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Triple-negative breast cancers (TNBCs) are more common among African-ancestry populations, such as African Americans and western, sub-Saharan Africans, compared with European-ancestry populations. This phenotype prevalence contributes to disparities in breast cancer outcomes between African Americans and White Americans. Breast cancer stem cells represent the tumor subpopulation involved in metastatic virulence, and ongoing research seeks to characterize the extent to which TNBC versus non-TNBC stem cells may differ. This review summarizes the existing literature regarding TNBCs and stem cells as they pertain to the burden of breast cancer among African-ancestry populations. Additional research related to variations in somatic tumor genomics between the African-American and White-American populations is also summarized. This review furthermore explores the history of insights regarding breast cancer disparities related to racial/ethnic identity, socioeconomic status, and tumor biology., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Accurate and timely molecular test results play an important role in patient management; consequently, there is a customer expectation of short testing turnaround times. Baseline data analysis revealed that the greatest challenge to timely result generation occurred in the preanalytic phase of specimen collection and transport. Here, we describe our efforts to improve molecular testing turnaround times by focusing primarily on redesign of preanalytic processes using the principles of LEAN production. Our goal was to complete greater than 90% of the molecular tests in less than 3 days. The project required cooperation from different laboratory disciplines as well as individuals outside of the laboratory. The redesigned processes involved defining and standardizing the protocols and approaching blood and tissue specimens as analytes for molecular testing. The LEAN process resulted in fewer steps, approaching the ideal of a one-piece flow for specimens through collection/retrieval, transport, and different aspects of the testing process. The outcome of introducing the LEAN process has been a 44% reduction in molecular test turnaround time for tissue specimens, from an average of 2.7 to 1.5 days. In addition, extending LEAN work principles to the clinician suppliers has resulted in a markedly increased number of properly collected and shipped blood specimens (from 50 to 87%). These continuous quality improvements were accomplished by empowered workers in a blame-free environment and are now being sustained with minimal management involvement.

Lung adenocarcinomas responsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors possess EGFR mutations and often increased EGFR copy number. We prospectively studied 334 clinical cases using polymerase chain reaction-based assays to detect deletions within exon 19 and the L858R mutation in exon 21, which together account for approximately 90% of EGFR mutations. Seventy-eight (23%) of these tumors had an EGFR mutation, with 55 (71%) exon 19 deletions and 23 (29%) exon 21 L858R mutations. We were able to compare mutant and normal EGFR alleles and found a preferential amplification of the mutant allele. The association of mutations with EGFR amplification (determined by chromogenic in situ hybridization) and EGFR expression (determined by immunohistochemistry) was further examined in a subset of 60 tumors. EGFR amplification (> or =5 EGFR signals per nucleus) was seen in 15 of 29 (52%) EGFR-mutated tumors but in only five of 31 (6%) non-mutated tumors (P = 0.006). EGFR overexpression was strongly associated with amplification but was statistically independent of EGFR mutation. Most patients with EGFR mutations (17 of 29, 59%) never smoked compared with 13% (four of 31) of patients lacking such mutations (P = 0.0003). The association of amplification with smoking status was marginal and was nonexistent with EGFR expression. Thus, these results indicate that EGFR amplification, preferentially of the mutant allele, often accompanies EGFR mutation, whereas EGFR immunohistochemical staining associates with amplification but cannot predict EGFR mutation status.

Background: Somatic mutations in EGFR (exons 19 and 21) and KRAS (exon 2) are found in lung adenocarcinomas and have potential prognostic value in patients with advanced disease. These mutations also have therapeutic significance, as they predict for sensitivity and resistance, respectively, to EGFR tyrosine kinase inhibitor therapy. Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established., Methods: We analyzed the clinical characteristics and outcomes data for 296 patients who underwent resection at our institution for stage I-III lung adenocarcinoma. Tumors were assessed for both EGFR and KRAS mutations by established methods., Results: EGFR and KRAS mutations were found in tumors from 40 (14%) and 50 (17%) patients, respectively. Patients with EGFR mutant tumors were more likely to be never smokers (48%), present with stage I disease (88%), and had a 90% (95% confidence interval [CI] 70-97%) 3-year overall survival, whereas patients with KRAS mutant tumors were more likely to be former/current smokers (92%), present with locally advanced disease (40%), and had a 66% (95% CI 48-79%) 3-year overall survival., Conclusions: EGFR and KRAS mutations define distinct molecular subsets of resected lung adenocarcinoma. Because EGFR and KRAS mutations also predict whether tumors are sensitive or resistant, respectively, to EGFR tyrosine kinase inhibitors, they can readily be used in clinical trials to help guide the administration of specific types of adjuvant therapy.