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Targeting HER2 in the Treatment of Ductal Carcinoma in Situ

Name of the Trial

Phase III Randomized Study of Radiotherapy with Versus without Trastuzumab (Herceptin) in Women with HER2-Positive Ductal Carcinoma In Situ Who Underwent Lumpectomy (NSABP-B-43). See the protocol summary.

Principal Investigators

Dr. Melody Cobleigh
Dr. Melody Cobleigh
Principal Investigator

Dr. Melody Cobleigh, Dr. Douglas Arthur, and Dr. Thomas Julian, National Surgical Adjuvant Breast and Bowel Project

Why This Trial Is Important

Ductal carcinoma in situ (DCIS), a condition in which abnormal cells are confined entirely to the milk duct of the breast, is a risk factor for the development of invasive breast cancer. The standard treatment for DCIS is surgery, which produces excellent long-term disease-free results. Although most patients can be treated with lumpectomy (breast-conserving surgery, in which only part of the breast is removed) and radiation therapy, patients with larger tumors or tumors with high-grade features may undergo mastectomy (removal of as much of the breast as possible).

One high-grade feature seen in some DCIS tumors is overexpression of the HER2 protein. When there is too much of this human epidermal growth factor receptor, tumors tend to grow faster and are also more likely to recur after initial treatment. Trastuzumab (Herceptin) is a monoclonal antibody that binds to the HER2 receptor and interferes with the growth of HER2-expressing tumors. It is approved by the FDA to be used with chemotherapy to treat HER2-positive invasive breast cancer. In addition, laboratory and animal studies have suggested that trastuzumab can increase the effectiveness of radiation therapy.

In this clinical trial, women with HER2-positive DCIS will be treated with lumpectomy followed by whole-breast radiation therapy; half of the women will also receive two doses of trastuzumab during their radiation treatment. The researchers will then monitor the women in both groups to see whether trastuzumab prevents or delays the development of invasive breast cancer or the recurrence of DCIS in the breast, among other outcomes, such as breast cancer in the opposite breast. Trastuzumab is administered for a short period of time (with radiation) and without chemotherapy, so the side effects from trastuzumab are expected to be minimal.

"We are looking for ways to extend the option of breast-conserving surgery to women whose more aggressive or advanced DCIS would normally indicate a mastectomy," said Dr. Cobleigh. "We have seen that radiation therapy can significantly improve protection after lumpectomy.

"Trastuzumab has been proven safe and effective in the treatment of both early and metastatic breast cancer, and we want to see if it can make HER2-expressing tumor cells more sensitive to radiation. These women are more likely to have aggressive DCIS, and they should have an alternative to mastectomy," she said. "This is a targeted approach that could make a real difference for women in that group."

For More Information

See the lists of entry criteria and trial contact information or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

  • Posted: October 6, 2009