Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. METHODS: This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. RESULTS: Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. CONCLUSION: This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

Postneoadjuvant Pure and Predominantly Pure Intralymphatic Breast Carcinoma: Case Series and Literature Review.

Locally advanced breast cancer is typically treated with neoadjuvant chemotherapy to decrease tumor size and optimize surgical results. Cases of pathologic complete response, are associated with favorable long-term outcomes. The American Joint Committee on Cancer (AJCC) defines pathologic complete response as a lack of residual invasive disease in the breast or lymph nodes or only residual ductal carcinoma in situ. Three studies have examined the unique pattern of postneoadjuvant pure or predominantly pure intralymphatic carcinoma. These studies are small and the prognosis associated with this disease pattern is still unclear. The current study aims to describe clinicopathologic findings associated with pure and predominantly pure intralymphatic carcinoma postneoadjuvant chemotherapy. Electronic medical records were searched to identify patients treated with postneoadjuvant mastectomy between 2010 and 2017. Cases were included if they met the previously defined definitions for pure or predominantly pure intralymphatic carcinoma. Of 479 postneoadjuvant mastectomies, 5 patients had pure intralymphatic carcinoma and 6 patients had predominantly pure. Overall, 50% (3/6) of patients with predominantly pure pattern died of metastatic disease within 14 months of mastectomy, whereas 1 patient with pure intralymphatic carcinoma (ypN0) died of metastatic disease 25 months postmastectomy, revealing a better prognosis associated with pure intralymphatic carcinoma when compared with predominantly pure. The diligent gross examination is required to identify patients with both patterns of residual disease. A standardized approach to incorporating lymphovascular invasion into postneoadjuvant staging may be useful from both a clinical and research perspective. The published case numbers remain small and understanding the true clinical significance still depends on additional studies.

Aortic dissection and accelerated aneurysmal degeneration in a patient with giant cell arteritis.

Giant cell arteritis (GCA) is associated with nonatheromatous aortic pathology. Here we present a case in which a 76-year-old woman with a biopsy-proven history of GCA and a previous repair of her ascending aortic aneurysm presents with an acute dissection of a 4-cm aneurysm in the descending thoracic aorta. It was treated using endovascular techniques. This report adds to a growing body of evidence that GCA is a risk factor for aortic dissection and nonatheromatous aortic aneurysms.

Benign breast papillary lesions diagnosed on core biopsy: upgrade rate and risk factors associated with malignancy on surgical excision.

Evaluation of radiologically detected breast lesions is a common task in surgical pathology. Some benign lesions on biopsy are associated with an upgrade to in situ or invasive carcinoma on excision. The non-atypical breast papilloma has published upgrade rates of 0 to 29%. Traditionally, papillomas have been managed surgically, but the wide range of upgrade rates has raised uncertainty about the need for routine surgical excision. This study aims to identify risk factors associated with upgrade and determine the upgrade rate of non-atypical papillomas at our institution. In a retrospective review of pathology reports, we identified 266 patients with a diagnosis of benign papilloma on breast core biopsy. One hundred eighty-two patients underwent surgical resection. The final surgical pathology reports of all patients were reviewed and divided into one of two groups-benign or malignant. Twenty-one patients had a final diagnosis of in situ or invasive carcinoma, resulting in an upgrade rate of 12%. Radiologically detected lesions with calcifications were at higher risk for upgrade (OR = 4.45, 95% CI 1.08-18.27) than lesions without calcifications. Additionally, advanced patient age (OR = 1.07, 95% CI 1.03-1.13) and lesion size greater than 0.5 cm (OR = 2.59, 95% CI 0.38-17.48) was associated with upgrade to malignancy. Routine surgical excision of all papillomas is not recommended. Younger patients without high-risk features may benefit from clinical and radiologic follow-up alone. Accurate risk stratification will spare low-risk women unnecessary surgery.

Coronary artery Doppler patterns are associated with clinical outcomes post-arterial switch operation for transposition of the great arteries.

Aims: Transposition of the great arteries (TGA) is generally repaired using the arterial switch operation (ASO) involving coronary transfer. The objective of this prospective study was to determine whether specific coronary Doppler patterns intra-operatively predicted adverse early myocardial events. Methods and results: Patients < 3 months old with TGA undergoing the ASO were eligible. All patients (when feasible) underwent an intra-operative transoesophageal echo (TEE) plus an epicardial echo and had pre-op, early post-op, pre-discharge and follow-up functional echocardiograms. The primary endpoint was a composite myocardial ischaemic event (any of: post-operative ST changes, ventricular tachycardia, need for extracorporeal membrane oxygenation (ECMO). Associations of coronary Doppler flow patterns with outcomes were modelled with logistic regression models. From May 2009 to December 2012, 40 patients (29 male, birth weight 3.29 ± 0.58 kg) were recruited. n = 32 had TEE + epicardial, four TEE only, four epicardial only. Seven (18%) patients had an adverse myocardial event (five ST changes, two ventricular tachycardia (one also ECMO). There was one death. n = 3 had a coronary artery (CA) revision post-operatively, and three had re-operation for non-CA causes. By TEE, flow reversal in the left coronary artery was associated with the composite endpoint [Odds Ratio (OR) 31.5, P = 0.004], and for chest open > 3 days (OR 6.67, P = 0.0537). Coronary Doppler flow patterns were similar by TEE and epicardial echo. The tissue Doppler parameters showed an early post-op decrease (P < 0.001 for all measures), with full recovery at follow-up in 31/37 cases. Conclusion: Intra-operative evaluation of coronary artery flow patterns should be considered for patients undergoing the ASO.

Factors associated with in utero demise of fetuses that have underlying cardiac pathologies.

Factors associated with in utero fetal demise (IUFD) of fetuses that have underlying cardiac pathologies are largely unknown. This case-control study aimed to define the prevalence of IUFD in fetuses with a diagnosis of cardiac pathologies and to identify prenatal predictors of IUFD. Between January 2004 and December 2010, 74 IUFD cases [4.6 %; 95 % confidence interval (CI) 3.7-5.8 %] were identified from 1,584 cases with a diagnosis of structural or functional cardiac lesions in the Hospital for Sick Children database. The cases were divided into right-sided (N = 28), left-sided (N = 23), great artery (N = 8), and miscellaneous (N = 15) groups. The control subjects (1:1 ratio) were fetuses that had cardiac pathology diagnosed within 48 h of the IUFD case. Multivariable regression models were used to determine echocardiographic predictors of IUFD. The prevalence of IUFD was greatest in hypertrophic cardiomyopathy (8/16, 50 %) and Ebstein's anomaly/tricuspid dysplasia (4/15, 27 %) and lowest in transposition of the great arteries (2/85, 1 %). The findings showed IUFD to be associated with hydrops in 17 (23 %) of the 74 cases and arrhythmia in 11 (15 %) of the 74 cases. The factors identified by univariable logistic regression analyses were right ventricular dysfunction [odds ratio (OR) 2.7; p = 0.001], left ventricular dysfunction (OR 1.8; p = 0.007), umbilical vein pulsations (OR 10.9; p = 0.002), and abnormal ductus venosus flow (OR 3.3; p = 0.01). The factors associated with IUFD in multivariable logistic regression models were cardiomegaly (OR 5.6; p = 0.01), hydrops (OR 29.5; p = 0.001), pericardial effusion (OR 4.1; p = 0.06), and extracardiac abnormalities (OR 7.2; p < 0.001). The prevalence of IUFD is greatest in conditions affecting the ventricular myocardium. The onset of IUFD appears to be related initially to right ventricular dysfunction. Closer surveillance is recommended for lesions at risk of IUFD.