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, NO-N1, MO) 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.

Evaluation of breast carcinoma chemosensitivity by flow cytometric DNA analysis and computer assisted image analysis

“…To improve our previous results for a better selection of patients, we completed our study on 27 carcinomas, using a cell image processor analysis (SAMBA) with cytologic samples obtained before treatment and after the first cycle, in order to: (1) compare FCM DNA results to those obtained with SAMBA cell image analysis and (2) evaluate chemotherapeutic action on SAMBA morphometric parameters, in particular on textural chromatin parameters.…”

Response to the letter from Remvikos

“…First, I would point out that the authors have omitted to reference previous contributions on the same topic (Spyratos et al, 1987;Remvikos et al, 1988a, Briffod et al, 1989. Second, as a cytometrist, I believe that data file histograms should be presented (rather than redrawn ones) as these usually contain extensive information on the quality of the preparations (baseline, noise, skewed peaks, aggregates).…”

“…It was recently shown that DNA-ploidy and Sphase fraction are significantly related to response to cytotoxic chemotherapy (Briffod et al, 1989;Remvikos et al, 1989 Response to the letter from Dr Remvikos…”

“…With regard to the originality of the article and the possible omission of other work (Spyratos et al, 1987;Remvikos et al, 1988;Briffod et al, 1989), we feel our work is indeed original. Both Spyratos and Remvikos, while commenting on the clinical importance of sequential FNAs for flow cytometric DNA analysis, do not provide any data pertaining to reproducibility and variability of such serial FNAs, although both studies, like our own, do provide data comparing FNAs with surgically excised biopsies.…”

“…Both Spyratos and Remvikos, while commenting on the clinical importance of sequential FNAs for flow cytometric DNA analysis, do not provide any data pertaining to reproducibility and variability of such serial FNAs, although both studies, like our own, do provide data comparing FNAs with surgically excised biopsies. The third study (Briffod et al, 1989) was not in print when our manuscript was accepted for publication, hence its exclusion (along with Remvikos et al, 1989).…”