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 (Î³-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 Î³-H2AX and pChk1, respectively), but not in their heavier counterpart. Results regarding Î³-H2AX were confirmed in uni- and multivariate models and, again, for leaner patients only (Î³-H2AXhighvs Î³-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 Î³-H2AX varies according to BMI status. Indeed, elevated levels of Î³-H2AX seemed associated with lower pCR rate only in leaner patients, whereas differences in pCR rate according to Î³-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.
- Body mass index
- Cancer Research
- Double-strand breaks
- Pathological complete response
- Triple-negative breast cancer