Early detection of changes in phospholipid metabolism during neoadjuvant chemotherapy in breast cancer patients using phosphorus magnetic resonance spectroscopy at 7T.

Paul J. Diest,Wybe J.M. Kemp,Dennis W.J. Klomp,Jannie P. Wijnen,Peter R. Luijten,Hanneke W.M. Laarhoven,Erwin Krikken,Thijs Dalen

doi:10.1002/nbm.4086

Abstract

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31P‐MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31P‐MRSI was performed in 12 breast cancer patients treated with NAC. 31P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in‐organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki‐67 levels was determined using linear regression.Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki‐67 index was found (P = 0.03).We demonstrated that it is possible to detect subtle changes in 31P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.

Highlights

Breast cancer is the most common cancer in women worldwide.[1]
In previous work examining the feasibility of measuring in vivo changes in phospholipid metabolites during Neoadjuvant chemotherapy (NAC) using 31P‐MRSI,[24] we reported decreased PME/PDE and PME/in‐organic phosphate (Pi) halfway through and after the end of NAC
All three human epidermal growth factor receptor 2 (HER2)+ subtypes had a complete response to NAC treatment

Summary

Introduction

Breast cancer is the most common cancer in women worldwide.[1]. Neoadjuvant chemotherapy (NAC) is increasingly used for presurgical treatment with the main purpose of downsizing locally advanced tumors to make them better candidates for resection.[2]. It has been shown that the desired tumor size reduction is not accomplished with NAC in up to 31% of patients who will have stable or even progressive disease.[4] In order to identify patients who will have stable or progressive disease, it is important to identify biomarkers that can assess the response to NAC at an early stage in the individual patient. This could enable the adjustment of systemic therapy and avoid toxicity and the related costs of ineffective treatment

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Conclusion