Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Prognosis in very young women with triple-negative breast cancer: retrospective study of 216 cases.

The aim of this investigation was to compare clinical pathological characteristics and prognosis of very young and older triple-negative breast cancer (TNBC) patients in order to assess their relevance to TNBC in an younger population. Data of TNBC patients diagnosed between 2002 and 2007 were retrospectively analyzed by computer based chart information. Baseline tumor characteristics, biological markers, and patients' prognosis were compared between very young (≤ 35 years) and older (>35 years) TNBC patients. In the 216 cases of operable TNBC patients, 48 (22.2%) were ≤ 35 years and 168 (77.8%) were >35 years. Very young TNBC patients had showed a high clinical stage, more positive lymph nodes, Ck5/6 and/or EGFR expression (P = 0.049, 0.006, and 0.011, respectively). Compared to older TNBC patients, very young TNBC patients have short disease-free survival (P = 0.031), while no significant difference was found in overall survival (OS) (P = 0.075). In multivariate analysis, lymph node metastatic status was a significant predictor of OS. TNBC of very young patients is an aggressive breast cancer subtype, but the overall survival of both young and older TNBC patients did not have significant differences.

CD147, MMP9 expression and clinical significance of basal-like breast cancer.

Our objective is to investigate the expression of CD147 and metallo-proteinase 9 (MMP9) in patients with basal-like breast cancer (BLBC) so as to determine whether these two genes may be correlated with prognosis of BLBC. We examined the expression of the CD147 and MMP9 in BLBC by immunohistochemistry. Furthermore, we analyzed the correlation between BLBC and several factors related to tumor progression, along with the prognostic value of BLBC. BLBC was significantly associated with CD147 and MMP9 expression (P = 0.000), and prone to lymph node metastasis and distant metastasis. Patients with BLBC showed shorter disease-free survival (P = 0.005) and overall survival (OS) (P = 0.011). In univariate analysis, CD147, MMP9, lymph node metastasis and clinical stage are independent prognostic factors affecting OS. In multivariate analysis, only clinical stage was identified as an independent prognostic factor. Patients with BLBC have a high expression of CD147 and MMP9; BLBC is correlated with a poor prognosis.

Clinical significance of basal-like breast cancer in Chinese women in Heilongjiang province.

BACKGROUND: Our objective was to clarify the clinical and biological characteristics of basal-like breast cancer (BLBC) and non-basal-like breast cancer (TN3BKE) in Heilongjiang. METHODS: We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) and B cell specific moloney murine leukemia virus integration site 1( Bmi-1) in triple-negative breast cancer (TNBC). We studied the correlation between BLBC and several factors related to tumor progression, along with its prognostic value. RESULTS: In the 229 cases of operable TNBC, BLBC was detected in 178 (77.7%) and TN3BKE- in 51 (22.2%). There was no significant difference in clinicopathological factors between them, However, BLBC was significantly associated with Bmi-1 expression (P=0.000) and shorter disease-free survival (DFS) (P = 0.045) and overall survival (OS) (P=0.041). CONCLUSIONS: Compared with the non-basal group, patients with BLBC have a high expression of Bmi-1 and a poor prognosis.

[Inhibitory effect of KAI1 gene on breast cancer cell growth in vitro].

OBJECTIVE: To explore the inhibitory effect of KAI1 gene on breast cancer cell growth in vitro. METHODS: Highly metastatic human breast cancer cell line MDA-MB-231 was transfected with pCMV-KAI1 or mock transfected plasmid pCMV with lipofectamine. Western blot was used to determine the expression of target protein of KAI1. The proliferative ability of cells was tested by MTT assay and colony-forming test. The cell cycle pattern was assayed by flow cytometry. The metastatic ability was investigated by cell adhesion and invasion assays. RESULTS: A stable cell clone transfected with KAI1 gene was obtained and over-expression of KAI1 protein was observed. There was a significant decline in cell proliferative ability of pCMV-KAI1 transfected MDA-MB-231 cells in comparison with the mock-transfected ones and non-transfected ones, revealed by MTT assay and colony-forming test (P < 0.05). The ability of adherence and invasion of pCMV-KAI1 transfected cells was significantly reduced in comparison with the other two groups (P < 0.05). Also, flow cytometry analysis revealed that in KAI1 transfected cell group the number of cells in G0/G1 phase increased markedly from 36.78% +/- 0.61% to 64.00% +/- 7.56%, while the number of cells in G2/M phase decreased from 17.88% +/- 0.76% to 7.63% +/- 0.60%, comparing with the non-transfected ones. CONCLUSION: KAI1 gene suppresses the invasive ability of human breast cancer cells in vitro and may inhibit the proliferative ability by changing the cell cycle pattern.