Momoko Akashi1,2, Rin Yamaguchi3,4, Hironori Kusano1, Sachiko Ogasawara1, Eiji Abe5, Hitoshi Obara6, Miki Yamaguchi7, Jun Akiba8, Tatsuyuki Kakuma6, Maki Tanaka7, Yoshito Akagi2, Hirohisa Yano1. 1. Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. 2. Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan. 3. Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. rin@med.kurume-u.ac.jp. 4. Department of Pathology and Laboratory Medicine, Kurume University Medical Center, 155-1 Kokubu, Kurume, Fukuoka, 859-0863, Japan. rin@med.kurume-u.ac.jp. 5. Department of Pathology and Laboratory Medicine, Kurume University Medical Center, 155-1 Kokubu, Kurume, Fukuoka, 859-0863, Japan. 6. Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka, Japan. 7. Department of Surgery, Japan Community Healthcare Organization Kurume General Hospital, Kurume, Fukuoka, Japan. 8. Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.
Abstract
PURPOSE: Although HER2-positive (HER2+) invasive breast carcinomas (BC) have a different clinical therapeutic responsiveness according to estrogen and progesterone receptor expression, the relationship with androgen receptors (AR), which are the same family of steroid hormones, is poorly understood. We investigated the relationship between AR expression in HER2 BCs and therapeutic responsiveness and prognosis in this study. METHODS: We evaluated patients with HER2 (H) + invasive BC undergoing surgery after neoadjuvant chemotherapy (± HER2-targeted therapies) from 2007-2017, classified as hormone receptor-positive (Allred score: 2-8) (luminal B: LH) and receptor-negative groups (Allred: score 0) (non-luminal: NLH). AR expression was assessed by immunostaining pre-neoadjuvant chemotherapy biopsy specimens, positive with Allred score ≥ 4. The pathological complete response, disease-free survival, and overall survival rates were compared between AR-positive and AR-negative groups. RESULTS: We classified 82 patients with HER2 + invasive BC into LH (n = 45, 54.9%) and NLH groups (n = 37, 45.1%), and AR + was observed in 43 patients (52.4%) (LH: 23, 51.1%; NLH: 20, 54.1%; p = 0.79). Quasi-pathological complete response was observed in 40 patients (48.8%) (LH: 18, 40%; NLH: 22, 59.5%; p = 0.08) overall, and in 31 AR + patients (72.1%) (LH: 15, 34.9%; NLH: 16, 37.2%), significantly higher than in the AR - group for both subgroups (p < 0.001). Regarding prognosis, disease-free survival was relatively better in the AR + group in all HER2 + BCs (p = 0.085), and overall survival was significantly better in the AR + group for NLH (p = 0.029). CONCLUSIONS: High AR expression may be a useful predictor of therapeutic effects and prognosis in both subgroups of HER2 + BCs.
PURPOSE: Although HER2-positive (HER2+) invasive breast carcinomas (BC) have a different clinical therapeutic responsiveness according to estrogen and progesterone receptor expression, the relationship with androgen receptors (AR), which are the same family of steroid hormones, is poorly understood. We investigated the relationship between AR expression in HER2 BCs and therapeutic responsiveness and prognosis in this study. METHODS: We evaluated patients with HER2 (H) + invasive BC undergoing surgery after neoadjuvant chemotherapy (± HER2-targeted therapies) from 2007-2017, classified as hormone receptor-positive (Allred score: 2-8) (luminal B: LH) and receptor-negative groups (Allred: score 0) (non-luminal: NLH). AR expression was assessed by immunostaining pre-neoadjuvant chemotherapy biopsy specimens, positive with Allred score ≥ 4. The pathological complete response, disease-free survival, and overall survival rates were compared between AR-positive and AR-negative groups. RESULTS: We classified 82 patients with HER2 + invasive BC into LH (n = 45, 54.9%) and NLH groups (n = 37, 45.1%), and AR + was observed in 43 patients (52.4%) (LH: 23, 51.1%; NLH: 20, 54.1%; p = 0.79). Quasi-pathological complete response was observed in 40 patients (48.8%) (LH: 18, 40%; NLH: 22, 59.5%; p = 0.08) overall, and in 31 AR + patients (72.1%) (LH: 15, 34.9%; NLH: 16, 37.2%), significantly higher than in the AR - group for both subgroups (p < 0.001). Regarding prognosis, disease-free survival was relatively better in the AR + group in all HER2 + BCs (p = 0.085), and overall survival was significantly better in the AR + group for NLH (p = 0.029). CONCLUSIONS: High AR expression may be a useful predictor of therapeutic effects and prognosis in both subgroups of HER2 + BCs.
