. The magnitude of this effect was most significant among AA patients (Fig. 1). Screening-related survival patterns were similar among AA and WA patients in both cities. CONCLUSION: Data from two different cities demonstrates the value of screening mammography to mitigate breast cancer disparities in AA women through the early detection of TNBC.

Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.

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.

Primary carotid artery stenting versus carotid artery stenting for postcarotid endarterectomy stenosis.

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, > or =50% in-stent stenosis, > or =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 > or =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 > or =80% in-stent stenosis (all were asymptomatic except one). The freedom from > or =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.

Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer.

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.