TY - JOUR
T1 - Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer
AU - Gamucci, Teresa
AU - Vitale, Ilio
AU - De Maria Marchiano, Ruggero
PY - 2017
Y1 - 2017
N2 - Background: Body 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). Methods: In 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. Results: We observed a significant association between elevated levels of the two DDR biomarkers and pCR in patients with BMI<25 (p0.009 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-H2AXhighvs γ-H2AXlow: OR 10.83, 95% CI: 1.79-65.55, p=0.009). The consistency of this finding was confirmed upon internal validation. Conclusions: The 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.
AB - Background: Body 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). Methods: In 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. Results: We observed a significant association between elevated levels of the two DDR biomarkers and pCR in patients with BMI<25 (p0.009 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-H2AXhighvs γ-H2AXlow: OR 10.83, 95% CI: 1.79-65.55, p=0.009). The consistency of this finding was confirmed upon internal validation. Conclusions: The 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.
KW - Body mass index
KW - Cancer Research
KW - Chk1
KW - Double-strand breaks
KW - Genetics
KW - Oncology
KW - Pathological complete response
KW - Triple-negative breast cancer
KW - γ-H2AX
KW - Body mass index
KW - Cancer Research
KW - Chk1
KW - Double-strand breaks
KW - Genetics
KW - Oncology
KW - Pathological complete response
KW - Triple-negative breast cancer
KW - γ-H2AX
UR - http://hdl.handle.net/10807/111925
UR - http://www.biomedcentral.com/bmccancer/
U2 - 10.1186/s12885-016-3045-z
DO - 10.1186/s12885-016-3045-z
M3 - Article
SN - 1471-2407
VL - 17
SP - N/A-N/A
JO - BMC Cancer
JF - BMC Cancer
ER -