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Ann Oncol. 2012 Dec;23(12):2997-3006. doi: 10.1093/annonc/mds586. Epub 2019 Dec 4.

Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement.

Author information

1
Department of Medical Oncology, Georges-François Leclerc Cancer Center, Dijon, France.
2
Department of Biostatistics and Epidemiology, Jules Bordet Institute, Brussels, Belgium.
3
Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France. Electronic address: fandre@igr.fr.
4
Department of Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
5
Institute of Pathology, Charité University Medicine, Berlin, Germany.
6
Medical Oncology Unit, Hospital of Prato, Istituto Toscani Tumori, Prato, Italy.
7
Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
8
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
9
Centre des Tumeurs, Jules Bordet Institute, Brussels, Belgium.
10
Institute of Cancer Research, Royal Marsden Foundation Trust, London, UK.
11
Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands.
12
European Institute of Oncology, University of Milan, Milan, Italy.
13
Department of Translational Research, Jules Bordet Institute, Brussels, Belgium.
14
Breakthrough Breast Cancer Research, Institute of Cancer Research, London, UK.

Abstract

The 2012 IMPAKT task force investigated the medical usefulness of current methods for the classification of breast cancer into the 'intrinsic' molecular subtypes (luminal A, luminal B, basal-like and HER2). A panel of breast cancer and/or gene expression profiling experts evaluated the analytical validity, clinical validity and clinical utility of two approaches for molecular subtyping of breast cancer: the prediction analysis of microarray (PAM)50 assay and an immuno-histochemical (IHC) surrogate panel including oestrogen receptor (ER), HER2 and Ki67. The panel found the currently available evidence on the analytical validity and clinical utility of Ki67 based on a 14% cut-off and PAM50 to be inadequate. The majority of the working group members found the available evidence on the analytical validity, clinical validity and clinical utility of ER/HER2 to be convincing. The panel concluded that breast cancer classification into molecular subtypes based on the IHC assessment of ER, HER2 and Ki67 with a 14% cut-off and on the PAM50 test does not provide sufficiently robust information to modify systemic treatment decisions, and recommended the use IHC for ER and HER2 for the identification of clinically relevant subtypes of breast cancers. Methods for breast cancer classification into molecular subtypes should, however, be incorporated into clinical trial design.

KEYWORDS:

Ki-67; PAM50; breast cancer; molecular classification; molecular subclasses

PMID:
32018802
DOI:
10.1093/annonc/mds586

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