Noriko Sueoka

Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

Background Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation. Methods Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed. Results The median time to disease progression was 86 days. Of five patients, two (40%) achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades) were hypertension (60%), neuropathy (40%), and proteinuria (20%). No grade 3 toxicity was seen. No intracranial hemorrhage was observed. Conclusion We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.

Characterization of transgenic mice expressing apolipoprotein E4(C112R) and apolipoprotein E4(L28P; C112R)

Apolipoprotein E (ApoE), which is genetically polymorphic, is a constituent of different lipoproteins. Two variants, ApoE4(C112R) and ApoE4(L28P; C112R) have been linked to the risk of developing Alzheimers disease. Transgenic mice carrying ApoE4(C112R) (AD71) and ApoE4(L28P; C112R) (AD61) were generated and compared to wild-type mice. The use of glial fibrillary acidic protein as promoter led to transgene expression mainly in glial cells but also in neurons. Transgene protein levels were approximately three-and-a-half-fold that of endogenous ApoE in the glial fibrillary acidic protein-ApoE4(C112R) (AD71) and nearly twofold in the glial fibrillary acidic protein-ApoE4(L28P; C112R) (AD61) mouse lines. Neither transgenic mouse differed from wild-type in cognitive tests at the age of approximately one-and-a-half years. The locomotor activity of AD61 mice was similar to controls, whereas AD71 mice exhibited a clearly reduced level of motor activity. Immunohistological and biochemical brain protein analyses revealed no difference between strains.Thus, in the absence of morphological changes over-expression of ApoE4(C112R) on a background of endogenous mouse ApoE, may result in behavioral deficits while for the ApoE4(L28P; C112R) transgene higher expression might be required or some compensatory mechanisms might protect these animals from the behavioral abnormalities.

Development of microscopic polyangiitis in patients with chronic airway disease.

Microscopic polyangiitis (MPA) is a rare systemic vasculitis syndrome, which is often accompanied by positive myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). While pulmonary involvement of MPA consists mainly of diffuse alveolar hemorrhage and interstitial pneumonia, bronchiectasis has been reported as a pulmonary lesion in association with MPA. To investigate the clinical features of patients with MPA, focusing on the presence or the absence of preceding chronic airway diseases (CAD), we conducted a retrospective observational study of 26 patients in the last 13 years at Saga University Hospital. The clinical records and radiologic chest examinations were reviewed retrospectively. Pulmonary manifestations were alveolar hemorrhage in 3 patients (12%) and interstitial pneumonia in 5 (19%). Bronchiectasis, defined by the findings of chest radiograph and computed tomography, was found in 9 patients (35%). Four patients (15%) with bronchiectasis and one patient (4%) with chronic bronchitis had experienced chronic bronchial suppuration prior to the onset of MPA. Ten patients were classified as having chronic airway disease (CAD) before the onset of MPA. MPO-ANCA tended to be lower in the CAD group than in the non-CAD group. None of the patients in the CAD group had pulmonary hemorrhage or interstitial pneumonia. Only one patient (10%) in the CAD group died within 90 days of the onset of MPA, while 7 (43.8%) of the non-CAD group died. Our study suggests that MPA may result in part from CAD and that the clinical course of MPA with CAD may be different from MPA without CAD.

The utility of hyperthermia for local recurrence of breast cancer

BackgroundHyperthermia has long been used in combination with chemotherapy or radiation therapy for the treatment of superficial malignancies, in part due to its sensitizing capabilities. Patients who suffer from superficial recurrences of breast cancer have poor clinical outcomes. Skin metastases may particularly impair the quality of life due to the physical appearance, odor and bleeding.Case presentationA 66-year-old woman underwent mastectomy and axillary lymph node dissection for breast cancer. Nine years post-operatively, local metastases developed in the left axillary area (measuring 5 cm in diameter). Initially the tumor did not respond to radiation therapy and chemotherapy. Therefore, we added hyperthermia combined with them. Eight weeks later, the tumor became nearly flat and the patient noted improved activity in her daily life.ConclusionHyperthermia may accelerate the antitumor effects of radiation therapy and chemotherapy. This treatment provides an alternative for unresectable breast cancer skin metastases.

Five-year follow-up of treatment outcomes in patients with early-stage breast cancer and clinically negative axillary nodes treated with no lymph node dissection or axillary clearance.

BACKGROUND Sentinel lymph node biopsy has steadily replaced axillary lymph node dissection (ALND) for staging clinically node-negative breast cancer. However, ALND remains standard management of the axilla when a tumor-positive sentinel lymph node is identified. METHODS We identified 460 patients with breast cancer (clinically T1/T2N0M0) from the database for 1999-2004. Patient age ranged from 26 to 81 (median 50) years. Patients who underwent mastectomy or breast-conserving surgery with or without ALND were compared for regional recurrence, disease-free survival, and overall survival. RESULTS Patients with ALND (n = 308) were compared with the no ALND group (n = 152). Five-year overall survival and disease-free survival were not significantly different between the two groups, while there was a significant difference between them for regional recurrence. Of the 152 patients who did not undergo axillary dissection, four developed ipsilateral axillary disease, most of whom were rescued by delayed axillary dissection. Further, the criterion for identifying lymphedema was used, ie, a 2 cm circumferential change at any measured location. As a result, the incidence of lymphedema in the ALND group was 12.7%, while it was not seen in the non ALND group. CONCLUSION There is a possibility that ALND may be omitted for cT1/T2N0M0 breast cancer through a combination of hormone therapy and adjuvant chemotherapy.