| Autor: |
Okano M; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. tentekomaikocco@hotmail.com., Oshi M; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. masanori.oshi@roswellpark.org., Butash AL; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. ali.butash@roswellpark.org., Asaoka M; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. mariko.asaoka@roswellpark.org., Katsuta E; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. eriko.katsuta@roswellpark.org., Peng X; Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. xuan.peng@roswellpark.org., Qi Q; Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. qianya.qi@roswellpark.org., Yan L; Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. li.yan@roswellpark.org., Takabe K; Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. kazuaki.takabe@roswellpark.org.; Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY 14203-1121, USA. kazuaki.takabe@roswellpark.org.; Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan. kazuaki.takabe@roswellpark.org.; Department of Surgery, Yokohama City University, Yokohama 236-0004, Japan. kazuaki.takabe@roswellpark.org.; Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan. kazuaki.takabe@roswellpark.org.; Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. kazuaki.takabe@roswellpark.org. |
| Abstrakt: |
Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives ( p < 0.001, p < 0.001, respectively) and it correlated with ER expression ( R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = -2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC ( p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC. |
