Molecular profiling of triple negative breast cancer

2011 ◽  
Vol 32 (1-2) ◽  
pp. 73-84 ◽  
Author(s):  
Cynthia X. Ma ◽  
Jingqin Luo ◽  
Matthew J. Ellis
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Profiling

Evaluation of predictive biomarkers for AR therapy and to identify the LAR subtype of TNBC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 595-595
Author(s):  
Sahil Seth ◽  
James Crespo ◽  
Lei Huo ◽  
Alastair Mark Thompson ◽  
Elizabeth A. Mittendorf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Biomarkers ◽  
Immunohistochemical Analysis ◽  
Predictive Biomarker ◽  
Molecular Profiling ◽  
Molecular Signature

595 Background: Androgen-receptor-like (LAR) triple-negative breast cancer (TNBC) is a subtype identified using Vanderbilt’s molecular signature. LAR subtype has the lowest pCR rate for NACT among all TNBC subtypes (10% vs. 28% for TNBC in general). We launched a clinical trial to determine the effectiveness of enzalutamide and paclitaxel (ZT) in improving this poor chemo. response in the neoadjuvant setting for pts with anthracycline-refractory, androgen receptor (AR)+ TNBC (NCT02689427). However, we do not yet have a robust predictive biomarker to detect an activated AR pathway and have not seen a robust correlation between molecular LAR subtype and AR IHC staining intensity. Methods: Molecular profiling and immunohistochemical analysis of key biomarkers (LAR, Ki67, and vimentin) was performed for all pts enrolled in A Randomized triple negative breast cancer enrolling Trial to Confirm Molecular Profiling Improves Survival (ARTEMIS; NCT02276443). Patients receive 4 cycles of AC, followed by an experimental arm or standard taxane, tailored using nuclear IHC staining. IHC staining of ≥30% AR+ was used as a threshold for selection for enzalutamide combination arm. We evaluated the concordance between LAR-subtype using molecular profiling vs % AR+ cells via IHC. Results: As part of the clinical trial, tumors with ≥30% AR+ cells were classified as LAR. In addition, we used RNA profiling to assign Vanderbilt subtype scores, resulting in classification of 15 tumors as LAR+. We observed a significant correlation (r=0.75) between LAR score and %AR+ cells, with 13 of 15 LAR tumors having ≥30% AR+ cells. Among patients with high % of AR+ tumor cells, 11 received enzalutamide, with 43% (3/7) having responses (pCR or RCB-I). Conclusions: Comparison on numerical scores for Vanderbilt subtype and IHC scores suggests ≥30% AR+ IHC staining as the threshold (ppv=0.65, npv=0.98, Table) to identify the molecular LAR subtype. We observed a trend where response rate was higher in patients with ≥ AR+ IHC scores treated with enzalutamide; however, these results need confirmation in a larger cohort of patients. Clinical trial information: NCT02689427, NCT02276443. [Table: see text]

Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients

2007 ◽  
Vol 111 (1) ◽  
pp. 27-44 ◽  
Author(s):  
David S. P. Tan ◽  
Caterina Marchió ◽  
Robin L. Jones ◽  
Kay Savage ◽  
Ian E. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Profiling ◽  
Prognostic Impact
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