FLOW CYTOMETRIC DNA-PLOIDY DEFINES PATIENTS WITH POOR-PROGNOSIS IN NODE-NEGATIVE BREAST-CANCER

Flow cytometric DNA analysis was performed on fine-needle aspirates fr om frozen tumour biopsies from 421 node-negative, non-adjuvantly-treat ed breast-cancer patients with a median observation time of 6.75 years . Among premenopausal patients (n = 175), those having at leas one DNA ''hypoploid'' sub-population defined as DNA index (DI) <0.96 or 1.44 less than or equal to DI < 1.92 (n = 81) were characterized by early r ecurrences (log-rank p = 0.05, Wilcoxon p = 0.007), poor overall survi val (OS) (p < 0.001) and poor survival after recurrence (p < 0.001). I n the postmenopausal group (n = 246), there were no significant differ ences among 7 different DI classes regarding either recurrence-free su rvival (RFS) or OS. S-phase fraction (SPF), divided into quartiles, pr edicted OS in premenopausal patients only (p = 0.02). Conventional mul tivariate Cox analysis of OS in the premenopausal group revealed hypop loidy to be the only independent prognostic factor involving a relativ e risk (RR) of 22.8. Age less than or equal to 40 years was of margina l significance, whereas SPF, histological grade (WHO), oestrogen and p rogesterone receptor (PgR) content, tumour size and number of lymph no des removed were excluded from the model. Application of the conventio nal Cox model to the premenopausal group regarding RFS was found inapp ropriate due to lack of proportionality of the hazards of hypoploidy, SPF and histological grade. However, introduction of time-dependent co -variates using 2 years as cut-off level showed hypoploidy with a RR o f 3.52 and age less than or equal to 40 years with a RR of 3.28 to be independent prognostic factors. In the postmenopausal group, the conve ntional Cox model identified the number of lymph nodes removed to be t he only independent prognostic factor regarding RFS as well as OS, whe reas SPF <9% (lowest quartile) was of marginal significance in RFS ana lysis. Hypoploidy was correlated to high SPF, low PGR content of low d ifferentiation, indicating that hypoploid tumours proliferate rapidly and hormone-independently. These patients may therefore benefit from a djuvant chemotherapy administered while tumour burden and risk of drug resistance are still low. (C) 1994 Wiley-Liss, Inc.