BRCA1 mRNA expression in patients with bladder cancer treated with neoadjuvant cisplatin-based chemotherapy
Improved overall survival has been demonstrated with the use of cisplatin-based chemotherapy given prior to radical cystectomy in patients with locally advanced bladder cancer, as compared to radical cystectomy alone (Lancet, 2003). Although the majority of patients who are planned to undergo radical cystectomy receive cisplatin-based chemotherapy, no tumor or clinical marker currently exists to predict whether they will benefit from this treatment. Avoidance of platinum-based chemotherapy in patients with a decreased likelihood of benefit from these agents would be helpful.
Mutations in the BRCA1 gene (breast cancer susceptibility gene 1) have been associated with both increased risk of development of certain cancers, and resistance to chemotherapy. Overexpression of BRCA1 mRNA has recently been demonstrated to be predictive of in vitro (in the laboratory) sensitivity to cisplatin and docetaxel in metastatic lung, gastric and ovarian cancers. This study evaluates the role of overexpression of BRCA1 mRNA in bladder cancer patients with regard to response to treatment, disease-free survival, and overall survival.
98 patients with varying stages of disease were evaluated. Tumor tissue was tested and BRCA1 mRNA levels were found to be low in 35% of patients, intermediate in 32%, and high in 32%. Response to the chemotherapy was seen in 66% of patients with low or intermediate levels but only 23% of patients with high levels. Disease-free survival (that is, survival without any recurrence) was strongly correlated to the BRCA1 mRNA levels. DFS was 120 months in patients with low BRCA1 mRNA levels, 184 months in those with intermediate levels, and 14 months in those with high levels. Five-year overall survival (that is, survival with or without recurrence) was 63% in patients with low or intermediate BRCA1 mRNA expression, and 23% in those with high levels.
While this study suggests that BRCA1 mRNA levels can be used to predict response to cisplatin therapy, a randomized trial could be indicated to evaluate this as well as the response to taxane therapy for those with high expression levels.