Tuesday, September 6, 2011

Chemotherapy before surgery gives big boost to women with BRCA1 gene

Women with the BRCA1 gene mutation
are more likely to achieve a complete
response with chemotherapy before
surgery. (Photo courtesy NCI.)
SEPT. 6, 2011 (CancerDigest) – If there is a silver lining to being a woman with the BRCA1 gene mutation that increases the risk of breast cancer, it is that they also have a good chance of responding to therapy. Almost half the women with the BRCA1 gene mutation who underwent chemotherapy before surgery achieved a complete response, meaning disappearance of all cancer based on microscopic examination of tissue samples in a recent study.

The study, led by Dr. Banu Arun, professor in the Department of Breast Medical Oncology at MD Anderson Cancer Center, is the largest to date to find that complete response rate is significantly higher in women with the BRCA1 mutation than for women with BRCA2 mutations. The study showed that 46 percent of the BRCA1 women achieved the complete response compared to 13 percent of those with BRCA2, and 22 percent of women without either gene mutation. The study was published online Sept. 6, 2011 in The Journal of Clinical Oncology.

"While hereditary breast cancers typically carry aggressive tumor features compared to sporadic breast cancers, we found that BRCA1-related tumors were as responsive and sensitive to anthracycline and taxane-based chemotherapy as were sporadic breast cancers," Arun said in a prepared statement. "These findings may help physicians determine the best treatment method for this subset of women with unique genetic mutations."

The study looked at data of 317 women treated for breast cancer at MD Anderson at a variety of stages, and who received neoadjuvent chemotherapy and clinical genetic testing for BRCA1 and BRCA2 between 1997 and 2009. Fifty- seven women were BRCA1 carriers, 23 were BRCA2 mutation carriers and 237 were non-carriers. After chemotherapy, 61 patients received breast-conserving surgery, while 256 opted for mastectomy.

BRCA1 and BRCA2 belong to a class of human genes known as tumor suppressors. The mutation is inherited and increases a woman's chance of developing breast cancer with more aggressive features by 80 percent. Researchers aimed to determine whether women with and without the mutations would respond differently to the same treatment.

After following the women for a median of 3.2 years, 22 percent  experienced disease recurrence or death. There were no significant differences noted in survival outcomes with respect to BRCA status and type of neoadjuvent chemotherapy received.

According to Arun, there is no consensus on the most effective chemotherapy regimen for treating women who carry the BRCA mutation, due to a lack of studies comparing the treatments given women with the genetic mutations as they progress through treatment and follow-up.

"This new insight tempts us to speculate that the presence of the BRCA1 mutation determines how some women will respond to neoadjuvent chemotherapy. However, we need future prospective studies with larger cohorts and longer-term follow up to validate these findings and determine optimum treatment," Arun noted.

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