Metformin: a modulator of bevacizumab activity in cancer? A case report.

Recurrent type I endometrial cancer ((EC)) has poor prognosis and demands novel therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody, has shown clinical activity in this setting. To our knowledge, however, although some diabetic cancer patients treated with bevacizumab may also take metformin, whether metformin modulates response to anti-VEGF therapy has not yet been investigated. Here, we report the case of a patient with advanced (EC) treated, among other drugs, with bevacizumab in combination with metformin. The patient affected by relapsed (EC) G3 type 1, presented in march 2010 with liver, lungs and mediastinic metastases. After six cycles of paclitaxel and cisplatin she underwent partial response. Later on, she had disease progression notwithstanding administration of multiple lines of chemotherapy. In march 2013, due to brain metastases with coma, she began steroid therapy with development of secondary diabetes. At this time, administration of Bevacizumab plus Metformin improved her performance status. CT scans performed in this time window showed reduced radiologic density of the lung and mediastinic lesions and of liver disease, suggestive of increased tumor necrosis. Strong F-18-FDG uptake by PET imaging along with high levels of monocarboxylate transporter 4 and lack of liver kinase B1 expression in liver metastasis, highlighted metabolic features previously associated with response to anti-VEGF therapy and phenformin in preclinical models. However, clinical benefit was transitory and was followed by rapid and fatal disease progression. These findingsalbeit limited to a single casesuggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab. As metformin is widely used among diabetes patients as well as in ongoing clinical trials in cancer patients, these results deserve further clinical investigation

Familial breast cancer: characteristics and outcome of BRCA 1–2 positive and negative cases

BACKGROUND: The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1–2 mutation are poorly known. METHODS: From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. RESULTS: BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40% – p = 0.002 at univariate analysis, not significant at multivariate analysis) and negative estrogen receptors (43% vs 29%). Treatment was not different in the two groups. In the 86 BRCA-WT patients, the first event was a local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and distant metastases in 16 (19%). In the 39 BRCA positive patients, the corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in event free survival, with a median of 180 months in both groups of patients. At 20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA-WT, but this difference was not statistically significant. CONCLUSION: Although BRCA positive patients have more frequently negative prognostic factors, their prognosis appears to be equal to or better than in patients with BRCA-WT

Prospective study of outcomes in Sporadic versus hereditary breast cancer (POSH): study protocol

Background: young women presenting with breast cancer are more likely to have a genetic predisposition to the disease than breast cancer patients in general. A genetic predisposition is known to increase the risk of new primary breast (and other) cancers. It is unclear from the literature whether genetic status should be taken into consideration when planning adjuvant treatment in a young woman presenting with a first primary breast cancer. The primary aim of the POSH study is to establish whether genetic status influences the prognosis of primary breast cancer independently of known prognostic factors. Methods/design: the study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period. Discussion: power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforwar

Sertoli cell tumor: a rare case in an elderly patient

Eur J Gynaecol Oncol. 2006;27(1):86-7. Sertoli cell tumor: a rare case in an elderly patient. Nicoletto MO, Caltarossa E, Donach M, Nardelli GB, Parenti A, Ambrosini A. SourceDepartment of Medical Oncology, Padua Hospital, Padova, Italy. Abstract Sertoli-Leydig cell tumors constitute < 1% of ovarian tumors, mostly in young women with virilization; however, not all present endocrine manifestations. A 72-year-old female presented with an abdominal mass and no signs of virilization. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and selective pelvic lymphadenectomy was performed. The pathologic diagnosis was poorly-differentiated sex cord-stromal tumor with Sertoli cells. No adjuvant chemotherapy or radiation was administered. At 12-month follow-up the patient showed no evidence of disease

Combined use of urinary UGP and serum CA 125 in the diagnosis of gynecological cancers.

UGP, the beta-core fragment of human chorionic gonadotropin has been proposed as a tumor marker for gynecological malignancies. This fragment may be detected in a single morning-specimen of urine using an enzyme immunoassay. In this study, the diagnostic usefulness of urine UGP and serum CA 125 measurement for gynecological neoplasias (149 cases) was evaluated using a control group of patients with benign gynecological diseases (69 cases) and healthy females (99 cases). Considering the neoplastic patients in comparison to patients with benign diseases, the best diagnostic efficiency (78%) was found to correspond to a cut-off level of 120 pmol/mol creatinine the sensitivity being 73% and the specificity 90%. With this cut-off, an efficiency of 82% for healthy controls was obtained. Since the menopausal condition increases UGP levels, and though no significant difference for UGP was found between healthy subjects and patients with benign diseases, we decided to consider the reference populations as a single group. Thus, we evaluated the UGP performance on the basis of menopausal status. When a specificity of 95% was fixed, the cut-off values were 120 and 180 pmol/mol creatinine for pre- and postmenopausal women respectively, the sensitivity being 73% and 64%. Finally the combined evaluation of UGP and CA 125 improved their individual clinical efficiency for the diagnosis of ovarian serous cystadenocarcinomas, assuring a sensitivity of 86% and a specificity of 89%

Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.

INTRODUCTION: Malignant pleural effusion (MPE) is a frequent complication in many types of tumors diminishing the patient's ability to perform activities. Despite various studies on talc treatment, some doubts about its safety and effectiveness remain, so the search for a more ideal intrapleural agent continues. We analyzed the effectiveness and safety of intrapleural paclitaxel in ovarian and breast cancer patients. PATIENTS AND METHODS: The primary endpoint was overall response rate (ORR); secondary objectives included time to progression (TTP), overall survival (OS) and safety of intrapleural paclitaxel. Pharmacokinetics of the drug was also analyzed. After drainage of pleural effusion and lung re-expansion, paclitaxel 120 mg/m(2) diluted in normal saline was infused through a preinserted catheter which was immediately closed and reopened 24 h later. Blood and pleural fluid samples were collected 1, 4 and 24 h after the end of paclitaxel instillation. When MPE was less than 200 ml/24 h the catheter was removed. Chest radiographs were performed at the beginning of intrapleural paclitaxel, at 1 and 2 months later or with clinical deterioration. RESULTS: We enrolled 18 patients with recurrent MPE: 11 with ovarian cancer and 7 with breast cancer. ORR was 77.8% at 1 month and 88.8%. at 2 months. Median TTP was 5.5 months (CI 95% 0.9-10.1) and median OS was 8.9 months (CI 95% 0.1-17.6). Patients achieving a complete response obtained a statistically significant longer survival than did patients with partial response or progressive disease. Chest pain, fever, and dyspnea were the most frequent side effects. Intrapleural paclitaxel concentrations were very high (mean ± SD = 478 ± 187 mg/l) and declined slowly (mean 24 h reduction ~30%). Detectable but low taxol plasma levels were found in most patients (mean ± SD = 0.045 ± 0.073 mg/l). CONCLUSION: Intrapleural paclitaxel is a safe and effective palliative treatment for MPE from breast and ovarian cancers and may be integrated with systemic chemotherapy