Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. Cytomorphologic changes, initial tumor ploidy, and tumor regression

Abstract

Thirty-five patients with large but operable breast carcinoma (T3, N0-N1, M0) received before surgery three cycles of preoperative Adriamycin (doxorubicin), vincristine, cyclophosphamide, methotrexate, 5-fluorouracil (AVCMF) chemotherapy (CT). All patients had sequential cytopunctures for both cytologic examination and flow cytometric DNA analysis (FCM): one before treatment and the three others after each cycle of CT. At cytologic examination, 20 carcinomas showed CT-induced cytomorphologic changes. These changes in malignant cells were also evaluated on histologic sections after surgery. A significant relationship was found between cytomorphologic changes in cytopunctures and in the corresponding tumor tissue. The lobular carcinomas did not reveal changes either on cytologic or on histologic study. At FCM analysis before treatment, ten carcinomas were diploid and 25 were nondiploid. When initial tumor ploidy was compared to cytomorphologic changes, none of the diploid carcinomas showed changes. An objective tumor regression was observed in 12 of 20 tumors with cytomorphologic changes and in four of 15 tumors without changes on cytologic examination. But, a significant relationship appeared only when cellular changes were evaluated on histologic analysis. When tumor regression was compared to ploidy before treatment, the rate of objective regression was significantly higher in nondiploid tumors (15/25) than in diploid tumors (one of ten). From these findings, initial tumor diploidy could be a predictor of tumor chemoresistance, whereas cytomorphologic changes during chemotherapy could be an indicator of tumor cell chemosensitivity.