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][2][3][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 (SUV max ), during 18 F-FDG PET/CT. High SUV max 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][8][9][10][11][12].In the present issue of the European Journal of Nuclear Medicine and Molecular Imaging, García 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 de...

Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives

“…Therefore, the evaluation of the specific disease process using the multi-tracer approach may be of more value than imaging with a non-specific tracer like [ 18 F]FDG. More useful information may be obtained from the imaging of both ER-positivity and tumor glucose metabolism than the imaging of either process without the other [83][84][85].…”

Combined 18F-FDG and 18F-Alfatide II PET May Predict Luminal B (HER2 Negative) Subtype and Nonluminal Subtype of Invasive Breast Cancer

“…The invasiveness makes it hard to be repeatable and difficult to evaluate the dynamic changes of breast cancer regarding these molecular markers during treatment. Moreover, a histological sample only reflects a small part of breast cancer and is insufficient to present the markers’ status over the whole tumor. , Additionally, there exists a discrepancy between the primary lesion and the metastatic lesion with regard to the expression levels of the markers . Thus, even if a molecular marker is positive in the primary lesion, it can be negative in the metastatic lesion.…”

“…6,7 Additionally, there exists a discrepancy between the primary lesion and the metastatic lesion with regard to the expression levels of the markers. 8 Thus, even if a molecular marker is positive in the primary lesion, it can be negative in the metastatic lesion. Therefore, a safe, noninvasive, and highly repeatable method that can dynamically and comprehensively assess the molecular markers for the primary lesion of breast cancer, as well as the metastases, is essential.…”