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Relationship between functional imaging and immunohistochemical markers and prediction of breast cancer subtype: a PET/MRI study

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Abstract

Purpose

The aim of this study was to determine if functional parameters extracted from the hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) correlate with the immunohistochemical markers of breast cancer (BC) lesions, to assess their ability to predict BC subtype.

Methods

This prospective study was approved by the institution’s Ethics Committee, and all patients provided written informed consent. A total of 50 BC patients at diagnosis underwent PET/MRI before pharmacological and surgical treatment. For each primary lesion, the following data were extracted: morphological data including tumour-node-metastasis stage and lesion size; apparent diffusion coefficient (ADC); perfusion data including forward volume transfer constant (Ktrans), reverse efflux volume transfer constant (Kep) and extravascular extracellular space volume (Ve); and metabolic data including standardized uptake value (SUV), lean body mass (SUL), metabolic tumour volume and total lesion glycolysis. Immunohistochemical reports were used to determine receptor status (oestrogen, progesterone, and human epidermal growth factor receptor 2), cellular differentiation status (grade), and proliferation index (Ki67) of the tumour lesions. Correlation studies (Mann–Whitney U test and Spearman’s test), receiver operating characteristic (ROC) curve analysis, and multivariate analysis were performed.

Results

Association studies were performed to assess the correlations between imaging and histological prognostic markers of BC. Imaging biomarkers, which significantly correlated with biological markers, were selected to perform ROC curve analysis to determine their ability to discriminate among BC subtypes. SUVmax, SUVmean and SUL were able to discriminate between luminal A and luminal B subtypes (AUCSUVmean = 0.799; AUCSUVmax = 0.833; AUCSUL = 0.813) and between luminal A and nonluminal subtypes (AUCSUVmean = 0.926; AUCSUVmax = 0.917; AUCSUL = 0.945), and the lowest SUV and SUL values were associated with the luminal A subtype. Kepmax was able to discriminate between luminal A and luminal B subtypes (AUC = 0.779), and its highest values were associated with the luminal B subtype. Ktransmax (AUC = 0.881) was able to discriminate between luminal A and nonluminal subtypes, and the highest perfusion values were associated with the nonluminal subtype. In addition, ADC (AUC = 0.877) was able to discriminate between luminal B and nonluminal subtypes, and the lowest ADCmean values were associated with the luminal B subtype. Multivariate analysis was performed to develop a prognostic model, and the best predictive model included Ktransmax and SUVmax parameters.

Conclusion

Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktransmax and SUVmax was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%).

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Funding

This study was supported by “Ricerca Corrente” funding from the Italian Ministry of Health and partially by “5 per mille” IRCCS SDN grant.

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Author notes

  1. Mariarosaria Incoronato and Anna Maria Grimaldi contributed equally to this work.

Authors and Affiliations

  1. IRCCS SDN, Via Gianturco n 113, Naples, Italy

    Mariarosaria Incoronato, Anna Maria Grimaldi, Carlo Cavaliere, Marianna Inglese, Peppino Mirabelli, Serena Monti, Emanuele Nicolai, Andrea Soricelli, Marco Aiello & Marco Salvatore

  2. Department of Pathology, Ospedale Moscati, Avellino, Italy

    Umberto Ferbo

  3. Department of Motor Sciences & Healthiness, University of Naples Parthenope, Naples, Italy

    Andrea Soricelli

  4. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Onofrio Antonio Catalano

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  1. Mariarosaria Incoronato
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Correspondence to Mariarosaria Incoronato.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the institutional Ethics Committee (Prot2-11, IRCCS Fondazione SDN). This article does not describe any studies with animals performed by any of the authors.

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Incoronato, M., Grimaldi, A.M., Cavaliere, C. et al. Relationship between functional imaging and immunohistochemical markers and prediction of breast cancer subtype: a PET/MRI study. Eur J Nucl Med Mol Imaging 45, 1680–1693 (2018). https://doi.org/10.1007/s00259-018-4010-7

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