title: 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.
abstract: 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.
authors: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors: Patrizia
authors: P
authors: Vici
authors: Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors: Francesca
authors: F
authors: Sperati
authors: Division of Medical Oncology B-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors: Marcello
authors: M
authors: Maugeri-Saccà
authors: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Elisa
authors: E
authors: Melucci
authors: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Anna
authors: A
authors: Di Benedetto
authors: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors: Luigi
authors: L
authors: Di Lauro
authors: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors: Laura
authors: L
authors: Pizzuti
authors: Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy.
authors: Domenico
authors: D
authors: Sergi
authors: Biostatistics-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors: Irene
authors: I
authors: Terrenato
authors: Center for Oncologic Research of Mercogliano (CROM), Avellino, Italy.
authors: Luca
authors: L
authors: Esposito
authors: Center for Oncologic Research of Mercogliano (CROM), Avellino, Italy.
authors: Carmelina Antonella
authors: CA
authors: Iannuzzi
authors: Oncology Research Centre of Mercogliano (CROM), G. Pascale Foundation National Cancer Institute, Naples, Italy.
authors: Raffaella
authors: R
authors: Pasquale
authors: Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors: Claudio
authors: C
authors: Botti
authors: Department of Epidemiology, University of Arkansas for Medical Sciences, Arkansas, USA.
authors: Barbara
authors: B
authors: Fuhrman
authors: Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology Temple University, Philadelphia, USA.
authors: Antonio
authors: A
authors: Giordano
authors: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors: Marcella
authors: M
authors: Mottolese
authors: Division of Medical Oncology B-Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors: Maddalena
authors: M
authors: Barba
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001786:Blood Glucose / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D015987:Effect Modifier, Epidemiologic; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001786:Blood Glucose; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53; C508053:ERBB2 protein, human