Literature DB >> 25908555

Defining breast cancer intrinsic subtypes by quantitative receptor expression.

Maggie C U Cheang1, Miguel Martin1, Torsten O Nielsen1, Aleix Prat1, David Voduc1, Alvaro Rodriguez-Lescure1, Amparo Ruiz1, Stephen Chia1, Lois Shepherd1, Manuel Ruiz-Borrego1, Lourdes Calvo1, Emilio Alba1, Eva Carrasco1, Rosalia Caballero1, Dongsheng Tu1, Kathleen I Pritchard1, Mark N Levine1, Vivien H Bramwell1, Joel Parker1, Philip S Bernard1, Matthew J Ellis1, Charles M Perou1, Angelo Di Leo1, Lisa A Carey2.   

Abstract

PURPOSE: To determine intrinsic breast cancer subtypes represented within categories defined by quantitative hormone receptor (HR) and HER2 expression.
METHODS: We merged 1,557 cases from three randomized phase III trials into a single data set. These breast tumors were centrally reviewed in each trial for quantitative ER, PR, and HER2 expression by immunohistochemistry (IHC) stain and by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with intrinsic subtyping by research-based PAM50 RT-qPCR assay.
RESULTS: Among 283 HER2-negative tumors with <1% HR expression by IHC, 207 (73%) were basal-like; other subtypes, particularly HER2-enriched (48, 17%), were present. Among the 1,298 HER2-negative tumors, borderline HR (1%-9% staining) was uncommon (n = 39), and these tumors were heterogeneous: 17 (44%) luminal A/B, 12 (31%) HER2-enriched, and only 7 (18%) basal-like. Including them in the definition of triple-negative breast cancer significantly diminished enrichment for basal-like cancer (p < .05). Among 106 HER2-positive tumors with <1% HR expression by IHC, the HER2-enriched subtype was the most frequent (87, 82%), whereas among 127 HER2-positive tumors with strong HR (>10%) expression, only 69 (54%) were HER2-enriched and 55 (43%) were luminal (39 luminal B, 16 luminal A). Quantitative HR expression by RT-qPCR gave similar results. Regardless of methodology, basal-like cases seldom expressed ER/ESR1 or PR/PGR and were associated with the lowest expression level of HER2/ERBB2 relative to other subtypes.
CONCLUSION: Significant discordance remains between clinical assay-defined subsets and intrinsic subtype. For identifying basal-like breast cancer, the optimal HR IHC cut point was <1%, matching the American Society of Clinical Oncology and College of American Pathologists guidelines. Tumors with borderline HR staining are molecularly diverse and may require additional assays to clarify underlying biology. ©AlphaMed Press.

Entities:  

Keywords:  Breast cancer; Intrinsic subtypes; Receptor expression

Mesh：

Substances：

Year:  2015        PMID： 25908555      PMCID： PMC4425383          DOI： 10.1634/theoncologist.2014-0372

Source DB:  PubMed          Journal:  Oncologist        ISSN： 1083-7159


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