Immunohistochemical phenotype of breast cancer during 25-year follow-up of the Royal Marsden Tamoxifen Prevention Trial

Background The randomized double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. 2471 eligible participants were randomly assigned to tamoxifen (20mg/day) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of ER-positive invasive breast cancer mostly in the post treatment period. Biomarker analysis in this population may identify any sub-group specific preventive effects tamoxifen. Methods After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, PgR, Ki67, HER2 and EGFR were immunohistochemically analysed. Results A 32% reduction in ER+ and PgR+ invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER (p=0.001). These lower ER levels were restricted to the post-treatment period (p=0.018). Amongst the ER+ group there was a similar proportional decrease in PgR+ and PgR- tumours by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2 positive and EGFR positive cancers were higher in the tamoxifen arm but not significantly so. Conclusions Tamoxifen's preventive effects result in reduced ER-positive but not ER-negative tumours and reduced ER expression in the ER-positive cases largely confined to the post-treatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2 and EGFR was modest.

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