Yidong Zhou

This study aimed to evaluate the efficacy and safety of adjuvant chemotherapy with pirarubicin plus capecitabine (AX regimen) in Chinese node-negative breast cancer (BCa) patients. Two hundred eighty Chinese pT1-2N0M0 BCa patients under 70 years of age were equally and randomly assigned to receive four cycles of adjuvant therapy with the AX regimen or pirarubicin and cyclophosphamide (AC regimen) between January 2010 and May 2011. End points included overall survival (OS), disease-free survival (DFS), chemotherapy-induced toxicities, and quality of life (QoL). The 4-year DFS (AX vs. AC, 93.6 vs. 92.9 %, P = 0.761) and OS (97.1 vs. 96.4 %, P = 0.965) were similar between the two treatment arms. The AX group, compared to the AC group, experienced significantly less frequent grade III/IV vomiting (11.4 vs. 26.4 %, P < 0.001), whereas the incidence of other grade III/IV chemotherapy-associated toxicities was comparable between the two groups (all P values >0.05). Use of the AX regimen was associated with significantly higher QoL scores in the domains of physical, role, and social functions than the AC regimen (P values 0.05). In comparison with the AC regimen, AX adjuvant chemotherapy is equally beneficial for node-negative BCa patients younger than 70 years with respect to OS and DFS. The AX regimen is primarily advantageous over the AC regimen based on less frequent severe toxicities and better health-related QoL.

The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear. 147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated. ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman’s rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2^{-△△C T} value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001). The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.