Predictive and prognostic effect of HO-1 expression in breast cancer patients undergoing neoadjuvant chemotherapy

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Abstract
Purpose Heme oxygenase-1 (HO-1) has complex biological function, and is a candidate oncogene with a wide variety of deleterious functions in breast cancer. Here, we evaluated the relationship between expression of HO-1 protein with clinical response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Methods We used immunohistochemistry (IHC) to determine expression of HO-1 protein from core needle biopsy before NAC, then applied univariate and multivariate analyses to understand the relationship between HO-1 with pathological complete response (pCR) outcomes. Next, Kaplan–Meier and Log-rank tests were used to compare disease-free survival (DFS) and overall survival (OS), between groups, and Cox proportional hazards regression analysis applied for prognostic evaluation. Results A total of 575 patients with locally advanced invasive breast cancer were included in the study, of which 111 (19.3%) achieved pCR after NAC. Results from multivariate analysis showed that high HO-1 expression was an independent predictor of low pCR rate (OR 0.254, 95% CI 0.026–0.643, p = 0.002). Moreover, results from survival analysis showed that high HO-1 expression was significantly associated with shorter DFS (HR 4.843, 95% CI 1.205–32.572, p = 0.026), but not with OS (HR 3.219, 95% CI 0.928–32.124, p = 0.071). Furthermore, HO-1 expression was significantly associated with lower pCR rate (OR 0.102, 95% CI 0.013–0.352), p = 0.001), poor DFS (HR 8.562, 95% CI 1.592–34.950, p = 0.009), and OS (HR 7.835, 95% CI 1.220–56.213, p = 0.023) of patients with triple-negative breast cancer (TNBC) patients. Conclusion Our results indicated that HO-1 expression is not only a biomarker for predicting pCR, but also a prognostic factor in breast cancer patients in a neoadjuvant setting, especially in TNBC subgroups.
Funding Information
  • National Natural Science Foundation of China (82160481)
  • Natural Science Foundation of Guangxi Province (2017GXNSFAA198088, 2019GXNSFAA245067)
  • the Youth Program of Scientific Research Foundation of Guangxi Medical University Cancer Hospital (2021-05)

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