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ColXα1 and Tumor Infiltrating Lymphocytes: a Marker of Response to Neoadjuvant Therapy in Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

ABSTRACT: This study focused on patients with estrogen receptor positive/human epidermal growth factor receptor 2 positive (ER+/HER2+) breast cancer treated with neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel biomarkers by correlating gene expression, histology and immunohistochemistry with pathologic response. We performed gene expression profiling on 11 pre-treatment tumors samples: 5 who had no or minimal residual disease residual cancer burden (RCB) score of 0 or 1 and 6 who had significant residual disease (RCB score of 2 or 3).

ORGANISM(S): Homo sapiens

PROVIDER: GSE67982 | GEO | 2015/09/08

SECONDARY ACCESSION(S): PRJNA281505

REPOSITORIES: GEO

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Project description:Introduction: The I-SPY 1 TRIAL was designed to evaluate complete pathologic response and tumor volume change, measured by magnetic resonance imaging (MRI), stratified by molecular subtypes and link response to 3-year recurrence free survival (RFS).Methods: Eligible patients had T =3 cm and received neoadjuvant chemotherapy with AC plus optional taxane. Serial MRI, biopsy, and blood draws were conducted over the course of treatment, and a database of multiple molecular profiles was assembled.Results: A total of 221 patients were eligible for analysis: median tumor size was 6.0 cm and median age was 49 years. The I-SPY 1 TRIAL patients had tumors with aggressive biology: 45% were estrogen receptor (ER) negative, 31% Her2+; and 91% high risk by the Netherlands Cancer Institute (NKI) 70-gene profile. After a median of 3.9 years, RFS was 77%. HR/HER2 status improved predictability of RFS with the greatest difference between HR+/HER2- and triple-negative disease (hazard ratio 0.39). Wound healing signature activation, p53 mutation, and Risk of Relapse (ROR) score were highly correlated and also significantly improved the accuracy of RFS predictions when added to stage. The rate of pathologic complete response (pCR) varied considerably from a low of 0-2% (NKI low risk, luminal A) to a high of 43-61% (17q Amplified, HER2 enriched, HR-/HER2+). Both pCR and the more refined residual cancer burden (RCB) were significant predictors of RFS for all patients and even more predictive when analyzed within biomarker subsets. Good risk (NKI low, ROR-S low risk, Wound Healing quiescent, p53 wild type) signatures were associated with significantly higher 3-year RFS than poor risk expression signatures (ROR-S high risk, Wound Healing Activated, p53 mutation, NKI high risk).Conclusion: Importantly, in this set of biologically poor prognosis tumors, pCR predicts for better outcome, especially when analyzed within breast cancer subsets. Keywords: reference x sample reference x sample

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ColXα1 and Tumor Infiltrating Lymphocytes: a Marker of Response to Neoadjuvant Therapy in Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

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