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Poster Session Abstracts

Abstract P6-19-01: Evaluation of multiple transcriptomic gene risk signatures in male breast cancer

J Bayani, C Poncet, CQ Yao, C Crozier, N Anouk, T Piper, C Cunningham, M Sobol, S Aebi, K Benstead, O Bogler, L Dal Lago, J Fraser, FH Hilbers, I Hedenfalk, L Korde, B Linderholm, J Martens, L Middleton, M Murray, C Kelly, C Nilsson, M Nowaczyk, S Peeters, A Peric, P Porter, C Schröder, IT Rubio, KJ Ruddy, C van Asperen, D Van Den Weyngaert, C van Deurzen, E van Leeuwen-Stok, J Vermeij, E Winer, PC Boutros, SH Giordano, F Cardoso and JM Bartlett
J Bayani
Ontario Institute for Cancer Research, Toronto, ON, Canada; European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium; University of Edinburgh, Edinburgh, United Kingdom; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; Cheltenham General Hospital, Gloucestershire, United Kingdom; Global Academic Programs, University of Texas MD Anderson Cancer Center, Houston, TX; Jules Bordet Institute, Brussels, Belgium; Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; Breast International Group, Brussels, Belgium; Lund University, Lund, Sweden; University of Washington, Seattle, WA; Sahlgrenska University Hospital, Gothenburg, Sweden; Medical Oncology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; University of Texas MD Anderson Cancer Center, Houston, TX; Memorial Sloan Kettering Cancer Center, New York, NY; All Ireland Cooperative Oncology Research Group (ICORG), Dublin, United Kingdom; Västmanlands Hospital, Västerås, Sweden; Specialist Hospital. St. Wojciech, Gdansk, Poland; UZ Leuven, Leuven, Belgium; Fred Hutchinson Cancer Research Center & University of Washington, Seattle, WA; University Medical Center Groningen, Groningen, Netherlands; Breast Surgical Unit. Hospital Universitario Vall d´Hebron, Barcelona, Spain; Mayo Clinic, Rochester; Leiden University Medical Center, Leiden, Netherlands; ZNA Middelheim, Middelheim, Belgium; Erasmus Medical Center, Rotterdam, Rotterdam, Netherlands; Dutch Breast Cancer Research Group (BOOG), Amsterdam, Netherlands; ZNA Jan Palfijn, Antwerp, Belgium; Dana-Farber Cancer Institute, Boston; University of Toronto, Toronto, ON, Canada; Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
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C Poncet
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CQ Yao
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C Crozier
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N Anouk
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T Piper
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C Cunningham
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M Sobol
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S Aebi
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K Benstead
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O Bogler
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L Dal Lago
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J Fraser
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FH Hilbers
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I Hedenfalk
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L Korde
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B Linderholm
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J Martens
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L Middleton
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M Murray
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C Kelly
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C Nilsson
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M Nowaczyk
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S Peeters
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A Peric
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P Porter
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C Schröder
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IT Rubio
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KJ Ruddy
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C van Asperen
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D Van Den Weyngaert
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C van Deurzen
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E van Leeuwen-Stok
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J Vermeij
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E Winer
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PC Boutros
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SH Giordano
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F Cardoso
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JM Bartlett
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DOI: 10.1158/1538-7445.SABCS18-P6-19-01 Published February 2019
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Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas

Abstract

Introduction: Male breast cancer (MBC) is a rare disease accounting for less than 1% of all breast cancers (BC) and 1% of all cancers in males. The clinical management is largely extrapolated from female BC. Several multigene assays are increasingly used to guide clinical treatment decisions in female BC, however there is little data on the utility of these tests in MBC.

Methods: Here we present the gene expression results of 380 M0, ER+ve, HER2-ve MBCs enrolled in the Part 1 (retrospective joint analysis) International Male Breast Cancer Program of 1483 patients diagnosed between 1990-2010 (Cardoso et al. Annals of Oncology, 2018). Using a custom Nanostring™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDx® and Mammaprint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by Bayani and Yao et al (npjBreast Cancer, 2017). Survival outcomes by risk classification were analyzed using Cox models with time-dependent covariates when the proportional hazard assumption was not met and adjusted for clinical and treatment variables.

