Some BRCA1 Carriers Less Sensitive to Taxane

August 15, 2011

By David Douglas

NEW YORK (Reuters Health) Aug 12 - Taxanes are less effective in some patients with BRCA1 mutations, according to Dutch investigators.

If confirmed, the results "can have a major impact on the choice of type of (adjuvant) chemotherapy in BRCA1 mutation carriers with hormone receptor negative or triple negative breast cancer," said lead author Dr. Mieke Kriege in email to Reuters Health.

In a July 14th online paper in Cancer, Dr. Kriege and colleagues at Erasmus MC-Daniel den Hoed Cancer Center in Rotterdam note there is growing evidence from preclinical studies that sensitivity to taxanes requires a functional BRCA1 protein.

The present study, they write, "confirms the preclinical data, however, only for BRCA1-associated patients with hormone receptor (HRec)-negative and not HRec-positive breast cancer."

The researchers studied 48 patients who had received either docetaxel (Taxotere) or paclitaxel (Taxol) for metastatic breast cancer, including 35 BRCA1 carriers and 13 BRCA2 carriers. They also analyzed 95 matched controls with sporadic metastatic breast cancer.

Compared to the control group, the BRCA1 carriers had fewer objective responses (23% vs. 38%), more progressive disease (60% vs. 19%) and a shorter median progression-free survival (2.2 vs. 4.9 months).

In the subgroup of HRec-negative patients, objective response rates were 20% in BRCA1 patients and 42% in patients with sporadic disease. Seventy percent of HRec-negative BRCA carriers had disease progression, vs. 26% of controls. The mutation carriers also had a shorter progression-free survival: 1.8 vs. 3.8 months.

In the HRec-positive patients, however, outcomes were similar in BRCA1 carriers and controls.

In BRCA2-associated patients, who were mainly HRec-positive, the objective response was higher than in sporadic patients (89% vs. 38%).

If the results can be replicated, Dr. Kriege said, HRec-negative BRCA carriers might be better off with an anthracycline- or platinum-containing regimen instead of taxane chemotherapy, "which is nowadays a cornerstone in most of the adjuvant chemotherapeutic regimens."


Cancer 2011.


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