This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical-pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

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Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs’ safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.

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