BackgroundPatients who achieve a tumor pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better outcomes than patients with residual tumor. However, tumors still recur in the pCR patients. Therefore, we aim to explore factors associated with tumor recurrence in this patient population.MethodsA total of 1,913 patients diagnosed with breast cancer between 1995 and 2020 and received NAC were included in this analysis. Clinicopathological data of the patients were retrospectively collected. We used Cox regression analysis to assess the associations of clinicopathological factors with patients’ outcome. Proteomic study of tumors was applied to identify differentially expressed proteins (DEPs) between tumors from the pCR patients with tumor recurrence and tumors from those without tumor recurrence. PPI network analysis of the corresponding genes of DEPs was used to identify the hub genes. The prognostic value of the corresponding genes of DEPs was evaluated using two online databases, Kaplan-Meier Plotter and bc-GenExMiner. The genes that were significantly associated with patients’ survival in both databases, as well as being identified as hub genes, were considered as potential prognostic markers for pCR patients. Publicly available data from Gene Expression Omnibus (GEO) was used to verify the prognostic value of the identified marker.ResultsAmong the 1,913 included patients, 420 had tumor pCR. The median follow-up for the pCR patients was 32.6 months (IQR, 16.3-55.5). Overall estimated 5-year risk of tumor recurrence for the pCR patients was 11%. Multivariable analysis showed that a higher pre-NAC clinical T stage and N stage were independent predictors for increased risk of tumor recurrence (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.01-6.51, P=0.047 for clinical T stage and HR 3.48, 95%CI 1.37-8.83, P=0.009 for clinical N stage). NAC regimens, the type of breast and axillary surgery, and adjuvant chemotherapy were not associated with tumor recurrence. Finally, aldehyde dehydrogenase (ALDH) 3A2 was identified by the proteomic study and was verified as a potential predictor for tumor recurrence in the pCR patients (with a median follow up of 3.78 years for dataset GSE32603 and 2.74 years for dataset GSE25066 from GEO, tumor recurrence rate: low versus high expression, 20.7% versus 4.5% [data from GSE32603]; 10.9% versus 0% [data from GSE25066]).ConclusionsClinical T stage, clinical N stage and tumor expression of ALDH3A2 were potential markers for predicting tumor recurrence in the pCR patients after NAC.
Background: Despite patients with breast cancer who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) generally demonstrate improved survival, some of these patients will develop breast cancer recurrence. Identification of factors associated with recurrence in patients with pCR after NAC would be helpful to optimize treatment strategies in breast cancer. In this study, we aim to particularly explore the factors associated with the prognosis of this patient population.Methods: Data of patients from three tertiary hospitals and treated with NAC between 2005 and 2019 were retrospectively collected. A pCR was defined as no invasive tumor in the breast and no tumor in the lymph node (ypT0/is, ypN0). Factors associated with pCR were analyzed using univariable and multivariable logistic regression analyses. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The prognostic value of clinicopathological factors regarding DFS and OS were determined by univariable and multivariable Cox regression analyses.Results: A total of 897 patients were used for the analysis, including 287 patients with a pCR and 610 patients without pCR. Clinical TNM stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, Ki67, molecular subtype, NAC regimen and NAC cycles were associated with pCR status, with TNM stage and molecular subtype as independent predictors of pCR. Patients with a pCR had a superior DFS (pCR vs non-pCR, hazard ratio [HR] 0.26 (95% confidence interval [CI] 0.15-0.45, P<0.001) and OS (pCR vs non-pCR, hazard ratio [HR] 0.13 (95% confidence interval [CI] 0.05-0.35, P<0.001). In patients with pCR, clinical T stage, N stage and TNM stage were associated with DFS and OS, with higher N stage as an independent predictor of a worse DFS and OS.Conclusions:Clinical N stage of breast cancer is an independent predictor of worse DFS and OS in patients with a pCR after NAC. Possible this could support treatment escalation in this patient population in the future. Citation Format: Li-Yun Xie, Kun Wang, Yan-Xia Shi, Hai-Lu Chen, Jian-Hao Huang, Yang-Hang Fan, Si-Qi Qiu, Zhi-Yong Wu. Higher clinical lymph node stage predicts worse survival in patients with breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-53.
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