Metastatic HR+ Breast Cancer Research Protocol

Patients with metastatic HR+ breast cancer were offered participation in a prospective research protocol to obtain a research sample at the time of their clinical biopsy of metastasis at MD Anderson (protocol LAB04-0093) between 2004 and 2013, obtained as fine-needle aspiration (FNA) or core biopsy (CBX). Their next treatment was recorded and was at the discretion of their oncologist. A total of 234 samples were profiled using Affymetrix U133A gene expression microarrays, 212 microarrays passed our quality control analysis. We excluded 32 HER2-positive and 26 hormone receptor-negative cases based on immunohistochemistry and (where appropriate) HER2 in situ hybridization testing of the metastatic samples. Fourteen additional cases were excluded for other reasons (no follow-up data after biopsy, diagnosis other than breast cancer), resulting in 140 eligible cases with quality microarray data in this study (GSE124647). Median PFS and OS were 5.5 and 24.0 months, respectively (Table 1). PR positivity was defined as ≥10% nuclear immunostaining. Proliferation (Ki-67 immunohistochemistry) is not usually assessed in metastatic samples, so we evaluated Aurora kinase-A (AURKA; probe set 208079_s_at) as a reliable genomic marker for proliferation in multivariate survival analyses.^{33 (link)} The clinical variable of prior endocrine sensitivity was defined as a history of at least 6 months of freedom from progression while on endocrine therapy for metastatic disease or 5 years adjuvant endocrine therapy for primary breast cancer without recurrence. A subset of 53 cases was available for analysis of ESR1 gene mutations by RNAseq.