TY - JOUR
T1 - Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
AU - Bayani, Jane
AU - Poncet, Coralie
AU - Crozier, Cheryl
AU - Neven, Anouk
AU - Piper, Tammy
AU - Cunningham, Carrie
AU - Sobol, Monika
AU - Aebi, Stefan
AU - Benstead, Kim
AU - Bogler, Oliver
AU - Dal Lago, Lissandra
AU - Fraser, Judith
AU - Hilbers, Florentine
AU - Hedenfalk, Ingrid
AU - Korde, Larissa
AU - Linderholm, Barbro
AU - Martens, John
AU - Middleton, Lavinia
AU - Murray, Melissa
AU - Kelly, Catherine
AU - Nilsson, Cecilia
AU - Nowaczyk, Monika
AU - Peeters, Stephanie
AU - Peric, Aleksandra
AU - Porter, Peggy
AU - Schröder, Carolien
AU - Rubio, Isabel T.
AU - Ruddy, Kathryn J.
AU - van Asperen, Christi
AU - Van Den Weyngaert, Danielle
AU - van Deurzen, Carolien
AU - van Leeuwen-Stok, Elise
AU - Vermeij, Joanna
AU - Winer, Eric
AU - Giordano, Sharon H.
AU - Cardoso, Fatima
AU - Bartlett, John M.S.
N1 - Funding Information:
The authors declare the following competing interests, no other competing interests have been declared: Dr. John Bartlett has received consultancies/ honoraria from Insight Genetics, Inc., BioNTech AG, Biotheranostics, Inc., Pfizer, Rna Diagnostics Inc., oncoXchange/MedcomXchange Communications Inc, Onco-Cyte Corporation, NanoString Technologies, Inc., Oncology Education. Research funding from ThermoFisher Scientific, Genoptix, Agendia, NanoString Technologies, Inc., Stratifyer GmbH and Biotheranostics, Inc. Dr. Bartlett has received travel support from Biotheranostics, Inc., NanoString Technologies, Inc. and the Breast Cancer Society of Canada. Dr. Bartlett and Dr. Barbro Linderholm are members of advisory boards for Astra Zeneca, Pfizer, Eli Lilly, Novartis, Merck, and Daiichi Sankyo. Dr. Jane Bayani is a co-applicant on multiple patents including those for breast cancer prognostic signatures.
Funding Information:
The funding source had no role in study design or conduct, data collection, data management, data analysis, data interpretation, or writing of the report. This work has been funded by the Breast Cancer Research Foundation (BCRF) with additional funding provided by the Government of Ontario to the Ontario Institute of Cancer Research (OICR). This work was funded by the Breast Cancer Research Foundation (BCRF), the Susan G. Komen for the Cure Foundation and the Ontario Institute of Cancer Research (OICR). Funding for OICR is provided by the Government of Ontario.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. 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 us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
AB - Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. 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 us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
UR - http://www.scopus.com/inward/record.url?scp=85111629180&partnerID=8YFLogxK
U2 - 10.1038/s41523-021-00301-0
DO - 10.1038/s41523-021-00301-0
M3 - Article
AN - SCOPUS:85111629180
SN - 2374-4677
VL - 7
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 98
ER -