Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer. Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected. With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS. TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.

Background: Identification of activated epidermal growth factor receptor ( EGFR ) mutations and application of EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs) have greatly changed the therapeutic strategies of non‐small‐cell lung cancer (NSCLC). However, the long‐term efficacy of EGFR‐TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR‐TKIs in advanced NSCLC patients with activated EGFR mutations. Methods: We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR‐TKI treatment, from April 2004 and March 2011, at the Sun Yat‐sen University Cancer Center. Several genetic alterations associated with the efficacy of EGFR‐TKIs, including the alterations in BIM , ALK , KRAS , PIK3CA , PTEN , MET , IGF1R , and ROS1 , were detected by the routine clinical technologies. The progression‐free survival (PFS) and overall survival (OS) were compared between different groups using Kaplan–Meier survival analysis with the log‐rank test. A Cox regression model was used to estimate multivariable‐adjusted hazard ratios (HRs) and their 95% confidence intervals (95% CIs) associated with the PFS and OS. Results: Among the investigated patients, 169 NSCLC patients harbored EGFR‐sensitive mutations. EGFR‐mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN ( P = 0.003 for PFS, and P = 0.034 for OS). In the combined molecular analysis of EGFR signaling pathway and resistance genes, we found that EGFR‐mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations ( P < 0.001). A Cox proportional regression model determined that PTEN deletion (HR = 4.29,95% CI = 1.72–10.70) and low PTEN expression (HR = 1.96, 95% CI = 1.22–3.13), MET FISH + (HR = 2.83,95% CI = 1.37–5.86) were independent predictors for PFS in patients with EGFR‐TKI treatment after adjustment for multiple factor. Conclusions: We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR‐TKIs.

Background: Phase II trials showed the efficacy of anti-HER2 RC48-ADC (disitamab vedotin) for HER2-positive metastatic urothelial carcinoma (UC). This study evaluated RC48 alone verses in combination with immunotherapy for locally advanced or metastatic UC using real-world data. Methods: This retrospective, multicenter, real-world study included patients with locally advanced or metastatic UC who received RC48 in five hospitals in China between July 2021 and April 2022. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results: Thirty-six patients were included. The patients were 47–87 years, and 26 (72.2%) were male. Eighteen patients received RC48 alone, and 18 received RC48 combined with a programmed death-1 antibody. The median PFS was 5.4 months. The median OS was not reached. The 6-month and 1-year PFS rates were 38.8% and 15.5%, respectively. The 1-year OS rate was 79.6%. Fourteen (38.9%) patients achieved a partial response, and the ORR was 38.9%. Eleven patients had stable disease, and the DCR was 69.4%. The median PFS for patients who received RC48 combined with immunotherapy and those who received RC48 alone was 8.5 and 5.4 months, respectively. The main treatment-related adverse events included anemia, hypoesthesia, fatigue, and elevated transaminase. No treatment-related death occurred. Conclusion: RC48 alone or combined with immunotherapy might benefit patients with locally advanced or metastatic UC, regardless of impaired renal function.

Background Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node–negative, triple‐negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes. Methods The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat‐Sen University Cancer Center. For the meta‐analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population. Results Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence‐free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta‐analysis. The meta‐analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease. Conclusions Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta‐analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.