Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ERβ and Mutant p53

Abstract

The absence of effective therapeutic targets and aggressive nature of triple-negative breast cancer (TNBC) renders this disease subset difficult to treat. Although estrogen receptor beta (ERβ) is expressed in TNBC, studies on its functional role have yielded inconsistent results. However, recently, our preclinical studies, along with other observations, have shown the potential therapeutic utility of ERβ in the context of mutant p53 expression. The current case study examines the efficacy of the selective estrogen receptor modulator tamoxifen in p53-mutant TNBC with brain metastases. Significant increase in ERβ protein expression and anti-proliferative interaction between mutant p53 and ERβ were observed after cessation of tamoxifen therapy, with significant regression of brain metastases. This case study provides supporting evidence for the use of tamoxifen in p53-mutant, ERβ+TNBC, especially in the setting of brain metastasis.

The Potential of Hormonal Therapies for Treatment of Triple-Negative Breast Cancer

“…Although not traditionally used for ERα-negative tumors, preclinical and clinical research has shown that ERβ can influence the effectiveness of tamoxifen in a small percentage of TNBC patients. In a 2023 case study, the use of tamoxifen in an ERβ-positive / p53-mutant TNBC patient who had experienced brain metastases was evaluated [36]. Treatment with tamoxifen led to a significant reduction in tumor volume of the brain metastases.…”

Divergent features of ERβ isoforms in triple negative breast cancer: progress and implications for further research

“…ERβ1 has been shown to downregulate p53. In p53-mutated breast cancer, ERβ1 inhibits the proliferative and migratory activity of TNBC cells by suppressing the oncogenic function of mutant p53 ( Bado et al, 2016 ), an effect that may be further enhanced by tamoxifen treatment ( Scarpetti et al, 2023 ). However, ERβ has been reported to enhance proliferation in a wild type p53 cell line ( Mukhopadhyay et al, 2019 ).…”

Bipyraloxifene – a modified raloxifene vector against triple-negative breast cancer

“…7 Delving deeper into understanding of the role of the endocrine system in the development of TNBC tumours created the possibility to re-evaluate SERMs for treatment of this subtype of breast cancer. 8,9 For instance, it was shown that a specific isoform of ERα (e.g. ERα36) mediates the oestrogen signalling pathway participating in specific transcriptomic signatures of TNBC.…”