Prognostic and predictive value of ERβ1 and ERβ2 in the Intergroup Exemestane Study (IES)—first results from PathIES

Abstract

In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ERβ1 expression but not in those with high ERβ1 expression. This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor when compared with tamoxifen and an independent validation is warranted.

High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy–Treated Patients—Results from a Population-Based Breast Cancer Cohort

“…As with all observational studies, the current study has built-in limitations, such as changes in treatment regimens over time and differences in the selection of treatment and how they are combined. This may account for the null finding on endocrine treatment and also limits the possibilities of comparing our result with previous randomized controlled trials, such as the study by Speirs and colleagues (15). Although Speirs and colleagues reported ERb1 to be prognostic among patients who received switch treatment, they did not detect a prognostic benefit of ERb1 expression in their overall population, in which all women received endocrine treatment.…”

“…Therein, ERb1 was not prognostic among all endocrine-treated patients. However, the patients with ERa þ breast tumors with low, but not with high, ERb1 expression had a survival benefit from the switch from tamoxifen to exemestane (15). Furthermore, Wang and colleagues showed that high tumor ERb1 expression was an independent prognostic marker for DFS and OS in a large retrospective series of triple-negative breast cancer (TNBC) patients and proposed specific ERb agonists as a potential addition to chemotherapy for these patients (16).…”

Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)—PathIES

“…The study design, detailed eligibility criteria and treatment schedules have been previously described [ 2 ]. IES was a multicentre, international, randomised, double-blind phase III study, comparing exemestane 25 mg/day to tamoxifen 20 mg/day (30 mg in Denmark) prescribed for 2–3 years in postmenopausal women with ER+/unknown primary breast cancer who remained disease free after receiving adjuvant tamoxifen therapy for 2 to 3 years [ 4 ]. The IES study recruited in total 4724 postmenopausal women from 37 countries (366 centres) between 1998 and 2003 [ 4 ].…”

“…Currently, it remains elusive whether suitable biomarkers can be identified that would facilitate optimal endocrine treatment selection in the adjuvant treatment of breast cancer, identifying individual patients who would derive selective benefit from tamoxifen, AIs or sequential treatment. Our previous analyses showed that high expression of ERß is indicative of no benefit in switching [ 4 ]. In contrast, high levels of cell proliferation marker Ki67 indicated selective benefit of AIs over tamoxifen alone [ 5 ].…”

Predictive markers of endocrine response in breast cancer

“…The role of ER-beta appears complex and dependent on whether ER-alpha is present leading to a bi-faceted role[8], however several clinical studies have suggested predictive effects for specific ER-beta isoforms[8,9]. Low expression of the membrane-bound GPER1 is associated with favourable outcome to tamoxifen[10] while high expression has been associated with tamoxifen resistance[11].…”