Influence of Sex in the Molecular Characteristics and Outcomes of Malignant Tumors.

BACKGROUND: Sex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer. METHODS: A cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC). RESULTS: Overall, women had a decreased risk of death (HR = 0.73, CI95: 8%-42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men. CONCLUSIONS: The study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.

The hispanic landscape of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and complex disease characterized by the absence of immunohistochemical expression of estrogen receptor, progesterone receptor and HER2. These breast tumors present an aggressive biology and offer few opportunities to be treated with targeted therapy resulting in bad disease outcomes. The epidemiology of TNBC is intriguing where the understanding of its biology has progressed quickly. One of the peculiarities of this type of cancer is a high prevalence in Afrodescendants and Hispanic patients compared to Caucasian women. In this review we describe some features of TNBC, focusing in the Hispanic population, such as epidemiological, clinicopathological features and molecular features and the correlation between TNBC prevalence and the human development index.

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.