Test of the association between Ki67 index of breast cancer and local relapse after adjuvant hypofractionated radiotherapy

Rodrigues, D., Somaiah, N., Daley, F., Davies, S., Rakha, E., A'Hern, R., Haviland, J.S., Sydenham, M., Owen, J., Reis-Fhilho, J. and Yarnold, J. (2012) Test of the association between Ki67 index of breast cancer and local relapse after adjuvant hypofractionated radiotherapy. Cancer Research, 72 (24), supplement 3, 6-9. (doi:10.1158/0008-5472.SABCS12-P3-06-09).

Abstract

Introduction: there is a strong inverse association between the proliferation indices of early- and late-responding normal tissues and their sensitivity to radiotherapy fraction size. The aim of this study is to test for association between Ki67 index and the fractionation sensitivity of breast cancer. The hypothesis is that tumours with high Ki67 indices are relatively insensitive to fraction size and be over-represented in tumours relapsing after hypofractionated, radiotherapy.

Methods: between 1986 and 2003, the START pilot and START A trials tested 2 test dose levels of a 13-fraction regimen (3.0 or 3.3 Gy & 3.0 or 3.2 Gy fractions, respectively) in 5 weeks against 25 fractions of 2.0 Gy following primary surgery for early breast cancer. Primary tumour blocks of patients with local tumour relapse were collected for immunohistochemistry (IHC) for Ki67 (manual counting in whole sections), HER2, ER & PR (Allred quick scores in tissue sections). Ki67 was assumed to be log normally distributed with a standard deviation of 0.5–0.9. Assuming evaluable blocks for 240 patients, a standardised detectable difference of 0.45 (90%+ power, 5% significance level) corresponded to a detectable difference in geometric means of 5–10%.

Results: from a total of 3646 patients entered into the START pilot and START A trials, 261 local tumour relapses were recorded at a median follow up of 8.4 years (range 0.9–17.5) and 7.2 (range 0.7–11.9) years respectively. Blocks from 213 patients were recovered, of which 176 were evaluable by IHC. There was no significant difference in proliferation between tumours relapsing after conventional and hypofractionated radiotherapy, with mean Ki67 scores of 7.63 (95%CI: 5.06–11.5) and 5.33 (95CI%: 3.86–7.35), respectively. Mean Ki67 scores in 48 primary triple negative tumours (TNT) that relapsed locally were 15.74 (95%CI: 8.53–29.06) after conventional and 7.52 (95%CI: 3.51–16.1) after hypofractionated radiotherapy, but TNT were equally represented (28%) in both groups.

Conclusion: an association between proliferative indices and fractionation sensitivity in breast tumours has not been demonstrated. If confirmed, it suggests that genetic and epigenetic features unrelated to proliferation are sources of inter-tumour variation in fractionation sensitivity

This record has no associated files available for download.

Contributors

Download statistics