p53 status as effect modifier of the association between pre-treatment fasting glucose and breast cancer outcomes in non diabetic, HER2 positive patients treated with trastuzumab
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Patrizia Vici1,*, Francesca Sperati2, Marcello Maugeri-Saccà3, Elisa Melucci4, Anna Di Benedetto4, Luigi Di Lauro1, Laura Pizzuti1, Domenico Sergi1, Irene Terrenato2, Luca Esposito5, Carmelina Antonella Iannuzzi5, Raffaella Pasquale6, Claudio Botti7, Barbara Fuhrman8, Antonio Giordano9, Marcella Mottolese4,* and Maddalena Barba3,*
1 Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy
2 Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy
3 Division of Medical Oncology B-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy
4 Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy
5 Center for Oncologic Research of Mercogliano (CROM), Avellino, Italy
6 Oncology Research Centre of Mercogliano (CROM), G. Pascale Foundation National Cancer Institute, Naples, Italy
7 Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy
8 Department of Epidemiology, University of Arkansas for Medical Sciences, Arkansas, USA
9 Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology Temple University, Philadelphia, USA
* These authors contributed equally to this work
Maddalena Barba, email:
Antonio Giordano, email:
Keywords: p53 status, fasting glucose, HER2 positive breast cancer, trastuzumab.
Received: March 13, 2014 Accepted: June 4, 2014 Published: June 5, 2014
Mounting evidence supports the role of p53 in metabolic processes involved in breast carcinogenesis. We investigated whether p53 status affects the association of pre-treatment fasting glucose with treatment outcomes in 106 non diabetic, HER2 positive breast cancer patients treated with trastuzumab. p53 status was validated against gene sequencing of selected codons in 49 patients. The Kaplan–Meier method and log rank test were used to compare survival by categories of fasting glucose in the overall population and separate settings. Cox models included age and body mass index. Direct sequencing confirmed the lack of mutations in 73.7% of p53 negative patients and their presence in 53.3% of p53 positive cases. At 66 months, 88.3% of patients with glucose ≤ 89.0 mg/dl (median value) did not experiment disease progression compared with 70.0% in the highest category (p=0.034), with glucose being an independent predictor (p=0.046). Stratified analysis confirmed this association in p53 negative patients only (p=0.01). In the early setting, data suggested longer disease free survival in p53 negative patients in the lowest glucose category (p=0.053). In our study, p53 status acted as effect modifier of the investigated association. This may help differentiate target sub-groups and affect outcomes interpretation in similarly characterized patients.
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