High BrCa1 Expression Associated With Poor LC Prognosis

[Christine]

By Norra MacReady SEOUL, SOUTH KOREA -- September 11, 2007 -- Expression of the BrCa1 oncogene may be a clue to prognosis in patients with lung cancer, a researcher reported here at the 12th World Conference on Lung Cancer (WCLC). In an analysis of tumour samples from 126 patients with non-small cell lung cancer (NSCLC), only high BrCa1 mRNA expression and a tumour that is at stage IIIA were independently associated with short overall survival, said Rafel Rosell, MD, Chief, Medical Oncology Service, and Scientific Director of Oncology Research, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.

Conversely, Dr. Rosell and colleagues found that low BrCa1 expression was a predictor of longer survival. To determine the relationship, if any, between oncogene expression and survival, Dr. Rosell and his colleagues analysed gene expression from 126 Polish patients who had undergone complete resection for NSCLC. The BrCa1 findings were compared with those from a validation sample of 58 completely resected Italian patients with NSCLC. Gene analysis to measure BrCa mRNA was performed using real-time polymerase chain reaction. The principal cohort comprised 28 women and 98 men, with a median age of 64 years. Nearly all (94.5%) were current or former smokers. There were 93 cases of squamous cell carcinoma (73.8%) and 33 cases of adenocarcinoma (26.2%). Most of the tumours (68.3%) were at stage IB or II, and were determined to be moderately or poorly differentiated (91.8%).

Among the 40 patients with a BrCa expression level >5, median survival time was 29 months. Patients with higher levels of BrCa were still alive at the time of the analysis ([P =.01). BrCa overexpression also was associated with a shorter time to relapse. All in all, BrCa levels >5 were associated with a hazard ratio (HR) of 1.98 for shorter survival (P =.02). The risk was especially strong among patients with grade IIIA NSCLC, in whom high BrCa expression had an HR of 7.91 for shortened survival (P =.001).

By comparison, in the validation group, BrCa1 levels >12.01 were associated with an HR of 2.4 for shorter survival (P =.04).

The association between BrCa1 overexpression and shorter survival means that "BrCa1 assessment could be useful for customising adjuvant chemotherapy," Dr. Rosell said.

It has already been established that high levels of BrCa translate into decreased sensitivity to cisplatin. In those patients, therefore, "cisplatin-based chemotherapy could be a mistake."