Fernando A Angarita1,2, Masanori Oshi1,3, Akimitsu Yamada3, Li Yan4, Ryusei Matsuyama3, Stephen B Edge1,5, Itaru Endo3, Kazuaki Takabe6,7,8,9,10. 1. Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 2. Division of Surgical Oncology, Department of Surgery, Houston Methodist Hospital, Houston, TX, USA. 3. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. 4. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 5. Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USA. 6. Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. kazuaki.takabe@roswellpark.org. 7. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. kazuaki.takabe@roswellpark.org. 8. Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USA. kazuaki.takabe@roswellpark.org. 9. Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. kazuaki.takabe@roswellpark.org. 10. Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan. kazuaki.takabe@roswellpark.org.
Abstract
PURPOSE: Sentinel lymph node biopsy is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogeneous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. METHODS: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts. RESULTS: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3-predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease-specific survival among older women. CONCLUSION: Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.
PURPOSE: Sentinel lymph node biopsy is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogeneous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. METHODS: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts. RESULTS: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3-predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease-specific survival among older women. CONCLUSION: Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.
Authors: Carl-Magnus Rudenstam; David Zahrieh; John F Forbes; Diana Crivellari; Stig B Holmberg; Piercarlo Rey; David Dent; Ian Campbell; Jürg Bernhard; Karen N Price; Monica Castiglione-Gertsch; Aron Goldhirsch; Richard D Gelber; Alan S Coates Journal: J Clin Oncol Date: 2005-12-12 Impact factor: 44.544
Authors: Soonmyung Paik; Steven Shak; Gong Tang; Chungyeul Kim; Joffre Baker; Maureen Cronin; Frederick L Baehner; Michael G Walker; Drew Watson; Taesung Park; William Hiller; Edwin R Fisher; D Lawrence Wickerham; John Bryant; Norman Wolmark Journal: N Engl J Med Date: 2004-12-10 Impact factor: 91.245
Authors: Andrew J Gentles; Aaron M Newman; Chih Long Liu; Scott V Bratman; Weiguo Feng; Dongkyoon Kim; Viswam S Nair; Yue Xu; Amanda Khuong; Chuong D Hoang; Maximilian Diehn; Robert B West; Sylvia K Plevritis; Ash A Alizadeh Journal: Nat Med Date: 2015-07-20 Impact factor: 53.440
Authors: Kevin S Hughes; Lauren A Schnaper; Jennifer R Bellon; Constance T Cirrincione; Donald A Berry; Beryl McCormick; Hyman B Muss; Barbara L Smith; Clifford A Hudis; Eric P Winer; William C Wood Journal: J Clin Oncol Date: 2013-05-20 Impact factor: 44.544
Authors: Ethan Cerami; Jianjiong Gao; Ugur Dogrusoz; Benjamin E Gross; Selcuk Onur Sumer; Bülent Arman Aksoy; Anders Jacobsen; Caitlin J Byrne; Michael L Heuer; Erik Larsson; Yevgeniy Antipin; Boris Reva; Arthur P Goldberg; Chris Sander; Nikolaus Schultz Journal: Cancer Discov Date: 2012-05 Impact factor: 39.397
Authors: Jeffrey Landercasper; Lisa Bailey; Tiffany S Berry; Robert R Buras; Amy C Degnim; Oluwadamilola M Fayanju; Joshua Froman; Jennifer Gass; Caprice Greenberg; Starr Koslow Mautner; Helen Krontiras; Roshni Rao; Michelle Sowden; Judy A Tjoe; Barbara Wexelman; Lee Wilke; Steven L Chen Journal: Ann Surg Oncol Date: 2016-06-22 Impact factor: 5.344