Gene expression analysis to detect disseminated tumor cells in the bone marrow of triple-negative breast cancer patients predicts metastatic relapse

Chidananda M. Siddappa, Sreeraj G. Pillai, Jackie Snider, Patsy Alldredge, Kathyrn Trinkaus, Mark A. Watson, Rebecca Aft

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse. Methods: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed. Results: Expression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0–84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%. Conclusions: We identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC.

Original languageEnglish
Pages (from-to)317-325
Number of pages9
JournalBreast Cancer Research and Treatment
Volume178
Issue number2
DOIs
StatePublished - Nov 1 2019

Keywords

  • Disseminated tumor cells
  • Gene expression
  • Metastasis
  • Targeted therapy
  • Triple-negative breast cancer

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