Regular Article

British Journal of Cancer (2001) 85, 1106–1112. doi:10.1054/bjoc.2001.2048 www.bjcancer.com
Published online 16 October 2001

Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer

A Bottini1, A Berruti3, A Bersiga2, M P Brizzi3, P Bruzzi4, S Aguggini1, A Brunelli1, G Bolsi2, G Allevi1, D Generali1, E Betri2, G Bertoli2, P Alquati1 and L Dogliotti3

  1. 1Centro di Senologia, Viale Concordia 1, 26100 Cremona
  2. 2Servizio di Anatomia Patologica, Azienda Ospedaliera Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona
  3. 3Oncologia Medica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi, Regione Gonzole 10, 10043 Orbassano, Torino
  4. 4Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genova, Italy

Received 6 December 2000; Revised 9 July 2001; Accepted 13 July 2001.

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Abstract

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

Ki67, epirubicin, CMF, tamoxifen

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