Tamoxifen in early-stage estrogen receptor-positive breast cancer: overview of clinical use and molecular biomarkers for patient selection

Abstract

Tamoxifen was the first targeted anticancer agent for breast cancer patients and its effects on reduction of breast cancer events and improvement in overall survival are undisputed. Hence, it has long been considered an essential part of patient care. Recent results of several large adjuvant hormonal trials evaluating the use of aromatase inhibitors in comparison with the previous standard of five years of tamoxifen has led to a paradigm shift, ensuring the inclusion of an aromatase inhibitor as part of standard endocrine therapy for most postmenopausal women diagnosed today with estrogen receptor-positive breast cancer. However, one could argue that despite statistically significant improvements in breast cancer events, an overall survival advantage has not been clear. In this review, we discuss recent genomic and molecular data pertaining to estrogen receptor-positive breast cancer and how this knowledge may aid clinicians to prescribe adjuvant hormonal treatment in the future. A combination of gene expression and genetic aberration markers may be most useful in discerning a population that is still appropriate for adjuvant tamoxifen treatment.

Keywords: PI3K; aromatase inhibitors; endocrine therapy; mutation; prediction; resistance; tamoxifen.

Figure 1

Kaplan–Meier graphs of different clinical outcomes of ER-positive breast cancer patients treated with adjuvant tamoxifen monotherapy. Patient series is described in reference . Previously the gene expression grade index (GGI) was used as a measure of proliferation activity to divide ER-positive breast cancer into luminal A and B phenotypes A). Further limited knowledge of important DNA aberrations has identified PIK3CA and AKT1 mutant breast cancers with a similar survival as the luminal A subgroup and HER2 and FGFR1 amplified breast cancers as the luminal B group. Hence, FGFR1 represents a candidate molecular target for some luminal B tumors B). It is likely that both gene expression and molecular aberration may define a group of women suitable for tamoxifen monotherapy in the future.