Objective To summarize the research progress of distributional heterogeneity of the molecular pathology characteristics in breast cancer. Methods The related literatures about the distribution of the molecular pathology characteristics in breast cancer were reviewed. Results The breast cancer had the same heterogeneity as other cancers. At the same time, the molecular pathology characteristics, such as estrogen receptor (ER), progesterone receptor (PR), Ki-67, and human epidermal growth factor receptor-2 (HER-2), had the distributional heterogeneity. The distributional heterogeneity of molecular pathology characteristics in breast cancer could effect the pathologic diagnosis, the treatment, and the prognosis. Conclusion Although there are some new techniques which were used to investigate the heterogeneity of breast cancer, but each way has some problems. The more attention should be paid to the research about the distributional heterogeneity of the molecular pathology characteristics in breast cancer.
ObjectiveTo compare the clinicopathological characteristics and prognosis of young early breast cancer patients with different human epidermal growth factor receptor 2 (HER2) expression levels, and to analyze the clinicopathological characteristics and prognosis of young early breast cancer patients with low HER2 expression. MethodsA total of 1 723 breast cancer patients who were treated in the Department of Breast Surgery of the First Affiliated Hospital of Xi’an Jiaotong University between June 2016 and June 2018 were collected and divided into three groups: HER2-negative, low-expression, and high-expression. The clinicopathological characteristics of the three groups were compared, and the relationship between HER2 expression and patients’ prognosis was analyzed. ResultsThere were 512 HER2-negative patients, 748 HER2-low expression patients, and 463 HER2-high expression patients. The results of the clinical pathological characteristics analysis of the three groups of patients showed that there were no statistical differences in marital status, menopausal status, family history, single T stage (tumor size), single M stage (distant metastasis), affected side, vascular tumor thrombus, and radiotherapy in the three groups of breast cancer patients with different HER2 expression levels (P>0.05). However, there were statistical differences in age, Ki-67 expression level, N stage, TNM stage, surgical method, estrogen receptor and progesterone receptor status, histological type, histological grade, whether to receive neoadjuvant therapy and adjuvant chemotherapy in breast cancer patients with different HER2 expression levels (P<0.05). The results of survival analysis showed that the prognosis of early breast cancer patients may not be significantly correlated with the HER2 expression level, and the prognosis of young early breast cancer patients may also not be statistically correlated with the HER2 expression status. ConclusionsBreast cancer patients with different HER2 expression levels differ in multiple clinicopathological characteristics, but these differences do not significantly affect the prognosis of the patients. Especially for early-stage breast cancer, HER2 expression levels do not seem to have a significant impact on prognosis. This suggests that HER2 status may not be a decisive factor in treatment and prognosis assessment, and other pathological characteristics and treatment methods need to be considered comprehensively. The prognosis of young breast cancer patients in early stage may also not be statistically correlated with HER2 expression status.
ObjectiveTo systematically evaluate the correlation of amplification of human epidermal growth factor receptor 2 (HER2) with the clinicopathological characteristics and prognosis of colorectal cancer patients.MethodsPubMed, EMbase, Cochrane Library, Chinese Biomedical Literature Database (CBM), Wanfang, and other databases were searched, and cohort studies focused on the relationship between HER2 amplification and clinicopathological characteristics and prognosis of colorectal cancer patients were included. The retrieval time limit was from October 2020, and RevMan 5.4 software was used for meta-analysis.ResultsA total of 9 studies (11 cohorts) were included for meta-analysis of 7 209 patients with colorectal cancer. Results of the meta-analysis showed that HER2 amplification was not associated with overall survival [HR=1.10, 95%CI (0.98, 1.24), P=0.11]. HER2 amplification was not correlated with gender [OR=0.98, 95%C1 (0.74, 1.31), P=0.90] and tumor differentiation [OR=0.80, 95%C1 (0.49, 1.32), P=0.39], but correlated with the tumor location [OR=1.85, 95%C1 (1.01, 3.37), P=0.04], RAS wild-type gene [OR=6.36, 95%C1 (3.41, 11.87), P<0.000 01], TNM stage [OR=0.45, 95%C1 (0.32, 0.64), P<0.000 01], lymph node metastasis [OR=1.54, 95%C1 (1.12, 2.13), P=0.008], and the depth of tumor invasion [OR=0.17, 95%C1 (0.05, 0.55), P=0.003].ConclusionCurrent evidence shows that HER2 amplification is not associated with OS in patients with colorectal cancer, but associated with tumor infiltration, lymph node metastasis, TNM stage, tumor site, and RAS genotype.
