Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity (PA) could promote weight loss/maintenance and be important determinants of breast cancer (BC) prognosis. The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes. This single-arm pre-post study, which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered to overweight and obese BC survivors shortly after treatment. Before and after the intervention, anthropometry, dietary information, quality of life (QoL) and cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were invited to participate: 42 of them started the intervention and 37 completed it. Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg, as well as significant decreases in body mass index, fat mass and waist circumference. Significant decreases in total energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %) intakes were observed while QoL and CRF showed significant increases. This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors. Assessing the long-term effects of these changes, and in particular their possible impact of BC prognosis, and designing interventions reaching a wider number of BC survivors are still issues to be addressed.

Patients with metastatic angiosarcoma undergoing chemotherapy, radiation, and/or surgery experience a median progression free survival of less than 6 months and a median overall survival of less than 12 months. Given the aggressive nature of this cancer, angiosarcoma clinical responses to chemotherapy or targeted therapeutics are generally very poor. Inhibition of beta adrenergic receptor (β-AR) signaling has recently been shown to decrease angiosarcoma tumor cell viability, abrogate tumor growth in mouse models, and decrease proliferation rates in preclinical and clinical settings. In the current study we used cell and animal tumor models to show that β-AR antagonism abrogates mitogenic signaling and reduces angiosarcoma tumor cell viability, and these molecular alterations translated into patient tumors. We demonstrated that non-selective β-AR antagonists are superior to selective β-AR antagonists at inhibiting angiosarcoma cell viability. A prospective analysis of non- selective β-AR antagonists in a single arm clinical study of metastatic angiosarcoma patients revealed that incorporation of either propranolol or carvedilol into patients' treatment regimens leads to a median progression free and overall survival of 9 and 36 months, respectively. These data suggest that incorporation of non-selective β-AR antagonists into existing therapies against metastatic angiosarcoma can enhance clinical outcomes.

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509 Background: The role of PI3Kp dysregulation as a predictor of sensitivity to PI3Kpi is unclear. We aimed to evaluate the efficacy of PI3Kpi in two cohorts of MBC pts with assessable PI3Kp status. Methods: MBC pts treated in ≥3rd line with PI3Kpi were reviewed. PI3Kp status: (a) No dysregulation: PIK3CA wt and PTEN normal; (b) PI3Kp dysregulation: PIK3CA mutation (PIK3CAmut) or PTEN low (HScore≤50). Cohort A: pts treated with single agent PI3Kpi. Cohort B: pts treated with PI3Kpi in combination with hormonal therapy (HT), chemotherapy (CT) and/or trastuzumab (T). Results: Out of 232 MBC pts screened for PI3Kp alterations from Sep09 to Sep11, 32 were treated with PI3Kpi. Cohort A (n=17): HR+/HER2- 88%, HER2+ 6%, triple negative 6%; median age 43, median MBC lines 4 (2-9); PIK3CAmut in 10/17 (58.8%; 6 exon9, 4 exon20), PTEN low 3/17 (17.6%), 1 pt both; PI3Kp dysregulation 12/17 pts. Cohort B (n=15): HR+/HER2- 40%, HER2+ 60%; median age 49, median MBC lines 4 (2-13); PIK3CAmut 3/13 assessable (23.1%; all exon20), PTEN low 6/15 (40%), 1 pt both; PI3Kp dysregulation 8/15 pts. Time to progression to PI3Kpi (TTP), overall survival from MBC diagnosis (OSMBC) and OS from PI3Kpi beginning (OSPI3Kpi), according to PIK3CA status and PI3Kp dysregulation, are shown. No differences were found according to PTEN status. Conclusions: These results suggest that the best outcomes with PI3Kpi in PIK3CAmut MBC pts occur when they are used in combination with HT/CT/T. Activity of non selective PI3Kpi used as single agents seems to be limited, making results from prospective trials with selective PI3Kα inhibitors and PI3Kpi in combinations eagerly awaited. [Table: see text]