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The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I–III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years. [ABSTRACT FROM AUTHOR]

Simple Summary: This study provides information about the genetic alterations associated with disease recurrence in early stage HER2-positive breast cancer. We found seven upregulated and two downregulated differentially expressed genes in patients with recurrence. In addition, the tumor inflammation signature score and the scores of six immune-related breast cancer signatures were decreased in patients with recurrence. Our study offers insight into the underlying genetic background of recurrence risk and can help to develop effective risk-adapted therapeutic strategies in early stage HER2-positive breast cancer. We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies' nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA, and germline APOBEC3A/B deletion polymorphism in patients with breast cancers and to investigate the correlation between their expressions and clinicopathological characteristics. Methods: RNA and DNA samples were extracted from 138 breast cancer tissues and adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using quantitative real-time polymerase chain reaction. Insertion and deletion PCR assays were performed to detect the A3B deletion allele. The serum concentrations of soluble programmed death-ligand 1 (sPD-L1) and interferon gamma were determined using enzyme-linked immunosorbent assays. Results: A3B mRNA expression levels were significantly higher in triple-negative breast cancers compared to hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers. Older age of the patient and high ki-67 expression were associated with increased expression levels of A3A and A3B mRNA. Advanced tumor stage, presence of lymph node involvement, and high histological grade were associated with increased expression levels of A3A mRNA. The APOBEC3A/B deletion allele was found in 77 (55.8%) patients. TP53 and PIK3CA mutations were detected in 62 (44.9%) and 31 (22.5%) patients, respectively. The presence of a PIK3CA mutation was associated with lower A3A mRNA expression levels. There was a weak positive relationship between A3A mRNA expression levels and serum sPD-L1 levels. Conclusions: There was a difference in A3B mRNA expression levels according to breast cancer subtypes, and high levels of A3A and A3B mRNA expressions were associated with an aggressive phenotype. There was a high incidence of APOBEC3A/B deletion allele. Further studies are needed to identify the clinical significance of APOBEC in Asian patients with breast cancer. [ABSTRACT FROM AUTHOR]