Takeo Fujii1,2,3,4, Hiroko Masuda5, Yee Chung Cheng6, Fei Yang7, Aysegul A Sahin8, Yasuto Naoi9, Yuki Matsunaga5, Akshara Raghavendra1, Arup Kumar Sinha1, Jose Rodrigo Espinosa Fernandez1, Anjali James1, Keisuke Yamagishi10, Tomoko Matsushima10, Robert Schuetz4, Debu Tripathy1, Sachiyo Tada10, Rubie S Jackson11, Shinzaburo Noguchi9,12, Seigo Nakamura5, Jared D Acoba3,4, Naoto T Ueno13,14. 1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. 2. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. 3. John A. Burns School of Medicine, University of Hawai'i, 651 Ilalo St, Honolulu, HI, 96813, USA. 4. University of Hawai'i Cancer Center, 701 Ilalo St, Honolulu, HI, 96813, USA. 5. Department of Breast Surgical Oncology, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8666, Japan. 6. Division of Hematology and Oncology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI, 53226, USA. 7. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. 8. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. 9. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka, 565-0871, Japan. 10. Sysmex Corporation, 1-5-1, Wakinohama-kaigandori, Chuo-ku, Kobe, Hyogo, 651-0073, Japan. 11. Anne Arundel Medical Center, Rebecca Fortney Breast Center, 2000 Medical Pkwy, Annapolis, MD, 21401, USA. 12. Hyogo Prefectural Nishinomiya Hospital, 13-9, Rokutanjicho, Nishinomiya, Hyogo, 662-0918, Japan. 13. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. nueno@mdanderson.org. 14. Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. nueno@mdanderson.org.
Abstract
PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.
PURPOSE: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. METHODS:Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. RESULTS: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. CONCLUSIONS: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.
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: Joseph A Sparano; Robert J Gray; Peter M Ravdin; Della F Makower; Kathleen I Pritchard; Kathy S Albain; Daniel F Hayes; Charles E Geyer; Elizabeth C Dees; Matthew P Goetz; John A Olson; Tracy Lively; Sunil S Badve; Thomas J Saphner; Lynne I Wagner; Timothy J Whelan; Matthew J Ellis; Soonmyung Paik; William C Wood; Maccon M Keane; Henry L Gomez Moreno; Pavan S Reddy; Timothy F Goggins; Ingrid A Mayer; Adam M Brufsky; Deborah L Toppmeyer; Virginia G Kaklamani; Jeffrey L Berenberg; Jeffrey Abrams; George W Sledge Journal: N Engl J Med Date: 2019-06-03 Impact factor: 91.245
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Authors: Joseph A Sparano; Robert J Gray; Della F Makower; Kathleen I Pritchard; Kathy S Albain; Daniel F Hayes; Charles E Geyer; Elizabeth C Dees; Edith A Perez; John A Olson; JoAnne Zujewski; Tracy Lively; Sunil S Badve; Thomas J Saphner; Lynne I Wagner; Timothy J Whelan; Matthew J Ellis; Soonmyung Paik; William C Wood; Peter Ravdin; Maccon M Keane; Henry L Gomez Moreno; Pavan S Reddy; Timothy F Goggins; Ingrid A Mayer; Adam M Brufsky; Deborah L Toppmeyer; Virginia G Kaklamani; James N Atkins; Jeffrey L Berenberg; George W Sledge Journal: N Engl J Med Date: 2015-09-27 Impact factor: 91.245
Authors: Joseph A Sparano; Robert J Gray; Della F Makower; Kathleen I Pritchard; Kathy S Albain; Daniel F Hayes; Charles E Geyer; Elizabeth C Dees; Matthew P Goetz; John A Olson; Tracy Lively; Sunil S Badve; Thomas J Saphner; Lynne I Wagner; Timothy J Whelan; Matthew J Ellis; Soonmyung Paik; William C Wood; Peter M Ravdin; Maccon M Keane; Henry L Gomez Moreno; Pavan S Reddy; Timothy F Goggins; Ingrid A Mayer; Adam M Brufsky; Deborah L Toppmeyer; Virginia G Kaklamani; Jeffrey L Berenberg; Jeffrey Abrams; George W Sledge Journal: N Engl J Med Date: 2018-06-03 Impact factor: 91.245
Authors: Joseph A Sparano; Michael R Crager; Gong Tang; Robert J Gray; Salomon M Stemmer; Steven Shak Journal: J Clin Oncol Date: 2020-12-11 Impact factor: 50.717