ERβ1 Expression May Guide Endocrine Therapy Use for ERα-Positive Breast Cancer Patients

Measuring ERβ1 expression could aid endocrine treatment decision-making for ERα-positive patients

medwireNews: Researchers have identified a subgroup of patients with oestrogen receptor (ER)α-positive breast cancer who might benefit from changing their endocrine therapy to exemestane after 2 or 3 years of tamoxifen .

Patients with low ERβ1 expression in their tumour samples had better disease-free survival (DFS) if they switched treatments than if they continued with tamoxifen, say Charles Coombes, from Imperial College London, in the UK, and co-workers.

“This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor as compared to tamoxifen”, the team writes in the Annals of Oncology.

The researchers examined tumour samples from 1256 participants of the Intergroup Exemestane Study, comparing exemestane versus tamoxifen in postmenopausal patients with ER-positive primary cancer who had remained disease-free after an initial 2 or 3 years of tamoxifen.

In all, 387 patients were classified as having a high immunohistochemistry score for ERβ1 (≥191) and 351 patients had a high score for ERβ2 (≥164).

There was no significant correlation between ERβ1 or ERβ2 status and DFS or overall survival when the whole cohort of patients was assessed.

But multivariate analysis showed that among patients who continued with tamoxifen, high ERβ1 expression was associated with a significant increase in DFS compared with a low ERβ1 status (hazard ratio [HR]=0.38).

And for patients who switched to exemestane, a low ERβ1 status was a significant predictor of better DFS, with a HR of 0.40.

By contrast, there was no significant interaction between survival outcomes and ERβ2 status with regard to switching or continuing endocrine therapies, Charles Coombes et al say.

“This finding may allow better selection of postmenopausal patients to adjuvant endocrine therapies and a safe switch back to tamoxifen in the case of poor [aromatase inhibitor] tolerance”, the researchers conclude.

“However, due to the exploratory nature of this study, prospective validation is required before advising change in practice”, they caution.


Speirs V, Viale G, Mousa K, et al. Prognostic and predictive value of ERβ1 and ERβ2 in the Intergroup Exemestane Study (IES) – first results from PathIES. Ann Oncol 2015; Advance online publication 22 May. doi: 10.1093/annonc/mdv242

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