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

Abstract

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

• biomarkers
• breast cancer
• estrogen receptor
• progesterone receptor
• receptor conversion
• Tamoxifen