Authors: T Sørlie; C M Perou; R Tibshirani; T Aas; S Geisler; H Johnsen; T Hastie; M B Eisen; M van de Rijn; S S Jeffrey; T Thorsen; H Quist; J C Matese; P O Brown; D Botstein; P E Lønning; A L Børresen-Dale Journal: Proc Natl Acad Sci U S A Date: 2001-09-11 Impact factor: 11.205
Authors: M J Ellis; A Coop; B Singh; L Mauriac; A Llombert-Cussac; F Jänicke; W R Miller; D B Evans; M Dugan; C Brady; E Quebe-Fehling; M Borgs Journal: J Clin Oncol Date: 2001-09-15 Impact factor: 44.544
Authors: G Curigliano; H J Burstein; E P Winer; M Gnant; P Dubsky; S Loibl; M Colleoni; M M Regan; M Piccart-Gebhart; H-J Senn; B Thürlimann; F André; J Baselga; J Bergh; H Bonnefoi; S Y Brucker; F Cardoso; L Carey; E Ciruelos; J Cuzick; C Denkert; A Di Leo; B Ejlertsen; P Francis; V Galimberti; J Garber; B Gulluoglu; P Goodwin; N Harbeck; D F Hayes; C-S Huang; J Huober; K Hussein; J Jassem; Z Jiang; P Karlsson; M Morrow; R Orecchia; K C Osborne; O Pagani; A H Partridge; K Pritchard; J Ro; E J T Rutgers; F Sedlmayer; V Semiglazov; Z Shao; I Smith; M Toi; A Tutt; G Viale; T Watanabe; T J Whelan; B Xu Journal: Ann Oncol Date: 2017-08-01 Impact factor: 32.976
Authors: C M Perou; T Sørlie; M B Eisen; M van de Rijn; S S Jeffrey; C A Rees; J R Pollack; D T Ross; H Johnsen; L A Akslen; O Fluge; A Pergamenschikov; C Williams; S X Zhu; P E Lønning; A L Børresen-Dale; P O Brown; D Botstein Journal: Nature Date: 2000-08-17 Impact factor: 49.962
Authors: Antonio Llombart-Cussac; Javier Cortés; Laia Paré; Patricia Galván; Begoña Bermejo; Noelia Martínez; Maria Vidal; Sònia Pernas; Rafael López; Montserrat Muñoz; Paolo Nuciforo; Serafín Morales; Mafalda Oliveira; Lorena de la Peña; Alexandra Peláez; Aleix Prat Journal: Lancet Oncol Date: 2017-02-24 Impact factor: 41.316
Authors: Shaheenah Dawood; Kristine Broglio; Aman U Buzdar; Gabriel N Hortobagyi; Sharon H Giordano Journal: J Clin Oncol Date: 2009-11-23 Impact factor: 44.544
Authors: Therese Sorlie; Robert Tibshirani; Joel Parker; Trevor Hastie; J S Marron; Andrew Nobel; Shibing Deng; Hilde Johnsen; Robert Pesich; Stephanie Geisler; Janos Demeter; Charles M Perou; Per E Lønning; Patrick O Brown; Anne-Lise Børresen-Dale; David Botstein Journal: Proc Natl Acad Sci U S A Date: 2003-06-26 Impact factor: 12.779