Identification of HER-2/neu overexpression and the clinical course of lung carcinoma in non-smokers with chronic lymphocytic leukemia

Patients with CLL have an excess risk of developing second primary malignancies. The etiology of this excess risk is unclear, and has been thought to be related to smoking. HER-2/neu overexpression has evolved as a prognostic/predictive factor in some solid tumors. We reviewed our experience with non-smokers who had CLL and subsequently developed lung carcinoma, in an effort to better understand the clinical course of these patients, and to evaluate the role of HER-2/neu overexpression. We reviewed the records of all patients who had a diagnosis of both CLL and lung carcinoma between 1986 and 2000. HER-2/neu overexpression was estimated by immunohistochemistry (IHC) using the Hercep test (DAKO®). An IHC score of 2+ or greater was considered positive. Overall survival was calculated from the date of diagnosis of lung carcinoma by the Kaplan-Meier product limit method. Fourteen non-smokers in whom a diagnosis of CLL was made at least 6 months prior to the diagnosis of lung carcinoma were identified. The median age for diagnosis of CLL in this group was 67 years while that for lung carcinoma was 70 years. The lung carcinomas included 10 non-small cell (NSCLC) and four small cell (SCLC) carcinomas. Nine specimens (six NSCLC and three SCLC) showed HER-2/neu overexpression. Interestingly, 90% of patients with advanced stage cancer (stage IIIB/IV NSCLC or extensive SCLC) overexpressed HER-2/neu. The presence of CLL did not alter outcome in patients with early stage lung cancer. However, after adjustment for age and performance status, patients with advanced stage NSCLC and CLL had a worse than expected outcome. HER-2/neu overexpression (independent of smoking) may be involved in the development/progression of lung cancer in patients with CLL, and has an associated worse outcome. It is appropriate to consider heightened surveillance of CLL patients for lung carcinoma.