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.

Keywords: 18F-Fluorodeoxyglucose; Breast; Cancer; Monitoring; Positron emission tomography; Response.

Figure 1.

Example of fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) exam before (left) and after (right) 3 months of eribulin and trastuzumab therapy in a woman with an osteolytic metastases of breast cancer, located on TH12 . After treatment, CT showed an important sclerotic reaction of the bone lesion, whereas PET showed no more metabolic activity. Both the anatomic and molecular imaging are in favor of a good response to systemic treatment.

Figure 2.

Discordant response between bone and visceral metastases on fluorodeoxyglucose (FDG)-positron emission tomography (PET) exams performed before (left) and after (right) 3 months of treatment with gemcitabine-trastuzumab. Baseline FDG-PET shows hypermetabolic activity in bilateral and multifocal breast tumors, lymph node involvement of right axilla, and bone metastases. After treatment, PET demonstrated an heterogeneous metabolic response with coexistence of responding (left breast, axillary nodes) and nonresponding metastatic bone lesions (red arrows, moderate increased in focal uptake of the two bone lesions).

Figure 3.

FDG-PET exam (left) and FES-PET exam (right) of a woman with metastatic breast cancer. The tumor lesions, assessed with FDG-PET, showed heterogeneous expression of estrogen receptors: primary breast tumor had a high but heterogeneous uptake pattern of FES, mediastinal nodes showed no significant FES uptake, and the bone metastasis on the left ischiopubic branch showed weak FES uptake. The liver metastasis was not evaluable with FES-PET because of the high physiological uptake of the liver (images are obtained from Estrotepredic Programme Hospitalier de Recherche Clinique, coordinator: Dr. K. Kerrou, Hôpital Tenon, Assistance-Publique–Hôpitaux de Paris, Paris; Eudract: 2011-005043-27). Abbreviations: FDG, fluorodeoxyglucose; FES, 16α-¹⁸F-fluoro-17β-estradiol; PET, positron emission tomography.