Abstract
The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (n = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. 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, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. 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 posttreatment period (P = 0.018). Among the ER+ group, there was a similar proportional decrease in PgR+ and PgR- tumors 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. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. Cancer Prev Res; 10(3); 171-6. ©2017 AACR.
Highlights
In vivo laboratory evidence that the incidence of breast cancer could be reduced and an observed reduction in the risk of new contralateral breast cancer resulting from adjuvant treatment of women with primary breast cancer with the selective estrogen receptor modulator (SERM), tamoxifen [1, 2], indicated that this drug could be used to prevent breast cancer in healthy women
We previously reported that in 67 tumors from the Royal Marsden Prevention Trial (RMPT) (35 placebo, 32 tamoxifen arm), median ER levels were lower in the tumors developing in tamoxifen-treated patients [6]
The primary objective of the current study was to determine whether randomization to possible risk reduction treatment with tamoxifen or placebo was associated with differences in the commonly measured phenotypic markers ER, progesterone receptor (PgR), HER2, and Ki67 as well as EGFR
Summary
In vivo laboratory evidence that the incidence of breast cancer could be reduced and an observed reduction in the risk of new contralateral breast cancer resulting from adjuvant treatment of women with primary breast cancer with the selective estrogen receptor modulator (SERM), tamoxifen [1, 2], indicated that this drug could be used to prevent breast cancer in healthy women. Together with the RMPT, these recruited a total of more than 25,000 healthy women at increased risk of breast cancer. Overview of these trials confirmed a significant reduction in the risk of developing breast. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).
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