Promising Early-Stage Breast Cancer Treatment

Newswise — A study led by a Mayo Clinic medical oncologist and conducted by the North Central Cancer Treatment Group (NCCTG) provides important new data about the effectiveness and safety of a breast cancer treatment combining chemotherapy and a drug called trastuzumab (Herceptin).

According to Mayo Clinic medical oncologist and NCCTG study chair Edith Perez, M.D., these results could change the standard of care for thousands of women with breast cancer.

"Women with HER-2 positive breast cancer had a high risk of the cancer returning and of dying from breast cancer. This intervention -- chemotherapy plus trastuzumab -- essentially changes the natural history of the disease," says Dr. Perez.

The National Cancer Institute (NCI) sponsored two large, multicenter clinical trials studying more than 3,300 women with breast cancer between February 2000 and April 2005. These two Phase III trials were conducted by NCCTG and the National Surgical Adjuvant Breast and Bowel Project (NSABP), in collaboration with other research groups throughout the United States.

Dr. Perez, from Mayo Clinic in Jacksonville, Fla., will report results from the NCCTG trial (N9831) on Monday, May 16, at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla.

The NCCTG trial is the only study that will offer new data comparing whether trastuzumab is more effective in preventing recurrence when it's given during (concurrently) or after (sequentially) chemotherapy. These findings will be important tools to help oncologists determine how to optimize trastuzumab's protective effect in the course of treating patients with HER-2 positive breast cancer.

"Our preliminary data show that sequential treatment is good, but trastuzumab given concurrently with chemotherapy yielded important trends for better results. Although longer follow-up is needed, this difference led to the recommendation that study participants who are currently receiving chemotherapy should receive trastuzumab at the same time as the paclitaxel, instead of waiting," says Dr. Perez.

Additional Background

About the Joint Analysis of the Two Trials

The NCI reported preliminary results from a joint analysis of both the NCCTG and NSABP trials on April 25, 2005. These data showed that women who received trastuzumab in combination with chemotherapy had a significant (52 percent) decrease in risk for breast cancer recurrence and a 33 percent decrease in risk of death when compared with women who received the same chemotherapy alone.

Both the NCCTG and NASBP trials studied women with an aggressive type of early-stage, operable breast cancer. All of these women had tumors that overproduce the HER-2/neu protein or gene, and their cancer had spread to the lymph nodes under the arm (regional lymph nodes) but not to other parts of the body. Both trials compared cancer recurrence among women who received chemotherapy alone and women who received a combination of chemotherapy and trastuzumab.

About the NCCTG Study Design

The NCCTG trial randomly divided study participants into three groups. Women in all three groups received adriamycin/cyclophosphamide (AC) chemotherapy followed by weekly paclitaxel, another chemotherapy agent commonly used in treating breast cancer. This treatment, called adjuvant therapy, is used to kill cancer cells that sometimes remain after surgery or other forms of initial cancer treatment.

After receiving chemotherapy, each of the three NCCTG patient groups followed a different course of treatment that allowed researchers to study the effectiveness of adding trastuzumab (Herceptin) to adjuvant therapy:* Women in Arm A, the control arm, received paclitaxel (chemotherapy) alone.* Women in Arm B, the "sequential" treatment arm, received paclitaxel, followed by trastuzumab.* Women in Arm C, the "concurrent" treatment arm, received trastuzumab along with paclitaxel.

About HER-2/neu Positive Cancers

Human epidermal growth factor receptor 2 (HER-2/neu) is a protein receptor that's produced by the HER-2/neu gene. Normally, substances that attach to this receptor stimulate cell growth. When too many of these receptors are present, they can accelerate cancer cell growth. Approximately 20 to 30 percent of breast cancers overproduce HER-2/neu.

About Trastuzumab

Trastuzumab (Herceptin) is a monoclonal antibody, a laboratory-made drug designed to attack specific cancer cells. Given intravenously (by injection), trastuzumab targets cancer cells that overproduce HER-2 proteins and slows or stops the growth of these cells. Genentech, located in South San Francisco, manufactures trastuzumab under the brand name Herceptin. In 1998, the Food and Drug Administration (FDA) approved Herceptin for the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body) in which HER-2 was overproduced.

About NCCTG

Based at Mayo Clinic in Rochester, Minn., NCCTG is a national clinical research group sponsored by the National Cancer Institute. NCCTG is a network of more than 400 community-based cancer treatment clinics in the United States, Canada and Mexico that work with Mayo Clinic to conduct clinical studies for advancing cancer treatment.

DISCLOSURE

These trials were sponsored by the National Cancer Institute (NCI) and the Breast Cancer Research Foundation, and conducted by a network of researchers led by NCCTG and NSABP in collaboration with several other cancer research groups. Genentech, Inc., manufactures trastuzumab and provided the drug for the trials under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of trastuzumab.