ECCO: Herceptin Pre-Surgery More Effective Than Chemo Alone in Inflammatory Breast CA

BARCELONA, Spain, Sept. 26 -- The addition of trastuzumab (Herceptin) to chemotherapy before surgery appears to allow more women with HER-2 positive inflammatory breast cancer to achieve a complete disease response than does chemotherapy alone.

In a study of 76 women with the relatively rare, but rapidly progressing disease, researchers said that tumors disappeared completely in the breast in 54.8% of HER-2 positive women who received trastuzumab and standard doxorubicin-paclitaxel and cyclophosphamide chemotherapy compared with only 19.3% of HER-2 positive women who received just the chemotherapy (P=0.004).

"This is the first randomized study to demonstrate the benefit of adding trastuzumab to neoadjuvant therapy in this subgroup of patients," Jose Baselga, M.D., of the Vall d'Hebron University Hospital here, told attendees at the European CanCer Organisation meeting.

"The results are particularly meaningful to patients, as receiving trastuzumab in this setting could lead to more breast conserving surgery and even translate into improved survival," he said.

In addition to an improved ability to eliminate tumors in the breast, 48.4% of the 31 HER-2 positive women given trastuzumab also achieved a complete clearance of tumors cells in the lymph nodes compared with 12.9% of the 31 HER-2 positive women not given trastuzumab (P=0.002).

There were 14 women in the study who had inflammatory breast cancer but did not overexpress the HER-2 gene. These women were given chemotherapy but not trastuzumab. In that small group, 28.6% achieved complete responses in both the breast and the lymph nodes.

Trastuzumab is designed to interfere with the molecular cascade that occurs in breast cancer, allowing cytotoxic drugs to be more efficient.

In this substudy of the NOAH (Neoadjuvant Herceptin) trial, patients were randomized on a one-to-one basis after being diagnosed with breast cancer. The women who tested negative for HER-2 were given similar chemotherapy treatment as the chemotherapy arm: Three cycles of doxorubicin 60 mg/m2 with paclitaxel 150 mg/m2 every three weeks; four cycles of paclitaxel 175 mg/m2 every three weeks; three cycles of cyclophosphamide 600 mf/m2/5-fluorouracil 600 mg/m2 and methotrexate 40 mg/m2 every four weeks.

Trastuzumab, given only to the women who overexpressed HER-2, was supplied to patients for a year. Women were first given a loading dose of 8 mg/kg and then were given 6 mg/kg every three weeks.

The NOAH study will continue to follow the women to determine if the impact of trastuzumab seen in the initial treatment stages translates into event-free survival benefits for the patients.

The study involving inflammatory breast cancer is a substudy of a larger trial that has enrolled 228 women with HER-2 positive locally advanced breast cancer and 99 women with HER-2 negative locally advanced breast cancer.

"The results seen in this study are consistent with what we see in clinical practice with women who have inflammatory breast disease," said Ian Krop, M.D., Ph.D., of the Dana-Farber Cancer Institute and Harvard Medical School.

"Herceptin does appear to help women with inflammatory breast cancer respond to treatment. We need studies like this to help us determine the best way the treat women with this disease. There is no established standard."

The NOAH trial is being supported by Roche.

Neither Dr. Baselga nor Dr. Krop disclosed possible financial conflicts of interest.