Researchers at The University of Texas MD Anderson Cancer Center have discovered that when treated with Herceptin prior to surgery, 50 percent of HER2 positive, breast cancer patients showed no signs of disease at the time of surgery. However, of those women who had residual disease, about one-third had tumors that converted from HER2 positive to HER 2 negative status, possibly indicating a resistance to the targeted therapy.

Approximately 30 percent of breast cancer cells have an excess amount of the HER2 protein on their surface, which makes the cancer more aggressive.
Herceptin ( Trastuzumab ) is a monoclonal antibody that inhibits tumor growth. It was approved in 1998 for women whose advanced, metastatic mammary carcinoma is HER2-positive; it was approved in 2006 for use in the early setting.

It's known that a small percentage of HER2 positive patients develop a resistance to Trastuzumab during treatment, and there have been several described mechanisms for Herceptin resistance.

Using the MD Anderson Breast Medical Oncology database, the retrospective study identified 143 early stage and locally advanced breast cancer patients, all of whom had cancers expressed HER2 at the time of diagnosis. The women were treated with Trastuzumab, in combination with taxane- and anthracycline-based chemotherapies, prior to surgery.

At the time of surgery, 50 percent of the women achieved a pathologic complete response ( pCR ), or no evidence of breast cancer. Of those who did not achieve pCR, pre- and post-treatment tissue samples were available for 23 patients The samples were analyzed using FISH, a laboratory technique that uses fluorescent probes to detect specific DNA sequences, in this case, additional copies of the HER2 gene. Seven patients, or 30.4 percent, were found to be HER2 negative at the time of surgery.

With a median follow-up of 10.2 months, the researchers also found that two patients ( 2.8 percent ) who had achieved a pCR had recurred, compared to eight patients ( 11.3 percent ) who did not achieve a pCR. Of the second group, tumor samples were available for five; three had converted to Trastuzumab negative status.

Despite these findings, at this time, the clinical applications are limited; more research is needed before women who have a change of HER2 status not receive their scheduled Trastuzumab following surgery.

Source: University of Texas MD Anderson Cancer Center, 2008

XagenaMedicine_2008