The use of next-generation sequencing (NGS) techniques for variant detection has become increasingly important in clinical research and in clinical practice in oncology. Many cancer patients are currently being treated in clinical practice or in clinical trials with drugs directed against specific genomic alterations. In this scenario, the development of reliable and reproducible bioinformatics tools is essential to derive information on the molecular characteristics of each patient’s tumor from the NGS data. The development of bioinformatics pipelines based on the use of machine learning and statistical methods is even more relevant for the determination of complex biomarkers. In this review, we describe some important technologies, computational algorithms and models that can be applied to NGS data from Whole Genome to Targeted Sequencing, to address the problem of finding complex cancer-associated biomarkers. In addition, we explore the future perspectives and challenges faced by bioinformatics for precision medicine both at a molecular and clinical level, with a focus on an emerging complex biomarker such as homologous recombination deficiency (HRD).

Several studies have explored the prognostic role of hormone receptor status in high-grade serous ovarian cancer (HGSOC) patients. However, few reports have investigated their expression according to BRCA mutational status. The aim of this single-center, observational, retrospective study was to explore the hormone receptor pattern and its potential prognostic role in a cohort of 207 HGSOC women stratified for BRCA mutational status. To this end, ERα, ERβ1, ERβ2, ERβ5, PR, and AR expression were assessed by immunohistochemistry in 135 BRCA-wild type (BRCA-wt) and 72 BRCA1/2 mutation carriers (BRCA-mut). No significant difference emerged in hormone receptor expression between the two sub-samples, except for a significantly lower ERα expression observed in pre-menopausal BRCA1/2-mut as compared to BRCA-wt patients (p = 0.02). None of the examined hormone receptors has revealed a significant prognostic role in the whole sample, apart from the ratio ERα/ERβ5 nuclear, for which higher values disclosed a positive role on the outcome in BRCA-wt subgroup (HR 0.77; CI 0.61–0.96; p = 0.019). Conversely, it negatively affected overall survival in the presence of BRCA1/2-mut (HR 1.41; CI 1.06–1.87; p = 0.020). Finally, higher PR levels were associated with platinum sensitivity in the whole sample (p = 0.019). Our data, though needing further validation, suggest a potential role of oestrogen-mediated pathways in BRCA1/2-associated HGSOC tumorigenesis, thus revealing a possible therapeutic potential for targeting this interaction.