Dallas Surgical Group, Dallas, TX
Peter D. Beitsch , Lisette Stork , Femke De Snoo , Justine Peeters , Pat W. Whitworth
Background: TheraPrint for breast cancer patients is a novel genomic assay that provides information on clinically relevant markers for likely sensitivity and resistance to therapies. The aim of the current study was to correlate chemosensitivity in a neo-adjuvant trial to TheraPrint results. Methods: The mRNA level of 55 genes was measured in formalin fixed paraffin embedded (FFPE) tumor samples submitted from 42 institutes in the US as part of the NBRST trial and compared to a large reference population (TheraPrint). The prospective Neo-adjuvant Breast Registry Symphony Trial (NBRST) study includes informed consenting women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemo- or endocrine therapy. The correlation of chemosensitivity to TheraPrint results is measured by pathologic Complete Response (pCR) defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resected specimen, regardless of the presence of carcinoma in-situ. Differentially expressed genes were identified by Analysis of Variance (ANOVA) with corrected p-value (FDR) <0.05. Results: 204 Patients (T1-4 N0-3) received neo-adjuvant chemotherapy and had definitive surgery. The overall pCR rate was 24%. Listed in the table are those genes that were significantly differentially expressed between patients with a pCR versus those with residual disease (p>0.05, Fold change >1.5). Conclusions: This study has identified 13 genes with statistically significant correlation between expression and response to neo-adjuvant chemotherapy indicating that TheraPrint can give indication for response prediction to chemotherapy. Clinical trial information: NCT014799101.
TheraPrint gene |
Corrected p-value |
Fold change |
Up or downregulated in patients with pCR |
---|---|---|---|
Ki67 | 0.01473 | 1.2 | ↑ |
LYN | 0.01803 | 1.2 | ↑ |
EPHA2 | 0.05190 | 1.3 | ↑ |
MET | 0.05190 | 1.3 | ↑ |
ESR1 | <0.00000 | -3.3 | ↓ |
ESR2 | 0.00077 | -1.6 | ↓ |
PgR | 0.00002 | -2.4 | ↓ |
CCND1 | 0.00077 | -1.6 | ↓ |
IGF1R | 0.00387 | -1.7 | ↓ |
HER3 | 0.01473 | -1.6 | ↓ |
HER4 | 0.00412 | -1.7 | ↓ |
BCL2 | 0.01797 | -1.6 | ↓ |
AR | 0.01803 | -1.5 | ↓ |
This list of genes is significantly associated with PTEN activation, ER inhibition and estrogen-related signaling pathways (Ingenuity Pathway Analysis).
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