Objective To investigate the differences in clinicopathological characteristics and prognostic survival of human epidermal growth factor receptor 2 (HER2) high expression, HER2 low expression and HER2 negative breast cancer. MethodWe retrospectively collected 1 560 female breast cancer patients who underwent surgical treatment at the Department of Breast and Thyroid Surgery in Renmin Hospital of Wuhan University between January 8, 2010 and December 31, 2015, and divided them into high expression group, low expression group and negative group according to HER2 expression, to compare the differences in clinicopathological characteristics among the three groups of breast cancer patients and to explore the factors influencing prognosis. Results The proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, TNM stage Ⅲ, Ki67 high expression, and hormone receptor negative expression were higher in the high expression group than those in the low expression group and negative group (P<0.050); the proportions of histological grade Ⅲ, tumor diameter >2 cm, lymph node metastasis, and TNM stage Ⅲ were higher in the low expression group than those in the negative group (P<0.050). However, the proportions of Ki67 high expression and hormone receptor negative expression were lower than those of the negative group (P<0.050). The 5-year disease-free survival rate were 85.6%, 80.3% and 74.5% for the high expression, low expression and negative group, respectively, and the 5-year overall survival rate were 90.4%, 86.0% and 80.7%, respectively. The results of multivariate Cox proportional hazard model showed that patients with high histological grade, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year disease-free survival (P<0.050); patients with older age, high histological grade, lymph node metastasis, late TNM stage, Ki67 high expression and weaker HER2 expression intensity had worse 5-year overall survival (P<0.050). Conclusions The intensity of HER2 expression affects the 5-year disease-free survival and overall survival of breast cancer patients, and the higher the intensity of HER2 expression, the better the 5-year disease-free survival and overall survival, while the weaker the HER2 expression, the worse the 5-year disease-free survival and overall survival.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To investigate the relationship between the expressions of P-gp, GST-π and C-erbB-2 and clinicopathologic characteristics as well as prognosis in breast cancer. Methods The expressions of P-gp， GST-π and C-erbB-2 were detected by immunohistochemistry in 48 cases of breast cancer, and histopathologic characteristics as well as 5-year survival rate of these cases were analyzed. Results There was no significant difference in the expressions of P-gp and GST-π with age, histologic grade, number of lymph node metastasis and TNM stage of breast cancer ( P ＞ 0.05). There was significant difference in expression of C-erbB-2 with histologic grade, number of lymph node metastasis and TNM stage of breast cancer （ P ＜ 0.05）. Positive rate of P-gp expression in breast cancer with positive C-erbB-2 expression was remarkably higher than that in breast cancer with negative C-erbB-2 expression ( P ＜ 0.05) . Positive rate of GST-π and C-erbB-2 expression in survivals within 5 years was remarkably lower than that in deaths within 5 years ( P ＜ 0.01). Conclusion P-gp participates primary drug-resistance mechanism of breast cancer. The possibility of primary drug-resistance is higher in breast cancer with positive C-erbB-2 expression. The expression of C-erbB-2 helps to evaluate prognosis and the result of treatment in breast cancer.
Objective Investigate the effect and treatment prospects of urokinase-type plasminogen activator receptor（uPAR）in human epidermal growth factor receptor-2 （HER-2） positive breast cancer. Method Aricals related effect of uPAR in HER-2 positive breast caner were retrieved through Pubmed， and the role of uPAR was reviewed. Results uPAR played a very important role in the HER-2 positive breast cancer， anti-uPAR monomer or uPAR binding inhibitors could inhibit the growth， invasion and metastasis of breast cancer cells. Conclusion uPAR is one of the effective target for breast cancer， and it provides a new breakthrough in the treatment of HER-2 positive breast cancer.
