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Heublein, Sabine; Mayr, Doris; Meindl, Alfons; Kircher, Alexandra; Jeschke, Udo; Ditsch, Nina (2017): Vitamin D receptor, Retinoid X receptor and peroxisome proliferator-activated receptor gamma are overexpressed in BRCA1 mutated breast cancer and predict prognosis. In: Journal of Experimental & Clinical Cancer Research 36:57
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Abstract

Background: BRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i. e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation. Vitamin D Receptor (VDR), Retinoid X Receptor (RXR) and Peroxisome Proliferator-activated Receptor gamma (PPAR gamma) are known to interact with TRs by forming functional heterodimers. Whether VDR, RXR or PPAR gamma are expressed in BRCA1 mutated breast cancer or may even be present in case of triple negativity is not known. Hence the current study aimed to investigate VDR, RXR and PPAR gamma in BRCA1mut breast cancer and to test whether any of the three may be associated with clinico-pathological criteria including overall survival. Methods: This study analyzed VDR, RXR and PPAR gamma by immunohistochemistry in BRCA1 associated (n = 38) and sporadic breast cancer (n = 79). Receptors were quantified by applying an established scoring system (IR-score) and were tested for association with clinico-pathological variables. Results: VDR, RXR and PPAR. were detected in over 90% of triple negative BRCA1(mut) breast cancer and were significantly (VDR: p < 0.001, RXR: p = 0.010, PPAR gamma: p < 0.001) overexpressed in BRCA1 mutated as compared to sporadic cancer cases. VDR and RXR positivity predicted prolonged overall survival only in BRCA1 mutated cases while such association was not observed in sporadic breast cancer. Conclusions: In conclusion, this is the first study to describe VDR, RXR and PPAR gamma in BRCA1 mutated breast cancer. Based on the data presented here these receptors may be hypothesized to potentially evolve as interesting markers or even targets in hereditary breast cancer. However, independent studies are indispensable thus to confirm this hypothesis.