Combining the molecularly targeted therapy Herceptin with chemotherapy in women with early-stage breast cancer improved disease-free survival times significantly in patients with a specific genetic mutation that results in a very aggressive form of the disease, a UCLA-led study found.

The Phase II study of more than 3,200 women tested Herceptin, developed based on laboratory and clinical research conducted at UCLA’s Jonsson Cancer Center, in two different chemotherapy combinations against chemotherapy alone. The women in the study all overexpressed a gene called HER-2/neu, which causes their cancer to grow and spread quickly. Herceptin targets the genetic mutation and, when paired with chemotherapy, proved to be extremely effective in treating this high-risk patient population.

The three-armed study compared:

• The standard therapy of Adriamycin and Carboplatin followed by Taxotere (ACT)
• An experimental regimen of Adriamycin and Carboplatin followed by Taxotere and one year of Herceptin (ACTH)
• An experimental regimen of Taxotere and Carboplatin with one year of Herceptin (TCH)

Study should change treatment of early-stage breast cancer

The study tested Herceptin with and without Adriamycin, an anthracycline commonly used by oncologists to treat breast cancer but one that, when combined with Herceptin, can cause permanent heart damage. Researchers sought to determine whether they could provide a therapy as effective as ACTH without the associated cardiac problems. The study showed that the women who did not receive Adriamycin did just as well in terms of cancer survival as those who did. They also showed a five-fold decrease in significant cardiac toxicities compared to women who received Adriamycin. Additionally, some women in the ACTH arm developed leukemias, while none of the women on the non-Adriamycin arm did.

The study “demonstrated unequivocally” that the best treatment for early-stage HER-2 positive breast cancer is a non-anthracyline regimen, Taxotere and Carboplatin with one year of Herceptin, according to Dennis Slamon, M.D., director of clinical/translational research at UCLA, who led the study.

About one in four women diagnosed with breast cancer every year are HER-2 positive and have poorer prognoses and shorter survival times than those who don’t have the genetic mutation. In the United States, about 50,000 women per year can benefit from the non-anthracycline regimen. That number worldwide is about 250,000 per year.

Study results extremely encouraging

Led by Dr. Slamon and conducted by the Breast Cancer International Research Group (BCIRG), the study enrolled 3,222 women with early-stage breast cancer between April 2001 and March 2004. Patients were randomized to one of the three arms, ACT, ACTH or TCH. The data represent the second interim analysis at a three-year median follow-up.

 The study shows a survival advantage for patients in the Herceptin-containing arms with:

• 92 percent of patients in the ACTH arm still alive at four years
• 91 percent of patients in the TCH arm still alive at four years

Compared to:

• 86 percent of patients in the ACT arm still alive at four years

Risk of death was reduced by:

• 40 percent among patients in the ACTH arm
• 33 percent among patients in the TCH arm

The future: Treatment without chemotherapy?

A promising Phase II study being conducted at UCLA and in an affiliated network of oncology offices is testing two molecularly targeted therapies to treat advanced breast cancer without using conventional chemotherapy. Herceptin is being combined with Avastin, an angiogenesis inhibitor that cuts off the independent blood supply a tumor creates to help it grow and spread.

The study enrolled 37 women with breast cancer that had spread to other organs, the hardest type to treat effectively. Early results indicate that 83.8 percent of patients showed a clinical response, with tumors completely disappearing, shrinking in size by more than 50 percent or remaining stable, meaning their cancers did not progress. The responses, Dr. Slamon says, “are as good as anything we’ve seen in this group of patients, even with our best chemotherapies.”

Patient referral

Appointments may be made by calling the new patient liaison office at (310) 206-6909 or (310) 206-6931.

Program leaders

Dennis Slamon, M.D.
Director of Clinical/Translational Research
Professor of hematology/oncology

John Glaspy, M.D.
Professor of hematology/oncology

Robin Farias-Eisner, M.D.
Professor of obstetrics and gynecology

Web resource