Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer

BMC Cancer

Research Article

Irene Terrenato¹  Francesca Sperati¹  Clara Natoli²  Laura Iezzi²  Marcella Mottolese³  Anna Di Benedetto³  Cristiana Ercolani³  Claudio Botti⁴  Laura Pizzuti⁵  Domenico Sergi⁵  Luigi Di Lauro⁵  Patrizia Vici⁵  Marcello Maugeri-Saccà⁶  Maddalena Barba⁶  Ruggero De Maria⁷  Lucia Mentuccia⁸  Teresa Gamucci⁸  Ilio Vitale⁹ 

[1] Biostatistics-Scientific Direction, “Regina Elena” National Cancer Institute, Rome, Italy;Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, Chieti, Italy;Department of Pathology, “Regina Elena” National Cancer Institute, Rome, Italy;Department of Surgery, “Regina Elena” National Cancer Institute, Rome, Italy;Division of Medical Oncology 2, “Regina Elena” National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy;Division of Medical Oncology 2, “Regina Elena” National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy;Scientific Direction, “Regina Elena” National Cancer Institute, Rome, Italy;Institute of General Pathology, Catholic University of the Sacred Heart, Largo Agostino Gemelli, 10, 00168, Rome, Italy;Medical Oncology Unit, ASL Frosinone, Frosinone, Italy;Scientific Direction, “Regina Elena” National Cancer Institute, Rome, Italy;Department of Biology, University of Rome “Tor Vergata”, Rome, Italy;

关键词: Body mass index;    γ-H2AX;    Chk1;    Double-strand breaks;    Pathological complete response;    Triple-negative breast cancer;   

DOI  :  10.1186/s12885-016-3045-z

 received in 2015-11-13, accepted in 2016-12-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBody mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT).MethodsIn this retrospective analysis 54 TNBC patients treated with NACT were included. The relationship between DDR biomarkers, namely phosphorylated H2A Histone Family Member X (γ-H2AX) and phosphorylated checkpoint kinase 1 (pChk1), and pCR was reconsidered in light of BMI data. The Pearson’s Chi-squared test of independence (2-tailed) and the Fisher Exact test were employed to assess the relationship between clinical-molecular variables and pCR. Uni- and multivariate logistic regression models were used to identify variables impacting pCR. Internal validation was carried out.ResultsWe observed a significant association between elevated levels of the two DDR biomarkers and pCR in patients with BMI < 25 (p = 0.009 and p = 0.022 for γ-H2AX and pChk1, respectively), but not in their heavier counterpart. Results regarding γ-H2AX were confirmed in uni- and multivariate models and, again, for leaner patients only (γ-H2AXhigh vs γ-H2AXlow: OR 10.83, 95% CI: 1.79–65.55, p = 0.009). The consistency of this finding was confirmed upon internal validation.ConclusionsThe predictive significance of γ-H2AX varies according to BMI status. Indeed, elevated levels of γ-H2AX seemed associated with lower pCR rate only in leaner patients, whereas differences in pCR rate according to γ-H2AX levels were not appreciable in heavier patients. Larger investigations are warranted concerning the potential role of BMI as effect modifier of the relationship between DDR-related biomarkers and clinical outcomes in TNBC.

【 授权许可】

CC BY   
© The Author(s). 2017