BioCAST/IFCT-1002: epidemiological and molecular features of lung cancer in never-smokers

Abstract

Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular features of LCINS in Europe remain poorly understood.All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences.384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35%versus8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference):EGFRin 51%,ALKin 8%,KRASin 6%,HER2in 3%,BRAFin 3%,PI3KCAin less than 1%, and multiple in 2%.We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%).

No impact of passive smoke on the somatic profile of lung cancers in never-smokers

“…Similar results have been found for exposure in the workplace and during childhood [4,5]. In a recent French study, we reported that 66% of LCINSs had been exposed to passive smoke, especially women and those exposed in domestic settings [6,7].…”

“…Similar concerns may occur for the PSY variable. In addition, the population in which the studies were conducted differed from study to study, ranging from Asian only [13,14,16] to primarily Caucasian [7,15], and from never-smoker only [13,14] to all smoking statuses mixed [16]. These differences may also account for the conflicting results, as genomic susceptibility and confounding related to risk-factor exposure could differ depending on geographical origin [2,25].…”

“…The study design has been reported elsewhere [18] and our principal results appear in this issue of the European Respiratory Journal [7]. Briefly, BioCAST is a prospective, multicentre, observational study designed to describe the clinical, pathological and molecular epidemiology of LCINS in a French population.…”

Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002

“…BioCAST is a prospective, multicentric cohort sponsored by the French intergroup IFCT, designed to describe clinical, pathologic, and molecular epidemiology of LCINS in a French population. The detailed protocol is reported elsewhere (24). Briefly, newly diagnosed cases of NSCLC from self-declared nonsmokers were included and surveyed.…”

Lung cancer in never-smokers

“…These rates were similar to the largest ever cohort of East Asian NSCLC never-smokers, reported by KIM et al [19], which observed 229 tumours; the frequency of EGFR mutations, ALK rearrangements, KRAS mutations and no mutations was 48%, 8.3%, 3.5%, and 40.2%, respectively. The gene modification frequencies reported by COURAUD et al [12] are slightly different from those seen in the Biomarker France study (preliminary results on 9911 NSCLC patients): EGFR (33%), KRAS (9.6%), BRAF (1.8%), PI3K (3.6%), HER2 (3.8%) mutations and ALK rearrangements (9.7%) in never-smokers (17.7% of the tested NSCLC patients) [20]. No mutations were reported in 35.2% of never-smokers in the Biomarker France study, compared to 27% in the present study.…”