Comparative Genomic Profiling of Second Breast Cancers following First Ipsilateral Hormone Receptor-Positive Breast Cancers.

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.

Total Parenteral Nutrition in Middle Eastern Cancer Patients at End of Life: Is it Justified?

PURPOSE: The use of total parenteral nutrition (TPN) in terminally ill cancer patients is considered an aggressive approach with very limited benefits. We examined the practice of TPN in our end of life cancer patients and we investigated the patient and tumor characteristics that justify this practice. To our knowledge, this is the first study describing TPN administration of Middle Eastern patients with advanced cancer. METHODS: We conducted this retrospective observational study at Hotel-Dieu de France University Hospital, Lebanon. Eligible cases included all cancer patients that died at our institution between the 1st of January and the 31st of December 2014. The patients and tumors characteristics were analyzed for their potential role as determinant of TPN administration. The patients' hospitalization and causes of death were evaluated for the analysis of TPN benefits. RESULTS: Among the 129 patients enrolled, 39% had received TPN among which TPN administration correlated negatively to hyperlipidemia (OR= 0.33; 95% CI [0.12-0.87]) and to the presence of at least three cardiovascular risk factors (OR= 0.28; 95% CI [0.10 - 0.80]). However, it correlated positively to gastrointestinal tumors (OR= 3.9; 95% CI [1.3- 11.7]) and to imaging studies during the last month of life (OR= 3.4; 95% CI [1.3 - 9.0]). The TPN administration did not correlate to hospitalization during the last two weeks of life. CONCLUSION: The adoption of an optimal palliative care approach in Middle Eastern cancer patients at the end of life remains challenging. Oncologists seem to consider cardiovascular risk factors as a probable surrogate to predict complications of TPN.