According to Dutch researchers, BRCA2-associated cancer patients are more sensitive to standard first-line chemotherapy for metastatic disease than patients with sporadic breast cancer.
Based on preclinical and other studies, Dr. Mieke Kriege of the Rotterdam Family Cancer Clinic and colleagues reported that breast cancer cells without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents.
To know further, the researchers retrospectively investigated 93 patients with BRCA1 and 28 with BRCA2-associated breast cancer. All patients had chemotherapy for metastatic disease before January 1, 2007. The study used chemotherapy regimens like anthracycline-based and cyclophosphamide, methotrexate, and fluorouracil.
The outcomes of these patients were compared with those of matched patients with sporadic disease. It was found that median progression-free survival for the BRCA2 patients was 11.4 months which is significantly longer than the 6.7 months seen in the sporadic group. BRCA1 patients had slightly greater, but not significant, median survival of 7.6 months.
The rates of overall survival were same, with a median of 19.3 months in BRCA2 patients, 13.6 months in sporadic patients and 15.0 months in BRCA-1 patients.
We observed a significantly increased chemosensitivity to first-line standard chemotherapy for metastatic breast cancer in BRCA2-mutation carriers as compared to sporadic patients accompanied by a significantly increased overall survival, the researchers conclude.
For BRCA1-mutation carriers, they add, there was a trend towards a better response rate and clinical benefit as well as longer progression-free survival.
Dr. Kriege added that the observation of the high efficacy of anthracycline-based regimens is especially reassuring. However, larger additional studies are urgently needed to investigate further newer combination regimens to make firm conclusions about the efficacy of different treatment regimens in BRCA1/2 mutation carriers.