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Preop Chemotherapy May Have Advantages in Primary Breast Cancer

Preop Chemotherapy May Have Advantages in Primary Breast Cancer

ASCO--A brief, intensive preoperative chemotherapeutic regimen failed to improve breast cancer survival over conventional adjuvant chemotherapy in a 1,500-patient randomized trial, Dr. Eleftherios Mamounas said for the National Surgical Adjuvant Breast Project (NSABP). However, preoperative treatment often resulted in complete clinical remission prior to surgery.

Moreover, Dr. Mamounas said, the initial response to preoperative chemotherapy correlated with disease-free survival, suggesting that preoperative treatment may provide useful prognostic information to guide follow-up therapy.

The NSABP investigators compared the efficacy of short-term intensive preoperative chemotherapy with doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) given every three weeks for four cycles versus the same regimen after surgery. Women age 50 or older also received tamoxifen (Nolvadex).

About half the patients in each treatment arm were age 49 or younger at enrollment, and a quarter were ages 50 to 59. Roughly three fourths of the patients were node negative, and 25% to 30% had tumors smaller than 2 cm; 13% had tumors larger than 5 cm.

"The primary purpose of the study was to determine if preoperative chemotherapy, as opposed to postoperative chemotherapy, will be more effective in terms of disease-free survival and overall survival in patients who have operable breast cancer," Dr. Mamounas said.

Secondary aims related to clinical and pathological responses to preoperative chemotherapy and to the ability of preoperative therapy to downstage axillary nodes and increase lumpectomy rates. The investigators also wanted to see whether tumor response to preopera-tive chemotherapy correlated with disease-free or overall survival.

At a mean follow-up of six years, patients in each treatment arm had a 67% disease-free survival rate and 80% overall survival rate, Dr. Mamounas said.

Nodal Downstaging

Preoperative chemotherapy did result in nodal downstaging, as 60% of patients had negative nodes at surgery versus 42% of patients who had conventional adjuvant chemotherapy. Preoperative therapy also was associated with a higher rate of lumpectomy, 68% versus 60%.

Notably, 249 patients given preopera-tive chemotherapy had complete clinical remissions prior to surgery. In 63 of these patients, no evidence of tumor could be found on histologic examination of specimens. Another 26 patients had only ductal carcinoma in situ (DCIS).

Evaluation of disease-free survival by initial response to preoperative chemotherapy revealed a correlation. Disease-free survival exceeded 80% in the 89 patients who had complete remissions or residual DCIS, but was about 70% or less in patients who had responses other than complete response or DCIS after preoper-ative chemotherapy. A similar pattern emerged for overall survival. The two treatment arms did not differ with respect to site of first recurrence.

"In patients with operable breast cancer, preoperative chemotherapy is safe and results in high rates of clinical tumor response and increased rates of breast preservation," Dr. Mamounas said. "When compared to postoperative chemotherapy, preoperative treatment results in equivalent disease-free survival, distant disease-free survival, and overall survival."

On the basis of these results, he continued, "preoperative chemotherapy may be considered an alternative to standard adjuvant chemotherapy in patients who are candidates for chemotherapy."

Dr. Mamounas said that the results have led NSABP investigators to launch another clinical trial to explore the effects of preoperative chemotherapy. The trial will randomize patients to the doxorubicin-cyclophosphamide combination, followed by surgery or followed by preoperative or postoperative administration of docetaxel (Taxotere).

"Preoperative chemotherapy results in equivalent overall and disease-free survival, and provides additional information that can be useful to guide further systemic and local intervention," he said. "We plan to pursue this finding in the upcoming trial."

The purpose of the new trial, he said, is to see whether the addition of a taxane will prolong disease-free survival and overall survival, and increase clinical and pathological response rates, rates of axillary node downstaging, and breast preservation.

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