The rate of estrogen receptor-conversion associated with tumor progression in estrogen receptor-positive breast cancer patients following adjuvant Tamoxifen administration

Abstract

Background: Hormone Receptor (HR)-discordance between primary breast cancer and metastasis is a known biological phenomenon. Discordance studies usually comprise a heterogeneous group of HR-positive and negative patients and allow for the comparison of changes in HR-status from the primary to the recurrent disease. However, in a clinical setting, the rate of estrogen receptor-conversion following endocrine therapy with agents such as Tamoxifen (TAM) in estrogen receptor-positive cancers is of primary interest as opposed to total receptor discordance.

Aim: To investigate the rate of estrogen receptor-conversion associated with tumor progression in estrogen receptor-positive breast cancer patients following adjuvant TAM administration and to compare the results with the meta-analysis data of HR-discordance studies.

Methods and results: A retrospective double-center review of biomarkers in 67 estrogen receptor-positive breast cancer patients who underwent TAM treatment in the adjuvant setting. The estrogen and progesterone receptor-status were compared at the time of diagnosis and following relapse and the Disease-free Survival, mean duration of TAM treatment as well as the operative, radiation, and cytotoxic therapies registered before TAM treatment, were recorded. Initially, all patients were estrogen receptor-positive. The average age at the time of diagnosis was 52.8 ± 12.4 years. After recurrence, only 47 patients (70.1%) were still estrogen receptor-positive with a highly significant loss of estrogen receptor-expression in 29.9% of cases. The mean duration of TAM treatment was 40.7 ± 19.9 months. 45 patients (i.e., 67.2%) progressed during the TAM treatment and the remaining 22 patients (32.8%) developed relapse after the TAM treatment had finished. Initially, there were 82.1% progesterone receptor-positive and 17.9% progesterone receptor-negative, but after relapse the progesterone receptor-positive cases diminished significantly to 53.7%, showing a progesterone receptor-loss of 28.4%.

Conclusion: The rate of estrogen receptor-loss associated with tumor progression following TAM treatment is approximately 30%, which is of clinical relevance in order to evaluate further endocrine efficacy in these patients. This rate of receptor conversion is roughly 6-13% higher compared to the recently published meta-analysis data of discordance studies. This discrepancy could possibly be due to anti-hormonal therapy with TAM accentuating receptor conversion.

Keywords: Tamoxifen; biomarkers; breast cancer; estrogen receptor; progesterone receptor; receptor conversion.