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BRCA1 overexpression is strongly linked to poor outcome in NSCLC patients treated with cisplatin

BRCA1 overexpression is strongly linked to poor outcome in NSCLC patients treated with cisplatin

BARCELONA, Spain—Researchers have found that the breast cancer susceptibility gene BRCA1 plays a significant role in non-small-cell lung cancer. Not only can it be used to predict outcome for patients with NSCLC but it also may prove to be a valuable tool in choosing the best therapy.

Speaking at the 14th European Cancer Conference (ECCO abstract 6506), Rafael Rosell, MD, said that analysis of the expression of five different genes had shown that those NSCLC patients who had high levels of expression of BRCA1 had nearly double the risk of dying early from the disease, compared with patients with low levels of BRCA1 expression.

Dr. Rosell is chief of the Medical Oncology Service and scientific director of oncology research at the Catalan Institute of Oncology in Barcelona.

He said that earlier studies in breast cancer and a study by him and his colleagues in NSCLC had linked low levels of BRCA1 expression with high sensitivity to cisplatin-based chemotherapies, while high levels of BRCA1 expression were linked with lack of response to cisplatin but an increased sensitivity to antimicrotubule agents (taxanes) that prevent tumor growth by stopping cell division.

"Our research shows that patients whose tumors had high BRCA1 expression had significantly worse survival and should be candidates for adjuvant chemotherapy," Dr. Rosell said.

Earlier studies, he said, have shown how different levels of BRCA1 expression affect response to different types of chemotherapy. "Therefore, we believe that BRCA1 could be a landmark predictor of chemosensitivity in NSCLC, and assessment of its expression could be useful for customizing adjuvant chemotherapy," Dr. Rosell said. "We believe that patients with the highest expression levels should receive antimicrotubule, nonplatinum-based chemotherapy."

Five genes analyzed

Dr. Rosell and his colleagues from Poland and Italy investigated gene expression in frozen tumor samples from 126 patients in Poland who had undergone 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), which is associated with poor prognosis; and TWIST1, which is involved in metastasis.

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