Cyclin E and the
retinoblastoma protein (Rb) are both important regulators of the G1 phase in the cell cycle. Overexpression of
cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of
cyclin E and Rb in
breast cancer patients randomised for
tamoxifen (TAM), CMF (
cyclophosphamide, metotrexate,
5-fluorouracil)
chemotherapy and
radiotherapy (RT) and how their expression affects the patients' response to treatment.
Protein expression was assessed with immunohistochemistry. We found overexpression of
cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of
cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high
cyclin E tumours have less benefit from
tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72).
Cyclin E also tended to predict the benefit from
radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.83) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of
cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with
radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).