Abstract
The aim of this study was to assess the prognostic value of the steroid hormone receptor expression, counting the retinoid X receptor (RXR) and thyroid hormone receptors (THRs), on the two different breast cancer (BC) entities: multifocal/multicentric versus unifocal. The overall and disease-free survival were considered as the prognosis determining aspects and analyzed by uni- and multi-variate analysis. Furthermore, histopathological grading and TNM staging (T = tumor size, N = lymph node involvement, M = distant metastasis) were examined in relation to RXR and THRs expression. A retrospective statistical analysis was carried out on survival-related events in a series of 319 sporadic BC patients treated at the Department of Gynecology and Obstetrics at the Ludwig-Maximillian’s University in Munich between 2000 and 2002. The expression of RXR and THRs, including its two major isoforms THRα1 and THRα2, was analyzed by immunohistochemistry and showed to have a significant correlation for both BC entities in regard to survival analysis. Patients with multifocal/multicentric BC were exposed to a significantly worse disease-free survival (DFS) when expressing RXR. Patients with unifocal BC showed a significantly worse DFS when expressing THRα1. In contrast, a statistically significant positive association between THRα2 expression and enhanced DFS in multifocal/multicentric BC was shown. Especially the RXR expression in multifocal/multicentric BC was found to play a remarkably contradictory role for BC prognosis. The findings imply the need for a critical review of possible molecular therapies targeting steroid hormone receptors in BC treatment. Our results strengthen the need to further investigate the behavior of the nuclear receptor family, especially in relation to BC focality.
Highlights
Introduction distributed under the terms andBreast cancer (BC) is the most frequent malignant tumor in women worldwide [1].With 2.1 million incident cases in 2018 [2,3], half a million deaths, and 14.9 million disabilityadjusted life-years [4], breast cancer is considered one of the greatest challenges for experts to control [5]
The Kaplan–Meier curve visualized (Figure 1) and the log rank test calculated with a p value of 0.036 show a significant negative association of the disease-free survival (DFS) in multifocal/multicentric BC patients when expressing the retinoid X receptor (RXR)
The histopathological TNM staging and tumor grading by WHO (p = 0.466) Kruskal–Wallis analysis revealed no statistical difference for RXR expression in multifocal and/or multicentric BC
Summary
Introduction distributed under the terms andBreast cancer (BC) is the most frequent malignant tumor in women worldwide [1].With 2.1 million incident cases in 2018 [2,3], half a million deaths, and 14.9 million disabilityadjusted life-years [4], breast cancer is considered one of the greatest challenges for experts to control [5]. For distinguishing clinical tumor subtypes, the BC focality is recognized as an important prognostic factor. Multicentric BC is understood as two or more separate invasive tumors in more than one quadrant of the same breast [9,10]. To this point, no standard international definition has been implemented for distinguishing multifocal and multicentric BC [11,12]. Unifocal BC is associated with an enhanced prognosis, including a better overall survival (OS) and disease-free survival (DFS), in comparison to multifocal and/or multicentric BC with the same tumor size. The focality is regarded as an important prognosticator for BC [14,15,16]
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