ObjectiveTo analyze the clinicopathologic characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with different expression status of estrogen receptor (ER). MethodsThe patients with HER2-negative breast cancer met the inclusion and exclusion criteria and were treated in the Affiliated Hospital of Southwest Medical University from January 1, 2017 to December 31, 2019 were retrospectively collected, and then were assigned into 3 groups according to the ER expression status: ER-negative (ER expression positive rate <1%) group, ER-low expression (ER expression positive rate 1%–10%) group, and ER expression positive rate >10% group. The differences of clinicopathologic characteristics, therapy, and prognosis among the 3 groups were compared. And the risk factors affecting recurrence and metastasis of patients with ER-low expression were analyzed by Cox proportional hazards regression model. ResultsA total of 610 patients with HER2-negative breast cancer were included in this study, including 130 patients in the ER-negative group, 48 patients in the ER-low expression group, and 432 patients in the ER expression positive rate >10% group. The Bonferroni method was used to correct the test level after pairwise comparison, it was found that the histological grade was later (P<0.001, P=0.023) and the Ki-67 expression was higher (P<0.001, P=0.023) in the ER-negative group and ER-low expression group as compared with the ER expression positive rate >10% group; The proportion of the patients receiving chemotherapy in the ER-negative group was higher than that of the ER expression positive rate >10% group (χ2=10.310, P=0.001), while which had no statistical difference between the ER-low expression group and the ER-negative group or the ER expression positive rate >10% group (Fisher exact probability method, P=1.000; χ2= 3.585, P=0.058); The proportion of patients receiving endocrine therapy in the ER-low expression group was higher than that in the ER-negative group (χ2=36.333, P<0.001) and lower than the ER expression positive rate >10% group (χ2=246.996, P<0.001). The difference in disease-free survival (DFS) curves among 3 groups was statistically significant (χ2=46.805, P<0.001); There were no statistical differences in the overall survival (OS) curve and DFS curve between the ER-negative group and the ER-low expression group (Two stage test, P=0.786; χ2=1.141, P=0.286), and which in the ER expression positive rate >10% group were significantly better than thoses in the ER-negative group (χ2=10.137, P=0.001; χ2=39.344, P<0.001) and the ER-low expression group (χ2=4.075, P=0.044; χ2=31.911, P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that N1 and N2 [N0 as reference: RR (95%CI)=7.740 (1.939, 30.897), P=0.004; RR (95%CI)=9.513 (1.990, 45.478), P=0.005) and T3 [T1 as reference: RR (95%CI)=27.357 (2.188, 342.041), P=0.010] increased the probabilities of recurrence and metastasis HER2-negative breast cancer patients with ER-low expression. ConclusionsAccording to results of this study, patients with HER2-negative breast cancer showed certain differences in histological grade and Ki-67 expression among patients with three different ER expression status, but no statistical difference is found between ER-low expression and ER-negative breast cancer, and the prognoses of both are worse than that of ER expression positive rate >10% breast cancer patients. Lymph node metastasis and larger tumor are risk factors affecting recurrence and metastasis in ER-low expression breast cancer patients.
MicroRNA (miRNA) is a noncoding RNA and protein involved in regulating gene expression in the transcription level. Epidermal growth factor receptor (EGFR) is a protein tyrosine kinase receptor and its mutations have been confirmed in non-small cell lung cancer (NSCLC) by a large number of studies in recent years. EGFR tyrosine kinase inhibitor (EGFR-TKI) is widely used for treatment of NSCLC patients with EGFR mutation. In recent years, miRNA is more and more important in tumor metastasis. The role of EGFR mutations in NSCLC has become a hot spot as well. New researches report that the relationship between miRNA and EGFR mutations plays an important role in NSCLC metastasis. Therefore, we write this review to discuss the mechanisms of miRNA and EGFR mutations in metastasis of NSCLC.
Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.