PET/CT and breast cancer subtypes

Abstract

Breast cancer is a profoundly heterogeneous disease that includes a number of distinct entities with specific pathological features, biological behaviours and different sensitivities to systemic and targeted therapies [1–4]. The recent development of high-throughput molecular methods offers new opportunities to capture the wide range of this variability. Indeed, the novel molecular techniques of gene expression profiling permit evaluation of the expression of thousands of genes in a large number of tumours, so that a fully comprehensive portrait or profile of the different molecular pathways can be obtained. The reproducibility and the clinical usefulness of assays based on gene expression have been demonstrated with increasing confidence over the past decade, but cost considerations limit the wide availability of these techniques [5]. Immunohistochemical (IHC) determination of oestrogen and progesterone receptors (ER and PgR), the detection of overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) and the Ki67 labelling index have been defined as a convenient alternative to molecular subtyping and are considered a sufficient to guide therapeutic choices [6]. Several studies have investigated the correlation between these clinical/pathological prognostic and predictive markers and the levels of radiotracer uptake by primary breast tumours, measured as maximum standardized uptake value (SUVmax), during F-FDG PET/CT. High SUVmax was found to be significantly correlated with ER negativity, PgR negativity, triple negativity and Ki67 values, while conflicting results were found for the relationship with HER2 status [7–12]. In the present issue of the European Journal of Nuclear Medicine and Molecular Imaging, Garcia Vicente et al. take a step forward in this approach to evaluation. They analysed the correlation between the glycolytic characteristics of primary breast tumours and their molecular subtypes. The authors prospectively evaluated 168 patients who were submitted to FDG PET/CT before neoadjuvant therapy for locally advanced breast cancer. Tumour subtypes were classified by IHC surrogates as luminal A, luminal B-HER2(−), luminal B-HER2(+), HER2(+) or basal (triple negative), following the recommendations of the 12th St Gallen International Breast Cancer Conference. Statistically significant differences were found in semiquantitative metabolic parameters among the different subtypes, with greater values in HER2(+) and basal tumours [13]. These results are not unexpected, as the relationship between increased glucose metabolism and tumour aggressiveness is well known. This is one of the first studies demonstrating a correlation between molecular and glycolytic phenotypes of breast cancer. Humbert et al. found that baseline FDG uptake of primary tumours and its early response to neoadjuvant chemotherapy may vary according to the IHC subtype of the breast cancer. Triple-negative tumours showed the highest baseline SUV. After the first course of therapy the decrease in SUV was significantly higher in triple-negative and HER2-positive subtypes. Pathological complete response (pCR) occurred more often in these two subtypes, rather than in luminal tumours, and the relative change in SUV was predictive of pCR only in HER2-positive tumours with an accuracy of 76 % [14]. Zhang et al. evaluated 244 patients with metastatic breast cancer. They found that molecular subtype, visceral metastases and number of organs bearing metastases could be used to predict logarithmic values of SUVmax only in previously untreated metastatic breast cancer [15]. L. Gilardi :G. Paganelli (*) Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy e-mail: divisione.medicinanucleare@ieo.it