Role of Positron Emission Tomography for the Monitoring of Response to Therapy in Breast Cancer

Abstract

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with 18 F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype.The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor. The Oncologist 2015;20:94-104 Implications for Practice:18 F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a molecular imaging exam. It can monitor breast cancer response to therapy earlier than the tumor shrinking observed with conventional imaging. This review focuses on the advantages and limits of FDG-PET for early determination of response, both in the neoadjuvant and metastatic settings. It discusses the different PET timing and metabolic criteria to define response that have been evaluated in previous studies. The development of new radiotracers of specific molecular pathways of breast cancer cells is also a challenging and promising research area to monitor the effectiveness of the new target treatments emerging in breast cancer.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

“…The first necessity is developing a more rational approach to clinical trial design. For example, Humber et al 26 appealed for more randomized trials to demonstrate a clinical benefit of an early tailoring of the induction treatment in breast cancer by PET imaging; Jauw et al 27 also proposed several approaches to evaluating the clinical application of PET imaging to guide individualized treatment. During the design of a trial, clinicians and other relevant parties (e.g., academic institutions, regulators, clinical research organizations) should make concerted efforts to ensure that the trial design reflects the characteristics of a specific condition as well as pertinent clinical questions.…”

Molecular Imaging of Biomarkers in Breast Cancer

“…This lack of uniformity makes comparison of studies more difficult. In addition, rates of pCR and implications of pCR depend on the receptor status of the primary tumor (48,49). And despite some support for using pCR to predict improved outcomes, a large metaanalysis evaluating pCR, comprising nearly 12,000 patients, did not find pCR to be a surrogate endpoint for improvement of overall survival by neoadjuvant chemotherapy (50).…”

“…An in-depth analysis of 18 F-FDG PET/CT for the prediction of neoadjuvant response evaluation in patients with breast cancer is detailed in a separate article (51) in this issue; however, a few concepts are worth emphasizing here. First, the ability of 18 F-FDG PET/CT to predict pCR may depend on the ER and HER2 receptor status of the primary breast malignancy (49). Second, the metric for quantifying 18 F-FDG uptake, such as SUV max or metabolic tumor volume, that optimally determines neoadjuvant response may differ for tumors of different receptor status (50).…”

“…The ER and HER2 receptor status of breast malignancies influences changes in the 18 F-FDG avidity of these cancers after treatment (49,52) and should therefore be considered when evaluating treatment response with 18 F-FDG PET/CT.…”

Development of Companion Diagnostics

“…69 Further prospective studies are needed to validate these early findings. 70 Although the absence of FES uptake indicates a low likelihood of response, the presence of FES uptake does not guarantee endocrine responsiveness. This is analogous to tissue assay for ER where absent ER reliably predicts a lack of endocrine responsiveness, but a positive assay predicts response less reliably.…”