The relative importance of proliferation and cell death in breast cancer growth and response to tamoxifen.
Changes in tumour volume depend on the relative balance between cell proliferation and cell loss. However, these processes are not independent, and it remains unclear which is more important in tumour progression and regression. For example, the anti-oestrogen tamoxifen, a mainstay in the therapy of breast cancer, has both antiproliferative and pro-apoptotic actions, and their relative importance in clinical efficacy is unknown. Thus, using a model system based on oestrogen receptor (ER)-positive ZR-75-1 breast cancer xenografts, both increased apoptosis and reduced proliferation have been previously shown to occur within 7 days of tamoxifen therapy (Cameron DA, Ritchie AA, Langdon S, Anderson TJ, Miller WR. Tamoxifen induced apoptosis in ZR-75 breast cancer xenografts antedates tumour regression. Breast Cancer Res Treat 1997, 45, 99--107). In the present study, Gompertzian growth curves have been fitted to individual breast cancer xenografts. This demonstrates that the growth rate of the untreated tumours is directly dependent only on the mitotic rate (P<0.001), whereas tumour response to tamoxifen correlates most strongly (P< 0.001) with the relative balance between apoptosis and mitosis, as evidenced by the apoptotic:mitotic ratio.
Cameron
D A
DA
Edinburgh Breast Research Unit, Department of Oncology, Edinburgh University, Edinburgh, UK. dcameron@srv0.med.ac.uk
Ritchie
A A
AA
Miller
W R
WR
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects*; D008940:Mitotic Index / Q000379:methods; D013629:Tamoxifen / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen