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Updated: Apr 14, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Defining breast cancer intrinsic subtypes by quantitative receptor expression
Maggie C U Cheang1, Miguel Martin1, Torsten O Nielsen1
1Lineberger Comprehensive Cancer Center and Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA; Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, United Kingdom; Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada; Translation Genomics Unit, Vall d´Hebron Institute of Oncology, Barcelona, Spain; British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain; Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Seville, Spain; Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, Coruña, Spain; Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga, Spain; GEICAM, Madrid, Spain; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada; Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah, USA; Department of Medicine, Washington University, St. Louis, Missouri, USA; Department of Oncology, Hospital of Prato, Istituto Toscani Tumori, Florence, Italy.
The study found that clinical assays for hormone receptor (HR) and HER2 expression in breast cancer do not perfectly align with intrinsic subtypes. Identifying basal-like breast cancer requires a low HR expression threshold (<1%) for accuracy.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Accurate breast cancer subtyping is crucial for treatment selection.
- Quantitative assessment of hormone receptor (HR) and HER2 expression is key.
- Intrinsic subtypes offer a more precise classification than traditional methods.
Purpose of the Study:
- To correlate intrinsic breast cancer subtypes with categories defined by quantitative hormone receptor (HR) and HER2 expression.
- To evaluate the effectiveness of current clinical assay cutoffs for identifying specific intrinsic subtypes.
Main Methods:
- A pooled analysis of 1,557 patients from three phase III clinical trials.
- Centralized review of tumor samples for quantitative ER, PR, and HER2 expression using immunohistochemistry (IHC) and RT-qPCR.
- Intrinsic subtyping performed using research-based PAM50 RT-qPCR assay.
Main Results:
- Among HER2-negative tumors with <1% HR expression by IHC, 73% were basal-like, but other subtypes were also present.
- Tumors with borderline HR expression (1%-9%) were molecularly diverse, with a mix of luminal, HER2-enriched, and basal-like subtypes.
- Basal-like tumors rarely expressed ER/ESR1 or PR/PGR and showed the lowest HER2/ERBB2 expression levels, irrespective of the quantification method.
Conclusions:
- Significant discordance exists between clinical assay-defined breast cancer subsets and intrinsic subtypes.
- An HR IHC cutoff of <1% is optimal for identifying basal-like breast cancer, aligning with current guidelines.
- Tumors with borderline HR expression require further molecular assays for accurate biological classification.
