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

This study aimed to examine brain metabolic patterns on [18F]Fluorodeoxyglucose ([18F]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 [18F]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.

The Role of Female Reproductive Hormones in the Association between Migraine and Breast Cancer: An Unanswered Question.

Accumulating epidemiological studies have investigated a possible interconnection between migraine (Mi) and breast cancer (BC) because of the strong link between these diseases and female reproductive hormones. This review aims to consolidate findings from epidemiological studies and explore biologically plausible hypothetical mechanisms related to hormonal pathways. Current evidence suggests a protective role of Mi in BC development, particularly in case-control studies but not in cohort ones. The inconsistency among studies may be due to several reasons, including diagnostic criteria for Mi and the age gap between the development of these two diseases. Furthermore, recent research has challenged the concept of a net beneficial effect of Mi on BC, suggesting a more complex relationship between the two conditions. Many polymorphisms/mutations in hormone-related pathways are involved in at least one of the two conditions. The most promising evidence has emerged for a specific alteration in the estrogen receptor 1 gene (rs2228480). However, the possible specific mutation or polymorphism involved in this association has not yet been identified. Further studies with robust methodologies are needed to validate the protective role of Mi in BC and fully elucidate the precise nature of this causal relationship.

Profiling the Spectrum of Headache Disorders on 440 Breast Cancer Patients: Highlights on Clinical and Pathological Mechanisms.

Although widely studied, the association between migraines (M) and breast cancer (BC) risk remains evasive. In this prospective single-center study, 440 early or locally advanced BC patients were enrolled at IRCCS Humanitas Research Hospital. Clinical and demographical data were collected. Those who suffered from headaches were evaluated with the International Classification of Headache Disorders. M was found to be significantly more prevalent in BC patients: 56.1% versus an expected prevalence of 17% in the global population. M patients showed a higher risk of having stage II or III BC than stage I, which was more frequently found in the non-headache population. Interestingly, the frequency of headache attacks was positively correlated with estrogen (r = 0.11, p = 0.05) and progesterone (r = 0.15, p = 0.007) expression, especially in patients with migraine without aura. The higher the expression of hormone receptors in BC, the higher the headache frequency. Moreover, patients suffering from headaches showed an overall earlier onset of BC. Our findings challenge the idea of a net preventive role of M on BC, suggesting a rather complex interaction in which M mostly influences some BC subtypes and vice versa. Further multi-center studies with extended follow-up are needed.

The Relationship among Bowel [18]F-FDG PET Uptake, Pathological Complete Response, and Eating Habits in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

Recently, the impact of patients' eating habits on both breast cancer (BC) management and inflammation have been proven. Here, we investigated whether inflammatory habits could correlate with baseline bowel [18]F-fluorodeoxyglucose (FDG) uptake and the latter, in turn, with pathological Complete Response (pCR) to neoadjuvant chemotherapy (NAC). We included stage I−III BC undergoing standard NAC at IRCCS Humanitas Research Hospital, Italy. Patients fulfilled a survey concerning eating/lifestyle behaviors and performed a staging [18]F-FDG positrone emission tomography/computed tomography (PET/CT). In the absence of data on the effects of individual foods, we aggregated drink and food intake for their known inflammatory properties. Data were recorded for 82 women (median age, 48). We found positive correlations between colon mean standardized uptake value (SUVmean) and pro-inflammatory drinks (alcohol and spirits; r = +0.33, p < 0.01) and foods (red and cured meats; r = +0.25, p = 0.04), and a significant negative correlation between rectum SUVmean and anti-inflammatory foods (fruits and vegetables; r = −0.23, p = 0.04). Furthermore, colon SUVmean was significantly lower in patients with pCR compared to non pCR (p = 0.02). Our study showed, for the first time, that patients' eating habits affected bowel [18]F-FDG uptake and that colon SUVmean correlated with pCR, suggesting that PET scan could be an instrument for identifying patients presenting unhealthy behaviors.

A pilot analysis of headache disorders in breast cancer patients.

INTRODUCTION: The interaction between breast cancer and migraine is complex and not fully elucidated. Large epidemiological studies point towards a beneficial effect of migraines on breast cancer (BC). We aimed to investigate the BC-migraine relationship, with strict data checks and clinical evaluations of both BC and common headache forms. METHODS: Consecutive BC patients were evaluated with the International Classification of Headache Disorders. Clinical data on the BC subtypes and treatments were collected. Parametric and nonparametric statistics were used according to data distributions. RESULTS: Fifty patients were recruited. The mean age was 53.5 ± 12.5 years; 42% were postmenopausal, 52% were premenopausal, and 6% were peri-menopausal. Eleven patients were diagnosed as luminal A, nine as luminal B, 24 as HER2-positive (HER2 +), six as triple-negative BC. Thirty-eight (76%) patients had hormone receptor-positive disease. Ninety-two percent received chemotherapy, 66% received endocrine therapy, and 52% received radiotherapy. Nine out of 50 reported a worsening of headache after systemic treatment. Migraine was diagnosed in 29 patients (18 with menstrual migraine), tension-type headache (TTH) in nine, and no headache in 12. Patients with migraine were younger (48.4 ± 10.7 vs. 60.5 ± 12; p < 0.01). Patients with migraine and TTH had a higher chance of having a HER2 + BC (p < 0.05). Active migraine was associated with a higher expression of estrogen receptors (p = 0.04). CONCLUSIONS: Patients with active migraine had higher estrogen receptor expression, while migraine and TTH patients mainly had HER2 + BC. This association was not known earlier and could be helpful to understand deeper the relationship between BC and headache.

