Oestrogen receptor and KI67 status in breast carcinomas following primary chemoendocrine therapy

There has been a paucity of data looking at the effect of chemotherapy on proliferation indices in human breast cancer. We have assessed proliferation index in 155 patients randomised to receive either primary MM (Mitoxantrone, Methotrexate) + Tamoxifen (Tarn) prior to surgery (PMT; n = 73, med age 56 yrs) or surgery followed by adjuvant MM + Tam (ADJ; n = 82, med age 55 yrs). Paraffin embedded sections from the surgical excision specimens of both groups were stained immunohistochemically with the MIB-1 monoclonal antibody to Ki67 and a percentage score of positively staining malignant cells obtained. Oestrogen receptor (ER) status was determined by enzyme immunoassay (EIA). ER was not assessable in 9 pts in the PMT arm. Proliferation was significantly lower in the PMT arm (med MIB-l score 1.7%, range 0–84.5%) compared with the ADJ arm (med MIB-1 score 9.9%, range 0–80%) (P = 0.003). In ER positive tumours MIB-l was significantly lower in the PMT arm (1.2%) than the ADJ arm (9.45%) (P < 0.0001). In ER negative tumours there was no significant difference between the PMT (12.3%) and ADJ (16.1%) arms (P = 0.25). These differences indicate that proliferation is reduced following chemo-hormonal therapy but that the effect is largely confined to ER positive tumours. Although the cross sectional nature of the study precludes firm conclusions these data suggest the possibility that in ER negative tumours chemotherapy induced response may be mediated by other processes such as apoptosis. We are currently testing this hypothesis in a prospective longitudinal study. There has been a paucity of data looking at the effect of chemotherapy on proliferation indices in human breast cancer. We have assessed proliferation index in 155 patients randomised to receive either primary MM (Mitoxantrone, Methotrexate) + Tamoxifen (Tarn) prior to surgery (PMT; n = 73, med age 56 yrs) or surgery followed by adjuvant MM + Tam (ADJ; n = 82, med age 55 yrs). Paraffin embedded sections from the surgical excision specimens of both groups were stained immunohistochemically with the MIB-1 monoclonal antibody to Ki67 and a percentage score of positively staining malignant cells obtained. Oestrogen receptor (ER) status was determined by enzyme immunoassay (EIA). ER was not assessable in 9 pts in the PMT arm. Proliferation was significantly lower in the PMT arm (med MIB-l score 1.7%, range 0–84.5%) compared with the ADJ arm (med MIB-1 score 9.9%, range 0–80%) (P = 0.003). In ER positive tumours MIB-l was significantly lower in the PMT arm (1.2%) than the ADJ arm (9.45%) (P < 0.0001). In ER negative tumours there was no significant difference between the PMT (12.3%) and ADJ (16.1%) arms (P = 0.25). These differences indicate that proliferation is reduced following chemo-hormonal therapy but that the effect is largely confined to ER positive tumours. Although the cross sectional nature of the study precludes firm conclusions these data suggest the possibility that in ER negative tumours chemotherapy induced response may be mediated by other processes such as apoptosis. We are currently testing this hypothesis in a prospective longitudinal study.