The importance of temporal effects in evaluating the prognostic impact of joint ERPR expression in premenopausal women with node-positive breast cancer

Although there is abundant information about the independent effects of estrogen receptor (ER) and progesterone receptor (PR) on outcomes of breast cancer, comparatively little is known about the impact of joint (ER+PR+, ER+PR−, ER−PR+ and ER−PR−) ERPR expression. The purpose of this study was to evaluate the prognostic relevance of joint ERPR expression to progression free survival (PFS). Data from 710 patients with a median follow-up of 119 months has been analyzed retrospectively. Our results indicate that the effect of the ER+PR+ phenotype on PFS was significantly time-dependent (p < 0.0001); favorable in the first 3 years of follow-up (HR = 0.67, p = 0.0175) compared to ER−PR− phenotype, but unfavorable during the later follow-up period (HR =  2.89, p = 0.0006). Similar patterns were also observed for ER+PR− and ER−PR+ phenotypes, but the effect did not reach statistical significance. In the tree-based analysis, we found that, among patients with more than 4 positive nodes and age greater than 40, those with ER−PR+ tumors had the worst PFS ( p = 0.025), and among patients with 1–3 positive nodes and stage of T1 and T2, those with ER+PR− had the worst outcome ( p = 0.006). Our results demonstrate that failure to recognize the time-varying effect of the steroid hormonal receptors can obscure their role in the prognosis of breast cancer. We also provide more evidence to support the concept that ER−PR+ is a real group representing a distinct clinical entity.