title: Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer.
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.
authors.affiliation: Centro di Senologia, Azienda Ospedaliera Istituti Ospitalieri, Viale Concordia 1, Cremona, 26100, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bottini
authors.forename: A
authors.initials: A
authors.lastname: Berruti
authors.forename: A
authors.initials: A
authors.lastname: Bersiga
authors.forename: M P
authors.initials: MP
authors.lastname: Brizzi
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: S
authors.initials: S
authors.lastname: Aguggini
authors.forename: A
authors.initials: A
authors.lastname: Brunelli
authors.forename: G
authors.initials: G
authors.lastname: Bolsi
authors.forename: G
authors.initials: G
authors.lastname: Allevi
authors.forename: D
authors.initials: D
authors.lastname: Generali
authors.forename: E
authors.initials: E
authors.lastname: Betri
authors.forename: G
authors.initials: G
authors.lastname: Bertoli
authors.forename: P
authors.initials: P
authors.lastname: Alquati
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53