BRCA2 BREAST CANCER MORE SENSITIVE TO CHEMOTHERAPY

NEW YORK (Reuters Health) Jul 17 - Compared with patients with sporadic breast cancer, those with BRCA2-associated cancer are more sensitive to standard first-line chemotherapy for metastatic disease, Dutch researchers report in the June 29th issue of the Journal of Clinical Oncology.

Dr. Mieke Kriege of the Rotterdam Family Cancer Clinic and colleagues note that a number of preclinical and other studies have suggested that breast cancer cells without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents.

To examine whether this might have any clinical impact, the researchers retrospectively studied data on 93 patients with BRCA1- and 28 with BRCA2-associated breast cancer. All were treated with chemotherapy for metastatic disease before January 1, 2007. The most frequently used chemotherapy regimens used were anthracycline-based and cyclophosphamide, methotrexate, and fluorouracil.

Patient outcomes were compared with those of matched patients with sporadic disease. The BRCA2 patients had a median progression-free survival of 11.4 months, significantly longer than the 6.7 months seen in the sporadic group. BRCA1 patients had slightly greater median survival (7.6 months), but this did not reach significance.

The rates of overall survival were similar, 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."

In comments to Reuters Heath, 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."

J Clin Oncol 2009;27.