BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.

Breast tumor heterogeneity is a major challenge in the clinical management of breast cancer patients. Both inter-tumor and intra-tumor heterogeneity imply that each breast cancer (BC) could have different prognosis and would benefit from specific therapy. Breast cancer is a dynamic entity, changing during tumor progression and metastatization and this poses fundamental issues to the feasibility of a personalized medicine approach. The most effective therapeutic strategy for patients with recurrent disease should be assessed evaluating biopsies obtained from metastatic sites. Furthermore, the tumor progression and the treatment response should be strictly followed and radiogenomics and liquid biopsy might be valuable tools to assess BC heterogeneity in a non-invasive way.

Background. Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy. Methods. In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay. Results. The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%). Conclusions. The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.

An increasing number of driver genomic alterations with potential targeted treatments have been identified in non-small cell lung cancer (NSCLC). Much less is known about the incidence and different distribution of concurrent alterations, as identified by comprehensive genomic profiling in oncogene-addicted NSCLCs. Genomic data from advanced NSCLC consecutively analyzed using a broad next-generation sequencing panel were retrospectively collected. Tumors harboring at least one main actionable gene alteration were categorized according to the presence/absence of concurrent genomic aberrations, to evaluate different patterns among the main oncogene-addicted NSCLCs. Three-hundred-nine actionable gene alterations were identified in 284 advanced NSCLC patients during the study period. Twenty-five tumor samples (8%) displayed concurrent alterations in actionable genes. Co-occurrences involving any pathogenic variant or copy number variation (CNV) were identified in 82.8% of cases. Overall, statistically significant differences in the number of concurrent alterations, and the distribution of TP53, STK11, cyclines and receptor tyrosin kinase (RTK) aberrations were observed across the eight actionable gene groups. NGS analyses of oncogene-addicted NSCLCs showed a different distribution and pattern of co-alteration profiles. Further investigations are needed to evaluate the prognostic and treatment-related impact of these concurrent alterations, hooked to the main gene aberrations.

Dear Editor, Milan, the largest city in northern Italy, was one of the first European metropolitan areas to be affected by the coronavirus disease 2019 (COVID‐19) pandemic. We analysed skin biopsies of patients from Milan with dermatoses and positive polymerase chain reaction (PCR) swabs for SARS‐CoV‐2 at different stages of infection. ¹, ² The results were compared with skin biopsies of 20 patients with dermatoses who had not been diagnosed with COVID‐19, but were at high risk of infection. They were considered high risk because they either presented with mild COVID‐19 symptoms or had been in close contact with individuals who were positive for SARS‐CoV‐2. Histopathological features and patterns showed no differences between these two groups. Furthermore, 70% of the skin samples from the ‘high‐risk’ group were immunohistochemically positive for SARS‐CoV‐2 nucleocapsid antigens. ²