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Sep 26, 2007

BRCA1 Predicts Outcome and Response to Treatment in Lung Cancer

  • A group of European researchers report that the breast cancer susceptibility gene BRCA1 plays a significant role in non-small-cell lung cancer (NSCLC).

    Dr. Rafael Rosell explained at the European Cancer Conference (ECCO 14) in Barcelona, that analysis of the expression of five different genes had shown that those NSCLC patients who had high levels of BRCA1 had an increased risk of dying early from the disease.

    In addition, Dr. Rosell, who is chief of the medical oncology service and scientific director of oncology research at the Catalan Institute of Oncology in Barcelona, said that he and his colleagues were able to verify earlier studies that linked low levels of BRCA1 expression with high sensitivity to cisplatin-based chemotherapies and high levels of BRCA1 expression with lack of response to cisplatin, but an increased sensitivity to taxanes.

    “Our findings represent a drastic change from the currently accepted view that cisplatin-based adjuvant chemotherapy can reduce the risk of relapse in resected NSCLC patients,” Dr. Rosell noted.

    Dr. Rosell and his colleagues from Poland and Italy investigated gene expression in tumor samples from 126 patients in Poland who had received surgery for NSCLC between 2000 and 2004. In addition to BRCA1, they also looked at the expression of four other genes: nucleotide excision repair genes ERCC1 and MZF1 (myeloid zinc finger), TRX1 (thioredoxin-1), associated with poor prognosis, and TWIST1, which is involved in metastasis.

    In a statistical analysis of the results, only BRCA1 and the stage of the disease emerged as independent predictors of survival, according to the scientists. Patients with high levels of BRCA1 expression had a 1.98 higher risk of dying within three years. Patients with advanced disease at stage IIIA had a 7.91 higher risk of dying.

    Out of 77 patients with low levels of BRCA1, the majority were still alive without relapse. For the 36 patients with high levels of BRCA1, the average event-free survival was 22 months, with a range of 14.9 to 29 months. When the average overall survival was analyzed, the majority of 83 patients with low BRCA1 levels were still alive. But of 40 patients with high BRCA1 levels, average survival was 29 months, the research team reported.

    The researchers checked these findings by examining NSCLC tumor samples from a separate group of 58 Italian patients, followed up for 40 months. “Our study showed that overexpression of BRCA1 was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set from the Italian patients further strengthened this association,” Dr. Rosell said. “We suggest that patients with high BRCA1 levels will benefit from taxane-based – and not cisplatin-based – chemotherapy.”



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