Cell proliferation and outcome following doxorubicin plus CMF regimens in node-positive breast cancer

Rosella Silvestrini, Antonella Luisi, Milvia Zambetti, Sonia Cipriani, Pinuccia Valagussa, Gianni Bonadonna, Maria Grazia Daidone

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At the Istituto Nazionale Tumori of Milan, a randomised adjuvant chemotherapy trial was carried out from 1982 to 1990 to compare alternating with sequential regimens of doxorubicin and CMF in 403 patients with more than 3 positive axillary nodes. Tumour proliferative activity was determined in 71% (285 cases) of women entering the clinical study. We investigated the relation between proliferative rate, determined as the [3H]thymidine labelling index (TLI) on tumour specimens obtained at diagnostic surgery, and clinical outcome following the 2 regimens, in which the same drugs were administered at the same dose intensity but with a different schedule. A high TLI was significantly associated with 12-year overall relapse (P = 0.009), distant metastasis (P = 0.001), and death (P = 0.002), even in the presence of information provided by tumour size, lymph node involvement, oestrogen receptors, and treatment regimen. The highest relapse-free survival (RFS) probability (45%, 95% CI 34-55%) was observed for patients with tumour TLI <5% and subjected to the sequential treatment. The lowest RFS probability (11%, 95% CI 0-26%) was observed for patients with tumour TLI >9% following the alternating regimen. Intermediate RFS probabilities, ranging from 23% to 34%, were observed for the other kinetic subgroups following the 2 treatment regimens. The benefit of sequential administration of doxorubicin and CMF was evident mainly in patients with tumours at low to intermediate proliferation. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)405-411
Number of pages7
JournalInternational Journal of Cancer
Issue number3
Publication statusPublished - Aug 1 2000

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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