Results: Prosigna-like risk scores identified 99 (26.1%) as low-risk, 159 (41.8%) as intermediate-risk, and 122 (32.1%) as high-risk. Using the TAILORx cut-off (25) for OncotypeDx-like risk of recurrence scoring, 158 (41.6%) were identified as low-risk, while 222 (58.4%) were identified as high-risk. MammaPrint-like results identified 175 (46.1%) as low-risk and 205 (53.9%) as high-risk. Overall, patients classified as high-risk had higher grade, more nodal involvement, larger tumors, and more frequently treated with chemotherapy than low-risk patients. Survival analyses demonstrated clear clinical utility for each test, showing patients at high-risk with poor relapse-free survival (RFS) as compared to patients classified as low-risk: Prosigna-like RFS at 3-years (HR=2.20, 95% CI, 1.28-3.80); Oncotype-like RFS at 3-years (HR=1.92, 95% CI, 1.17-3.17); MammaPrint-like RFS (HR=1.51, 95% CI, 1.00-2.27); with similar findings for distant relapse-free survival (DRFS) and overall survival (OS). Across outcomes and all gene signatures, patients with concordant Low/Low risk classification had better prognosis than those with concordant High/High risk classification. PAM50 intrinsic subtyping identified 147 (38.7%) as Luminal A, 57 (15.0%) as Luminal B, 80 (21.1%) as Her2-enriched and 96 (25.3%) as Basal-like; showing overall 34.5% concordance to clinic-pathological subtyping by central pathology (95% CI, 29.7%-39.5%). Comparison between the tests in the MBC cohort and a comparable cohort of female BC from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial processed in the same way will be presented.

Conclusion: Common transcriptomic assays designed to assess residual risk, validated in female BC, provide similar information in male BC patients. Not surprisingly, disagreement between test results at the individual patient level was observed. To our knowledge, this is the largest study of MBC assayed to generate risk scores of the current commercial BC tests to demonstrate their clinical utility and their differences and similarity to female BC.

This work has been funded by the Breast Cancer Research Foundation (BCRF).

Citation Format: Bayani J, Poncet C, Yao CQ, Crozier C, Anouk N, Piper T, Cunningham C, Sobol M, Aebi S, Benstead K, Bogler O, Dal Lago L, Fraser J, Hilbers FH, Hedenfalk I, Korde L, Linderholm B, Martens J, Middleton L, Murray M, Kelly C, Nilsson C, Nowaczyk M, Peeters S, Peric A, Porter P, Schröder C, Rubio IT, Ruddy KJ, van Asperen C, Van Den Weyngaert D, van Deurzen C, van Leeuwen-Stok E, Vermeij J, Winer E, Boutros PC, Giordano SH, Cardoso F, Bartlett JM. Evaluation of multiple transcriptomic gene risk signatures in male breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-01.

  • ©2019 American Association for Cancer Research.
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Cancer Research: 79 (4 Supplement)
February 2019
Volume 79, Issue 4 Supplement
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Abstract P6-19-01: Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
J Bayani, C Poncet, CQ Yao, C Crozier, N Anouk, T Piper, C Cunningham, M Sobol, S Aebi, K Benstead, O Bogler, L Dal Lago, J Fraser, FH Hilbers, I Hedenfalk, L Korde, B Linderholm, J Martens, L Middleton, M Murray, C Kelly, C Nilsson, M Nowaczyk, S Peeters, A Peric, P Porter, C Schröder, IT Rubio, KJ Ruddy, C van Asperen, D Van Den Weyngaert, C van Deurzen, E van Leeuwen-Stok, J Vermeij, E Winer, PC Boutros, SH Giordano, F Cardoso and JM Bartlett
Cancer Res February 15 2019 (79) (4 Supplement) P6-19-01; DOI: 10.1158/1538-7445.SABCS18-P6-19-01

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Abstract P6-19-01: Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
J Bayani, C Poncet, CQ Yao, C Crozier, N Anouk, T Piper, C Cunningham, M Sobol, S Aebi, K Benstead, O Bogler, L Dal Lago, J Fraser, FH Hilbers, I Hedenfalk, L Korde, B Linderholm, J Martens, L Middleton, M Murray, C Kelly, C Nilsson, M Nowaczyk, S Peeters, A Peric, P Porter, C Schröder, IT Rubio, KJ Ruddy, C van Asperen, D Van Den Weyngaert, C van Deurzen, E van Leeuwen-Stok, J Vermeij, E Winer, PC Boutros, SH Giordano, F Cardoso and JM Bartlett
Cancer Res February 15 2019 (79) (4 Supplement) P6-19-01; DOI: 10.1158/1538-7445.SABCS18-P6-19-01
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