Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ER[beta] and Mutant p53

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 (ER[beta]) 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 ER[beta] 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 ER[beta] protein expression and anti- proliferative interaction between mutant p53 and ER[beta] 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, ER[beta]+TNBC, especially in the setting of brain metastasis. Key words: triple-negative breast cancer; tamoxifen; estrogen receptor [beta]; mutant p53; brain metastasis; proximity ligation assay (PLA)