Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers.

BACKGROUND: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. PATIENTS AND METHODS: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. RESULTS: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. CONCLUSIONS: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

[Gallbladder metastasis from breast carcinoma: a new case report]. / Métastase vésiculaire d'un carcinome mammaire: une nouvelle observation.

The breast carcinoma metastases preferentially in the axillary lymph nodes, bones, lungs, liver and soft tissues. Gastrointestinal or bladder dissemination is very rare. We report the case of a 63-year-old female with a clinical presentation of acute cholecystitis, who underwent laparoscopic cholecystectomy in emergency. The gallbladder showed a nodule at the infundibulum, which was responsible for the gallbladder hydrops with macroscopic features of a cholangiocarcinoma. Histological examination disclosed a metastasis from a lobular breast carcinoma with positive hormone receptors, but no overexpression of the Neu oncogene. Immunohistochemistry showed positive staining for cytokeratin7 suggesting a lesion of breast origin. The absence of E-cadherin was consistent with lobular carcinoma while negative CA 19.9 excluded cholangiocarcinoma. The patient had received 15 years previously a right mastectomy with axillary dissection followed by chemotherapy and radiotherapy for breast carcinoma of ductal type labeled SBR stage III, pT3N1 M0, showing hormone receptors but absent Neu oncogene. Proofreading of the mastectomy histological slide concluded that it was a lobular rather than a ductal type carcinoma, confirming the finding of a gallbladder metastasis 15 years after the mastectomy. The patient showed no local recurrence or contralateral lesions on magnetic resonance imaging (MRI). The bone scan showed metastases in the skull, scapula, right rib cage, thoracolumbar spine and pelvis, also confirmed by MRI. A treatment with exemestane and zoledronic acid was introduced. The follow-up at 6 months showed regression of the bone lesions and absence of parenchymal new locations.