A new study indicates that a regimen of trastuzumab and paclitaxel can prevent the recurrence of HER2-positive breast cancer. Of 406 women who received the drugs after surgery for stage I disease, 99.2% survived 3 years without a recurrence.

The most effective way to prevent small, HER2-positive breast tumors from recurring after surgery has been unclear. A new study supports using a combination of trastuzumab (Herceptin; Genentech) and paclitaxel (Taxol; Bristol-Myers Squibb) that is less toxic than the therapy many patients receive.

For women whose stage I, HER2-positive breast tumors have not spread to the lymph nodes, one postsurgical option is no treatment. Studies that followed patients for up to 10 years, however, suggest that the cancer will recur 5% to 30% of the time. Thus, some doctors favor hitting any remaining cancer cells hard with a combination such as doxorubicin, cyclophosphamide, trastuzumab, and paclitaxel. However, the side effects of such regimens, which can include vomiting, neuropathy, and congestive heart failure, are sometimes severe.

Trastuzumab-containing regimens have reduced breast cancer recurrence in previous trials, but these studies included mainly patients with stage II or stage III HER2-positive tumors. A team led by Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, MA, reasoned that combining trastuzumab with paclitaxel, which is less toxic than drugs such as doxorubicin, might also work for stage I tumors and would cause fewer side effects than conventional treatments. Winer and colleagues gave standard doses of the two drugs to 406 women whose HER2-positive tumors were less than 3 centimeters in diameter at the time of removal. The patients received trastuzumab every week for a year and paclitaxel every week for 3 months.

The researchers did not include a control group in the study, Winer says, because they assumed that patients wouldn't want to participate if they didn't receive trastuzumab. However, Dennis Slamon, MD, PhD, of the University of California, Los Angeles, faults the work for lacking a head-to-head comparison of the trastuzumab–paclitaxel combination versus trastuzumab and a different chemotherapy.

After 3 years, tumors had recurred in six patients. In four patients, the tumors were local or regional—in the breast or armpit—and in two patients, they appeared elsewhere in the body. However, 79 patients left the study because of side effects or other reasons, or they couldn't be located for follow-up. Because of these drop outs, the team used a statistical technique to calculate the rate of tumor recurrence. This analysis revealed a 3-year rate of recurrence-free survival of 99.2%, the researchers reported in January in The New England Journal of Medicine.

Side effects from the treatment included hair loss, fatigue, and neuropathy, but serious problems were rare. The rate of congestive heart failure, for example, was 0.5%, less than one fifth the rate recorded in an earlier study of a doxorubicin, cyclophosphamide, trastuzumab, and paclitaxel combination treatment in women with more advanced HER2-positive breast tumors.

Winer and colleagues conclude that trastuzumab and paclitaxel should be an option for patients with HER2-positive stage I breast cancer. Because of the study's results, Winer says, Dana-Farber Cancer Institute has switched to trastuzumab and paclitaxel.