Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. II. DNA flow cytometry changes during chemotherapy, tumor regression, and short-term follow-up

Abstract

Between May 1986 and May 1987, 35 primary noninflammatory breast carcinomas (T3N0-N1M0) were studied by means of DNA flow cytometry (FCM-DNA) before and after each of three courses of preoperative chemotherapy (doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil) to assess initial nuclear DNA content, initial S-phase fraction (SPF), and the impact of chemotherapy on these parameters. Correlations were sought with objective regression and short-term follow-up. Four sequential cytopunctures were performed for cytologic examination and FCM-DNA analyses. Ten tumors were diploid and 25 aneuploid. No significant changes in FCM-DNA parameters during chemotherapy were observed in diploid tumors, and no regression was seen in nine of the ten cases. Among the 25 aneuploid tumors, 10 showed changes in DNA content and/or kinetic parameters. A significant correlation was observed between objective regression and initial FCM-DNA content (P = 0.008), initial SPF (P = 0.004), and changes in FCM-DNA patterns observed during chemotherapy (P = 0.00005). During the follow-up period (range, 27 to 41 months), 13 patients had relapses. Patients with aneuploid tumors were more likely to have relapses (n = 11) than patients with diploid tumors (n = 2), and patients with high SPF were more likely to have relapses than patients with low SPF, but the differences were not significant. Similarly, changes in FCM-DNA parameters were observed more often in patients who had relapses, but, again, the difference was not significant. In 5 of the 13 patients who had relapses, FCM-DNA analyses were performed on cytopunctures of the recurrences: patterns were identical to those observed before treatment even when the primary tumor regressed or showed changes in FCM-DNA parameters during chemotherapy.