Patterns of Mutation Enrichment in Metastatic Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive biology and complex tumor evolution. Our purpose was to identify enrichment patterns of genomic alterations in metastatic triple-negative breast cancer (mTNBC). METHODS: Genomic data were retrieved (mutations and copy number variations) from 550 primary TNBC tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) data sets and 58 mTNBC tumors from "Mutational Profile of Metastatic Breast Cancers" and "The Metastatic Breast Cancer Project." Statistical analysis of microarray data between primary and metastatic tumors was performed using a chi-square test, and the percentage of mutation enrichment in mTNBC cases was estimated. P-values were adjusted for multiple testing with Benjamini-Hochberg method with a false-discovery rate (FDR) <.05. In addition, we identified dominant hallmarks of cancer in mTNBC. RESULTS: Seven genes with mutations were enriched in mTNBC after correcting for multiple testing. These included TTN, HMCN1, RELN, PKHD1L1, DMD, FRAS1, and RYR3. Only RPS6KB2 amplification was statistically significant in mTNBC; on the contrary, deletion of the genes TET1, RHOA, EPHA5, SET, KCNJ5, ABCG4, NKX3-1, SDHB, IGF2, and BRCA1 were the most frequent. The molecular alterations related to the hallmark of "genetic instability and mutation" were predominant in mTNBC. Interestingly, the hallmark of "activating immune destruction" was the least represented in mTNBC. CONCLUSION: Despite the study limitations, we identified recurrent patterns of genomic alterations with potential contribution to tumor evolution. Deletions were the aberrations more commonly found in mTNBC. Several molecular alterations are potentially targetable.

Precision medicine for locally advanced breast cancer: frontiers and challenges in Latin America.

Advances in high-throughput technologies and their involvement in the 'omics' of cancer have made possible the identification of hundreds of biomarkers and the development of predictive and prognostic platforms that model the management of cancer from evidence-based medicine to precision medicine. Latin America (LATAM) is a region characterised by fragmented healthcare, high rates of poverty and disparities to access to a basic standard of care not only for cancer but also for other complex diseases. Patients from the public setting cannot afford targeted therapy, the facilities offering genomic platforms are scarce and the use of high-precision radiotherapy is limited to few facilities. Despite the fact that LATAM oncologists are well-trained in the use of genomic platforms and constantly participate in genomic projects, a medical practice based in precision oncology is a great challenge and frequently limited to private practice. In breast cancer, we are waiting for the results of large basket trials to incorporate the detection of actionable mutations to select targeted treatments, in a similar way to the management of lung cancer. On the other hand and paradoxically, in the 'one fit is not for all' era, clinical and genomic studies continue grouping our patients under the single label 'Latin American' or 'Hispanic' despite the different ancestries and genomic backgrounds seen in the region. More regional cancer genomic initiatives and public availability of this data are needed in order to develop more precise oncology in locally advanced breast cancer.