Abstract
Here we investigate the feasibility of tumor metabolism monitoring in T1c to T3 breast cancer during neoadjuvant chemotherapy by means of phosphorus (31P) magnetic resonance spectroscopy at 7 tesla (T). Five breast cancer patients were examined using a 31P MRSI sequence, prior to-, halfway-, and after neoadjuvant chemotherapy. The 31P MRSI data were analyzed on group and individual level and compared to a spectrum of a group of healthy volunteers. Ratios of phosphomonoesters (PME) to phosphodiesters (PDE) and phosphomonoesters to inorganic phosphate (Pi) were determined. Histopathologic assessment showed four partial responders and one complete responder to chemotherapy. The 31P spectrum of the patient group was distinctly different from the 31P spectrum of healthy volunteers and transformed its shape during the course of chemotherapy towards the shape of the spectrum of the healthy volunteers. Prior to chemotherapy the PME to PDE signal ratio and the PME to Pi signal ratio were high, and during the course of the chemotherapy these ratios normalized to the value of the healthy volunteers. Metabolite T2 values in tumor tissue tended to be lower than those for healthy glandular tissue. Assessment of individual patients showed that four out of five had a significant drop of the PME to Pi ratio by a factor of 2 or more. On average, the pH of the tumor, calculated from chemical shift variation of Pi, was 0.19 units lower before chemotherapy. We have demonstrated that the sensitivity of 31P MRSI in breast cancer at 7 T is sufficient to detect alterations in membrane metabolism during neoadjuvant chemotherapy, which may be used for early assessment of treatment efficacy.
Highlights
Breast cancer is by far the most prevalent type of cancer in women worldwide (Jemal et al 2011)
Reduction of the tumor volume is achieved in the majority of patients, a pathologic complete response is only seen in less than 20% of patients according to a recent meta-analyses which included almost
3800 breast cancer patients receiving neoadjuvant therapy (Kong et al 2011). Because of this low pathologic complete response that is often used to predict survival rate, there is a need for early assessment of neoadjuvant chemotherapy efficacy, which would enable switching to a possibly more successful agent early in therapy
Summary
Breast cancer is by far the most prevalent type of cancer in women worldwide (Jemal et al 2011). In this work we investigate whether state of the art 31P MRSI is sufficiently sensitive to pick up PME alterations in the primary tumor in patients with breast cancer during the course of neoadjuvant chemotherapy.
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