Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy

Abstract

The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB) samples using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

Figure 1. OPLS-DA score and loadinig S-plots of the HR-MAS MR spectra for predicting pathologic response to NAC.

(A) pCR vs. PR (B) pCR vs. SD (C) PR vs. SD. pCR: pathologic complete response; PR: partial response; SD: stable disease.

Figure 2. OPLS-DA score and loading S-plot of the HR-MAS MR spectra for differentiating pCR from non-pCR.

(A) OPLS-DA score and loading S-plot of the HR-MAS MR spectra from pCR and non-pCR (PR and SD) groups. Representative spectra of the tumors showing pCR (B) and non-pCR (C) to NAC. pCR: pathologic complete response; PR: partial response; SD: stable disease. Cho: choline; PC: phosphocholine; GPC: glycerophosphocholine; tCho: total choline (the sum of Cho, PC, and GPC); Cr: creatine; Tau: taurine; Gly: glycine; m-Ins: myo-inositol; Ala: alanine; Suc: succinate; Lys: lysine; Ace: acetate; Val: valine; Iso: isoleucine.