Vol 106: Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer.Report as inadecuate



 Vol 106: Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer.


Vol 106: Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 106: Molecular Features and Survival Outcomes of the Intrinsic Subtypes Within HER2-Positive Breast Cancer.
This article is from JNCI Journal of the National Cancer Institute, volume 106.AbstractBackground: The clinical impact of the biological heterogeneity within HER2-positive HER2+ breast cancer is not fully understood. Here, we evaluated the molecular features and survival outcomes of the intrinsic subtypes within HER2+ breast cancer. Methods: We interrogated The Cancer Genome Atlas n = 495 and Molecular Taxonomy of Breast Cancer International Consortium METABRIC datasets n = 1730 of primary breast cancers for molecular data derived from DNA, RNA and protein, and determined intrinsic subtype. Clinical HER2 status was defined according to American Society of Clinical Oncology ASCO-College of American Pathologists CAP guidelines or DNA copy-number aberration by single nucleotide polymorphism arrays. Cox models tested the prognostic significance of each variable in patients not treated with trastuzumab n = 1711. Results: Compared with clinically HER2 cHER2-negative breast cancer, cHER2+ breast cancer had a higher frequency of the HER2-enriched HER2E subtype 47.0% vs 7.1% and a lower frequency of Luminal A 10.7% vs 39.0% and Basal-like 14.1% vs 23.4% subtypes. The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype, only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was statistically significantly higher in the HER2E and Basal-like subtypes than either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number-based classification system IntClust added independent prognostic value to intrinsic subtype. Conclusions: When the intrinsic subtypes are taken into account, cHER2-positivity does not translate into large changes in the expression of downstream signaling pathways, nor does it affect patient survival in the absence of HER2 targeting.



Author: Prat, Aleix; Carey, Lisa A.; Adamo, Barbara; Vidal, Maria; Tabernero, Josep; Cortes, Javier; Parker, Joel S.; Perou, Charles M.; Baselga, Jose

Source: https://archive.org/







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