Association of Hashimoto's Thyroiditis and Burkitt Lymphoma: A Rare Condition to Be Considered.

We present the case of a 72-year-old woman who was diagnosed with Hashimoto's thyroiditis and who developed a low-grade fever, fatigue, and weight loss that prompted to perform a thyroid biopsy to rule out an underlying primary thyroid lymphoma. This case report offers the opportunity to review the association between Hashimoto's thyroiditis and primary thyroid lymphoma. Furthermore, it underlines the importance of considering the diagnosis of lymphoma when a thyroid mass is found in patients with an underlying Hashimoto's disease, as the timely management is essential for survival with this rare thyroid condition.

Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc-HMPAO Brain SPECT Study.

Genetic mutations of sporadic hemiplegic migraine (SHM) are mostly unknown. SHM pathophysiology relies on cortical spreading depression (CSD), which might be responsible for ischemic brain infarction. Cystic fibrosis (CF) is caused by a monogenic mutation of the chlorine transmembrane conductance regulator (CFTR), possibly altering brain excitability. We describe the case of a patient with CF, who had a migrainous stroke during an SHM attack. A 32-year-old Caucasian male was diagnosed with CF, with heterozygotic delta F508/unknown CFTR mutation. The patient experiences bouts of coughing sometimes triggering SHM attacks with visual phosphenes, aphasia, right-sided paresthesia, and hemiparesis. He had a 48-hour hemiparesis triggered by a bout of coughing with hemoptysis, loss of consciousness, and severe hypoxia-hypercapnia. MRI demonstrated transient diffusion hyperintensity in the left frontal-parietal-occipital regions resulting in a permanent infarction in the primary motor area. Later, a brain perfusion SPECT showed persistent diffuse hypoperfusion in the territories involved in diffusion-weighted imaging alteration. Migrainous infarction, depending on the co-occurrence of 2 strictly related phenomena, CSD and hypoxia, appears to be the most plausible explanation. Brain SPECT hypoperfusion suggests a more extensive permanent neuronal loss in territories affected by aura. CF may be then a risk factor for hemiplegic migraine and stroke since bouts of coughing can facilitate brain hypoxia, triggering auras.

Predictive Factors of Eribulin Activity in Metastatic Breast Cancer Patients.

OBJECTIVES: Predictive factors of response to eribulin are lacking. We aimed to investigate the activity and safety of eribulin in a real-world population of metastatic breast cancer (MBC) patients and to identify possible predictive factors of progression-free survival (PFS) and objective response. METHODS: We retrospectively analyzed 71 eribulin-treated MBC patients. Best response rate, PFS, and adverse events (AEs) were evaluated. The impact of different clinical-pathological factors on PFS was evaluated using the Cox proportional hazards model. Predictive factors of response were identified by discriminant function analysis (DFA). RESULTS: Median PFS was 3.75 months (95% CI, 2.39-4.48); 12 patients (16.90%) achieved partial response (PR), 27 (38.03%) stable disease. The most common AEs were fatigue (25.83%), neutropenia (16.56%), and peripheral neuropathy (13.91%). A worse performance status (p = 0.025) and a higher number of metastatic organ sites (p = 0.011) were associated with a worse PFS under eribulin. Overall, in the DFA-predictive model, neutrophil-to-lymphocyte ratio at baseline, estrogen receptor, Ki67, histology, and age were predictive of PR with 100% accuracy. CONCLUSIONS: Activity and safety profiles of eribulin were consistent with literature data. Performance status and number of metastatic sites were predictive factors of PFS. DFA could be a promising tool to discriminate responses to eribulin among MBC patients.

Unsupervised versus Supervised Identification of Prognostic Factors in Patients with Localized Retroperitoneal Sarcoma: A Data Clustering and Mahalanobis Distance Approach.

The aim of this report is to unveil specific prognostic factors for retroperitoneal sarcoma (RPS) patients by univariate and multivariate statistical techniques. A phase I-II study on localized RPS treated with high-dose ifosfamide and radiotherapy followed by surgery (ISG-STS 0303 protocol) demonstrated that chemo/radiotherapy was safe and increased the 3-year relapse-free survival (RFS) with respect to historical controls. Of 70 patients, twenty-six developed local, 10 distant, and 5 combined relapse. Median disease-free interval (DFI) was 29.47 months. According to a discriminant function analysis, DFI, histology, relapse pattern, and the first treatment approach at relapse had a statistically significant prognostic impact. Based on scientific literature and clinical expertise, clinicopathological data were analyzed using both a supervised and an unsupervised classification method to predict the prognosis, with similar sample sizes (66 and 65, resp., in casewise approach and 70 in mean-substitution one). This is the first attempt to predict patients' prognosis by means of multivariate statistics, and in this light, it looks noticable that (i) some clinical data have a well-defined prognostic value, (ii) the unsupervised model produced comparable results with respect to the supervised one, and (iii) the appropriate combination of both models appears fruitful and easily extensible to different clinical contexts.

Temporal-occipital glioblastoma presenting with Alice in Wonderland Syndrome in a patient with a long-time history of migraine without aura.

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder characterized by an erroneous perception of the body or the surrounding space. AIWS may be caused by different pathologies, ranging from infections to migraine. We present the case of a 54-year-old man, with a long-time history of migraine without aura, diagnosed with AIWS due to a glioblastoma located in the left temporal-occipital junction. To date, this is the first case of AIWS caused by glioblastoma. This case suggests that to exclude aura-mimic phenomena, a careful diagnostic workup should always be performed even in patients with a long-time history of migraine.