Pre-, peri-, and postoperative chemotherapy for breast cancer: is one better than the other?

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a "curative" intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P < 0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P < 0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival.