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

Patrizia Vici, Francesca Sperati, Marcello Maugeri-Saccà, Elisa Melucci, Anna Di Benedetto, Luigi Di Lauro, Laura Pizzuti, Domenico Sergi, Irene Terrenato, Luca Esposito, Carmelina Antonella Iannuzzi, Raffaella Pasquale, Claudio Botti, Barbara Fuhrman, Antonio Giordano, Marcella Mottolese, Maddalena Barba

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)10382-10392
Number of pages11
JournalOncotarget
Volume5
Issue number21
Publication statusPublished - 2014

Keywords

  • Fasting glucose
  • HER2 positive breast cancer
  • p53 status
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this