ABSTRACT
PURPOSE: We compared the mutational profile of second breast cancers (SBC) following first ipislateral hormone receptor-positive breast cancers of patient-matched tumors to distinguish new primaries from true recurrences. EXPERIMENTAL DESIGN: Targeted next-generation sequencing using the Oncomine Tumor Mutation Load Assay. Variants were filtered according to their allele frequency ≥ 5%, read count ≥ 5X, and genomic effect and annotation. Whole genome comparative genomic hybridization array (CGH) was also performed to evaluate clonality. RESULTS: Among the 131 eligible patients, 96 paired first breast cancer (FBC) and SBC were successfully sequenced and analyzed. Unshared variants specific to the FBC and SBC were identified in 71.9% and 61.5%, respectively. Paired samples exhibited similar frequency of gene variants, median number of variants per sample, and variant allele frequency of the reported variants except for GATA3. Among the 30 most frequent gene alterations, ARIDIA, NSD2, and SETD2 had statistically significant discordance rates in paired samples. Seventeen paired samples (17.7%) exhibited common variants and were considered true recurrences; these patients had a trend for less favorable survival outcomes. Among the 8 patients with available tissue for CGH analysis and considered new primaries by comparison of the mutation profiles, 4 patients had clonally related tumors. CONCLUSIONS: Patient-matched FBC and SBC analysis revealed that only a minority of patients exhibited common gene variants between the first and second tumor. Further analysis using larger cohorts, preferably using single-cell analyses to account for clonality, might better select patients with true recurrences and thereby better inform the decision-making process.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Comparative Genomic Hybridization , Mutation , Genomics , RecurrenceABSTRACT
INTRODUCTION: Oncotype DX is approved in multiple countries but its cost-effectiveness is a matter of considerable health debate. Lebanon is high-middle income country according to the World Bank classification however it is facing a mounting financial and health care burden from cancer. Therefore, we conducted a costeffectiveness analysis of Oncotype DX based Lebanese on real-life data. METHODS: We updated a Canadian cost-effectiveness model of Oncotype DX by incorporating Lebanese data. The patient population was a real-life cohort of 82 women diagnosed with hormone receptor - positive and HER2 - negative early breast cancer. RESULTS: Overall, providing Oncotype DX to only intermediate Adjuvant! Online risk patients costs an additional $83 CAD (93,883 LBP) per additional QALY. From this point, extending provision to also cover high Adjuvant! Online risk patients costs an additional $736 CAD (831,578 LBP) per additional QALY. From this point, extending provision further to also cover low Adjuvant! Online risk patients (such that Oncotype DX is provided to all patients) costs an additional $14,562 CAD (16.46m LBP) per additional QALY. Given that most women in our population-based sample were classified as intermediate Adjuvant! Online risk patients, our study focused on this subset in the second analysis. Providing Oncotype DX to intermediate Adjuvant! Online risk patients has a relatively small additional cost compared to not providing Oncotype DX, and results in a relatively large QALY gain. The incremental cost per QALY is $2,022 CAD (2.29m LBP), implying that Oncotype DX is cost-effective for intermediate Adjuvant! Online risk patients if the willingness-to-pay for a QALY is greater than 2.29m LBP. CONCLUSION: As one of the few economic evaluations to date conducted using Lebanese data, this evaluation provides information to decision makers regarding the cost-effectiveness of providing Oncotype DX to Lebanese patients.
Subject(s)
Breast Neoplasms/economics , Chemotherapy, Adjuvant/methods , Cost-Benefit Analysis/methods , Breast Neoplasms/drug therapy , Female , HumansABSTRACT
Acute myeloid leukemia (AML) is characterized by chromosomal abnormalities affecting both prognosis and course of treatment. While most AML patients have well described chromosomal aberrations, around 10% present with rare chromosomal abnormalities. We herein, report a rare balanced translocation t(12;19)(q13;q13) in a 66-year old M5-AML patient identified by Conventional cytogenetic analysis and confirmed by SNP array. We suggest that t(12;19) as a sole chromosomal abnormality could be associated with a poor prognosis. Further studies are needed to understand the molecular basis of this translocation in AML.
