Long-term pattern of disease recurrence among patients with early-stage breast cancer according to estrogen receptor status and use of adjuvant tamoxifen

Recent studies on the pattern of gene expression in estrogen receptor positive and negative tumours have revealed profound differences according to receptor status. However, it remains unclear if these differences reflect phenotypic traits in addition to sensitivity to endocrine therapy. This paper describes the long-term pattern of disease recurrence among ca. 2,600 pre- and post-menopausal patients with primary breast cancer according to estrogen receptor status. The study was based on patients with an operable, invasive breast cancer entered in one of three controlled clinical trials conducted by the Stockholm Breast Cancer Group. We selected those 2,562 patients who had been randomly allocated between adjuvant tamoxifen and no adjuvant systemic therapy. These patients had a known estrogen receptor status. Tamoxifen reduced locoregional (8.8% vs. 12.4%, hazard ratio (HR), 0.66; 95% CI, 0.52-0.83; P = 0.001, distant recurrences (17.2% vs. 20.2%, HR, 0.81; CI, 0.68-0.97; P = 0.018, as well as breast cancer death (18.7% vs. 23.7%, HR, 0.78; CI, 0.67-0.92; P = 0.002). Among patients not allocated to tamoxifen there was no significant differences in term of neither locoregional (12.4% vs. 12.4%, HR, 1; CI, 0.72-1.41; P = 0.98), nor distant metastases (18.5% vs. 20.7%, HR, 1.11;CI, 0.85-1.45; P = 0.46) according to ER status. The pattern of metastases was not different in ER positive comparison with ER negative. The results showed that the mentioned substantial differences in terms of gene expression appeared mainly to be related to endocrine sensitivity and not to metastatic potential. However, a slight advantage during the first five years for the ER positive versus ER negative patients in terms of cumulative incidence of events, suggested that ER negativity in some cases is correlated with an increased tumour growth rate.