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Claudia Omarini,1 Patrizia Palumbo,2 Annarita Pecchi,3 Stefano Draisci,3 Sara Balduzzi,4 Cecilia Nasso,1 Monica Barbolini,1 Chrystel Isca,1 Alessandro Bocconi,1 Luca Moscetti,1 Silvia Galetti,5 Giovanni Tazzioli,6 Pietro Torricelli,3 Stefano Cascinu,1 Federico Piacentini1 1Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy; 2Division of Clinical Nutrition and Metabolism, Department of Specialist Medicines, University Hospital of Modena, Modena, Italy; 3Department of Radiology, University Hospital of Modena, Modena, Italy; 4Statistics Unit, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy; 5Division of Clinical Nutrition and Metabolism, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy; 6Department of General Surgery and Surgical Specialities, University Hospital of Modena, Modena, ItalyCorrespondence: Claudia OmariniDivision of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Via Del Pozzo 71, Modena 41122, ItalyTel +39 059 4222845Email claudia.omarini@gmail.comBackground: Fat tissue is strongly involved in BC tumorigenesis inducing insulin resistance, chronic inflammation and hormonal changes. Computed tomography (CT) imaging instead of body mass index (BMI) gives a reliable measure of skeletal muscle mass and body fat distribution. The impact of body composition parameters (BCPs) on chemosensitivity is still debated. We examined the associations between BCPs and tumor response to neoadjuvant chemotherapy (NC) in patients treated for operable breast cancer (BC).Methods: A retrospective review of BC patients treated with NC in Modena Cancer Center between 2005 and 2017 was performed. BCPs, such as subcutaneous fat area (SFA), visceral fat area (VFA), lumbar skeletal muscle index (LSMI) and liver-to-spleen (L/S) ratio were calculated by Advance workstation (General Electric), software ADW server 3.2 or 4.7. BMI and BCPs were correlated with pathological complete response (pCR) and survival outcomes.Results: 407 patients were included in the study: 55% with BMI < 25 and 45% with BMI ≥ 25. 137 of them had pre-treatment CT scan imagines. Overweight was significantly associated with postmenopausal status and older age. Hormonal receptor positive BC was more frequent in overweight patients (p

Background.Everolimus has been shown to overcome endocrine resistance in hormone receptor positive advanced breast cancer patients. Predictive biomarkers of everolimus efficacy have been investigated in primary breast cancer tissue without finding univocal results. The goal of this study was to investigate the mutational burden in the metastatic site of endocrine-resistant tumors treated with everolimus plus exemestane.Patients and Methods.Mass Array Sequenom platform was used to analyse genetic status of 18 cancer-related genes in 25 archival tumor specimens from metastatic lesions and available primary matched breast cancer tissue of patients treated with everolimus and exemestane for advanced disease. An exploratory analysis of everolimus efficacy in terms of progression free survival benefit and single gene mutation was carried out.Results. The overall detection rate of mutation was 30% and 38% from metastatic and primary breast cancer samples, respectively.AKT1E17Kwas the most frequent mutated gene. No primary breast cancer and matched relapse maintained the same mutation profile. Considering molecular pathways, the most of the genes belong to PI3K pathway (AKT1E17K,PI3KCAE545K, andKITG565R,S709F). In patients with detected mutations in breast and/or recurrence tissue the median PFS was 5,6 months while in the subgroup of patients with no mutations the median PFS was 7,5 months.Conclusions. The mutational status of breast cancer recurrence allows the identification of some genes potentially correlating tumor response/resistance to everolimus. The most frequently mutated genes were involved in the PI3K/AKT/mTOR pathway highlighting that the deregulation of this pathway in the relapse plays a crucial role in the mechanisms of everolimus resistance/sensitivity. Owing to the small sample size and the retrospective nature of the study, these correlations need to be validated in a large prospective study.