Adverse events during treatment of nontuberculous mycobacterial lung disease: do they really matter?

28th International Congress of the European-Respiratory-Society (ERS), Paris, FRANCE, SEP 15-19, 2018International audienceTreatment of nontuberculous mycobacterial lung disease (NTM LD) is long and hampered with frequent adverse events. Side effects may explain the poor prognosis associated with this disease. Our hypothesis was that adverse events might be responsible of premature discontinuation of treatment, thus leading to an increased mortality. We conducted a retrospective study including adult patients treated for NTM LD at 5 French hospitals between January 1st 2010 and December 31st 2015. Patients with cystic fibrosis were excluded. 71 patients were included, of which 45 had a pulmonary disease due to Mycobacterium avium complex and 15 due to M. xenopi. All patients fulfilled the ATS clinical and microbiological criteria for NTM LD. While treated, 72% of patients presented at least one reported side effect, of which 65% were gastro-intestinal and 21% were ophthalmologic. 14 patients stopped prematurely their treatment while initial therapy was modified in 22 cases due to poor tolerance. Adverse events were more common in patients who had been previously treated for NTM LD (p=0.02). Early treatment cessation was associated with the absence of sputum conversion (p=0.014) but not with mortality (p=0.237). Occurrence of adverse events was not associated with mortality. 15 patients died, among them 6 were under treatment. Mortality was associated with use of systemic steroids and existence of comorbidities, especially pulmonary or cardiovascular ones, as well as extra pulmonary cancers. Side effects of drugs used to treat NTM LD are common and responsible for early cessation of treatment that may result in a lack of sputum conversion. However, they did not affect mortality in our cohort

Author Correction: Genomic characterization of metastatic breast cancers

International audienceAn Amendment to this paper has been published and can be accessed via a link at the top of the paper

Genomic characterization of metastatic breast cancers

International audienceMetastasis is the main cause of death for patients with breast cancer. Many studies have characterized the genomic landscape of breast cancer during its early stages. However, there is evidence that genomic alterations are acquired during the evolution of cancers from their early to late stages, and that the genomic landscape of early cancers is not representative of that of lethal cancers1-7. Here we investigated the landscape of somatic alterations in 617 metastatic breast cancers. Nine driver genes (TP53, ESR1, GATA3, KMT2C, NCOR1, AKT1, NF1, RIC8A and RB1) were more frequently mutated in metastatic breast cancers that expressed hormone receptors (oestrogen and/or progesterone receptors; HR+) but did not have high levels of HER2 (HER2-; n = 381), when compared to early breast cancers from The Cancer Genome Atlas. In addition, 18 amplicons were more frequently observed in HR+/HER2- metastatic breast cancers. These cancers showed an increase in mutational signatures S2, S3, S10, S13 and S17. Among the gene alterations that were enriched in HR+/HER2- metastatic breast cancers, mutations in TP53, RB1 and NF1, together with S10, S13 and S17, were associated with poor outcome. Metastatic triple-negative breast cancers showed an increase in the frequency of somatic biallelic loss-of-function mutations in genes related to homologous recombination DNA repair, compared to early triple-negative breast cancers (7% versus 2%). Finally, metastatic breast cancers showed an increase in mutational burden and clonal diversity compared to early breast cancers. Thus, the genomic landscape of metastatic breast cancer is enriched in clinically relevant genomic alterations and is more complex than that of early breast cancer. The identification of genomic alterations associated with poor outcome will allow earlier and better selection of patients who require the use of treatments that are still in clinical trials. The genetic complexity observed in advanced breast cancer suggests that such treatments should be introduced as early as possible in the disease course