Data from High <i>XIST</i> and Low 53BP1 Expression Predict Poor Outcome after High-Dose Alkylating Chemotherapy in Patients with a <i>BRCA1</i>-like Breast Cancer

Abstract

<div>Abstract<p>In previous studies, high expression of <i>XIST</i> and low expression of <i>53BP1</i> were respectively associated with poor systemic therapy outcome in patients and therapy resistance in <i>BRCA1</i>-deficient mouse tumor models, but have not been evaluated in <i>BRCA1</i>-deficient patients. Previously, we demonstrated that classifying breast cancer copy number profiles as <i>BRCA1</i>-like or non–<i>BRCA1</i>-like identified patients enriched for defects in <i>BRCA1</i> that benefit from high-dose (HD) alkylating chemotherapy compared with a conventional standard regimen. We investigated whether <i>XIST</i> and 53BP1 expression predicted poor outcome of HD chemotherapy within 28 <i>BRCA1</i>-like patients from a trial randomizing between HD [4 cycles 5-fluorouracil, epirubicin, cyclophosphamide (FEC) followed by 1 cycle HD carboplatin, thiotepa, cyclophosphamide] or conventional chemotherapy (5 cycles FEC), for which both <i>XIST</i> and 53BP1 statuses were available. High RNA expression of <i>XIST</i> (<i>n</i> = 5) and low protein expression of 53BP1 (<i>n</i> = 3) expression did not coincide. Patients with either one had poor outcome after treatment with HD chemotherapy, whereas patients with low expression of <i>XIST</i> and high expression of 53BP1 derived substantial benefit of this regimen on recurrence-free survival, disease-free survival, and overall survival, corroborating preclinical findings. <i>XIST</i> and 53BP1 may be predictive biomarkers in BRCA1-like breast cancer. <i>Mol Cancer Ther; 15(1); 190–8. ©2015 AACR</i>.</p></div>