Imaging Correlates between Headache and Breast Cancer: An [(18)F]FDG PET Study

SIMPLE SUMMARY: [(18)F]Fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) provides information about metabolic patterns of different diseases and conditions. This study aimed to prospectively evaluate patients with breast cancer in order to describe specific brain metabolic patterns related to the presence or absence of primary forms of headache, namely tension-type headache (TTH) and migraine (MiG). Moreover, we explored the association between primary headache forms and BC response to neoadjuvant chemotherapy (NAC). We observed a high rate of headache in the 46 BC analyzed patients. TTH patients exhibited areas of hypometabolism in specific brain regions before NAC. Moreover, our results suggest an association between primary headache, especially MiG, and treatment response to NAC. Collectively, our results support the hypothesis of a complex and dynamic interplay among BC, headache, and hormonal status. ABSTRACT: This study aimed to examine brain metabolic patterns on [(18)F]Fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) in breast cancer (BC), comparing patients with tension-type headache (TTH), migraine (MiG), and those without headache. Further association with BC response to neoadjuvant chemotherapy (NAC) was explored. In this prospective study, BC patients eligible for NAC performed total-body [(18)F]FDG PET/CT with a dedicated brain scan. A voxel-wise analysis (two-sample t-test) and a multiple regression model were used to compare brain metabolic patterns among TTH, MiG, and no-headache patients and to correlate them with clinical covariates. A single-subject analysis compared each patient’s brain uptake before and after NAC with a healthy control group. Primary headache was diagnosed in 39/46 of BC patients (39% TTH and 46% MiG). TTH patients exhibited hypometabolism in specific brain regions before NAC. TTH patients with a pathological complete response (pCR) to NAC showed hypermetabolic brain regions in the anterior medial frontal cortex. The correlation between tumor uptake and brain metabolism varied before and after NAC, suggesting an inverse relationship. Additionally, the single-subject analysis revealed that hypometabolic brain regions were not present after NAC. Primary headache, especially MiG, was associated with a better response to NAC. These findings suggest complex interactions between BC, headache, and hormonal status, warranting further investigation in larger prospective cohorts.