title: Effect of tamoxifen on Ki67 labelling index in human breast tumours and its relationship to oestrogen and progesterone receptor status.
abstract: This study aimed to investigate the effect of tamoxifen on breast tumour levels of oestrogen and progesterone receptor (ER and PR) and proliferation as defined by the Ki67 antibody. A group of primary breast cancer patients was randomised to receive either tamoxifen (n = 59) or placebo (n = 44) treatment in the interval between clinic and surgery (median 21 days). Frozen sections of breast tumour biopsies obtained before and after treatment were stained immunocytochemically to obtain the percentage of nuclei containing ER and PR, and a Ki67 labelling index (LI). Tamoxifen-treated patients had a median Ki67 LI of 5.6% in the first biopsy falling to 3.0% in the second biopsy (P < 0.001 by Wilcoxon's matched pairs test), whereas placebo-treated patients had a median Ki67 LI of 5.4% in the first biopsy and 5.75% in the second (no significant difference). No significant differences were observed when the median %ER or %PR staining before and after treatment were compared. The Ki67 LI tended to increase with increasing histological grade and was greater in tumours that were ER - ve compared to those that were ER + ve (> 5% nuclei stained), median 7.8% and 4.3% respectively (P = 0.011 by Mann-Whitney U-test). However, the decline in tumour Ki67 LI following anti-oestrogen treatment failed to correlate with ER and PR status or to predict recurrence over a short follow-up period. To our knowledge, this is the first time that tamoxifen treatment has been shown to reduce the Ki67 LI in human breast tumours in vivo. These data indicate that staining with the Ki67 antibody may be useful in monitoring response to anti-oestrogen therapy.
authors.affiliation: Clinical Research Dept., Christie Hospital NHS Trust, Withington, Manchester.
authors.forename: R B
authors.initials: RB
authors.lastname: Clarke
authors.forename: I J
authors.initials: IJ
authors.lastname: Laidlaw
authors.forename: L J
authors.initials: LJ
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Howell
authors.forename: E
authors.initials: E
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000187:drug effects; D009687:Nuclear Proteins / Q000032:analysis* / Q000187:drug effects; D011960:Receptors, Estrogen / Q000032:analysis* / Q000187:drug effects; D011980:Receptors, Progesterone / Q000032:analysis* / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen