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Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies.
- Source :
-
Cancer Cell . Jun2022, Vol. 40 Issue 6, p609-609. 1p. - Publication Year :
- 2022
-
Abstract
- Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from ∼990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization. [Display omitted] • The I-SPY2-990 Data Resource contains mRNA, protein, and response data over 10 drugs • Biomarkers are combined to create breast cancer subtypes to match modern treatments • Best subtyping schemas incorporate Immune, DNA repair, Luminal, and HER2 phenotypes • Treatment assignment using these response predictive subtypes may improve outcomes Wolf et al. use gene expression, protein levels, and response data from 10 drug arms of the I-SPY2 neoadjuvant trial to create new breast cancer subtypes that incorporate tumor biology beyond clinical hormone receptor (HR) and HER2 status. Use of these response-predictive subtypes to guide treatment prioritization may improve patient outcomes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 40
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 157329864
- Full Text :
- https://doi.org/10.1016/j.ccell.2022.05.005