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.
目的 研究乳腺癌患者雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）表达情况及免疫组织化学分子亚型分布。 方法 对2003年1月－2008年9月四川大学华西医院病理科3 365例乳腺癌病理报告存档资料进行激素受体（ER/PR）、HER-2表达情况及免疫组织化学分子亚型分布进行分析。 结果 3 365例确诊的乳腺癌患者中，ER阳性1 824例（54.2%），PR阳性1 841例（54.7%），HER-2过表达284例（8.4%）。相关分析显示ER与PR表达呈正相关（P＜0.001），HER-2与ER、PR表达均呈负相关（P＜0.001）。免疫组织化学分子亚型结果显示luminal A型最常见，为1 993例（59.2%）；basal-like型为623例（18.5%）；HER-2过表达型为169例（5.0%）；luminal B型最少，为115例（3.4%）；未分类的为465例（13.8%）。 结论 乳腺癌患者激素受体及HER-2表达有特殊性，激素受体阳性率＞50%，HER-2阳性率在不同研究中显示出不同的结果，尚需进一步研究；ER、PR与HER-2具有良好的相关性；免疫组织化学分子亚型中luminal A型最常见。
ObjectiveTo summarize the progress in mechanisms of resistance to trastuzumab in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MethodsBy searching Pubmed and CNKI, the literatures of mechanisms of resistance to trastuzumab in treating HER2-positive breast cancer were reviewed. ResultsThe possible mechanism of resistance to trastuzumab are thought to include HER2 gene amplification and high protein expression; impaired access of trastuzumab to HER2; bidirectional crosstalk between ER and HER2; HER2 downstream signal transduction pathway activation; expansion expression of other RTKs and membrane-associated receptors; alterations in apoptosis and cell cycle control as well as multi-gene mutation, etc. ConclusionsMechanisms of trastuzumab resistance in HER2-positive breast cancer is complicated, a better understanding will be achieved by comprehensive analysis of existing possible mechanisms. The outcome of HER2-positive breast cancer patients who developed resistance to trastuzumab will be improved by appropriate multi-target regime.
ObjectiveTo explore the correlation between the texture features of gastric cancer plain CT images and the expression of HER2.MethodsA retrospective collection the datas of 62 patients with gastric cancer who underwent CT scans of the upper abdomen and (or) the whole abdomen from January 2017 to January 2021 in Leshan City People’s Hospital. The treatment method was surgery. The HER2 expression of gastric cancer tissue was detected after the operation. There were 45 male patients and 17 female patients. Lauren classification: 18 cases of intestinal type, 30 cases of diffuse type, and 14 cases of mixed type. Fifty-two cases were HER2 expression negative [age: (63.54±10.32) years], and 10 cases were HER2 expression positive [age: (61.70±11.70) years]. The MaZda module in the MaZda 4.6 version software was used to perform the image normalization, interest area delineation, texture feature extraction, and texture feature selection on the CT plain scan image, and perform texture feature discrimination and misjudgment rate analysis in the B11 module.ResultsThere was no correlation between HER2 expression and age, gender of patients and Lauren classification of tumors (P>0.05). The analysis methods of nonlinear discriminant analysis (NDA)/artificial neural network (ANN), linear discriminant analysis (LDA)/1-nearest-neighbor (1-NN), principal component analysis (PCA)/1-NN, and raw-data analysis (RDA)/1-NN can better correspond to the CT plain scan texture feature parameters of gastric cancer and the expression level of HER2.ConclusionsTexture analysis based on CT plain images has the potential to non-invasively detect the HER2 expression in gastric cancer. The best comprehensive performance texture discrimination method is NDA/ANN and LDA/1-NN.
ObjectiveTo analyze the clinicopathologic features and prognosis of breast cancer patients with low human epidermal growth factor receptor-2 (HER2) expression. MethodsThe breast cancer patients underwent initially surgical resection in the First Hospital of Shanxi Medical University from October 2015 to October 2017 and met the criterion of this study were retrospectively gathered. Based on the immunohistochemical / in situ hybridization detection results, the patients were divided into three subtypes of HER2 zero, low, and positive expressions, and the differences in the clinicopathologic characteristics, overall survival (OS) and disease-free survival (DFS) of the three subtypes of breast cancer patients were compared. At the same time, the risk factors affecting the OS and DFS of breast cancer patients with low HER2 expression were analyzed. ResultsA total of 315 eligible patients were gathered in this study, including 68 patients with HER2 zero expression, 121 patients with low HER2 expression, and 126 patients with positive HER2 expression. There were no statistic differences in the menstrual status, T stage, and histological classification between the breast cancer patients with low HER2 and positive HER2 expressions (P>0.05), but the proportions of the patients with lymph node metastasis, histological grade Ⅲ, negative hormone receptor (HR) and high Ki67 expression in the low HER2 expression patients were lower than those in the positive HER2 expression patients. And compared with HER2 zero expression breast cancer patients, the proportions of premenopausal / perimenopausal, T2–4, N1–3, histological grade Ⅱ, ductal carcinoma, negative HR, and low Ki67 expression patients in the breast cancer patients with low HER2 expression were higher (P<0.05). While the survival curves of OS and DFS by Kaplan-Meier method had no statistic differences among the three subtypes of the breast cancer patients (χ2=0.070, P=0.966; χ2=0.362, P=0.835). The multivariate analysis results by Cox proportional hazards regression found that the low HER2 expression breast cancer patients with histological grade Ⅲ and negative HR had the higher risks of OS and DFS shortening (P<0.05). In addition, the risk of DFS shortening in the patients with T stage 2–4 and N stage 1–3 was increased (P<0.05). ConclusionsFrom the results of this study, breast cancer patients with low HER2 expression is different from the other two subtypes of breast cancer in terms of clinicopathologic characteristics. However, there are no statistical significances in comparing the OS and DFS of three types of breast cancer patients, but it is found that histological grading and HR are related to the OS and DFS of breast cancer patients with low HER2 expression, and it is also found that T stage and N stage are related to the DFS of breast cancer patients with low HER2 expression, so more attentions should be paid to the treatment plans.
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.
ObjectiveTo investigate the influencing factors of total pathological complete response (tpCR) in newly treated human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients after neoadjuvant targeted chemotherapy, so as to provide more reference for the formulation of surgical plan and prognosis assessment. MethodsNinety-five newly treated HER2-positive breast cancer patients after neoadjuvant targeted chemotherapy were retrospectively chosen in the period from January 2021 to January 2023 in our hospital and all patients were divided into tpCR group (51 cases) and non-tpCR group (44 cases) according to whether tpCR was achieved after neoadjuvant targeted chemotherapy or not. Univariate and multivariate methods were used to evaluate the independent influencing factors of tpCR after neoadjuvant targeted chemotherapy in newly treated HER2-positive breast cancer patients. The prediction model based on the above independent influencing factors was constructed and the potential predictive efficacy of this model for tpCR after neoadjuvant targeted chemotherapy was evaluated. ResultsAmong 95 patients, 51 patients achieved tpCR after neoadjuvant targeted chemotherapy and 44 patients did not achieve tpCR. The results of the multivariate logistic regression model analysis showed that the patients with HER2 3+(OR=6.102, P=0.014), HER2+/hormone receptor– (HER2+/hormone receptor+ OR=0.129, P=0.006), and trastuzumab+pantomizumab treatment (OR=6.582, P=0.014) had higher tpCR rate, estrogen receptor 3+ (OR=0.122, P=0.0.033), progesterone receptor 3+ (OR=0.179, P=0.020), Ki-67 index of 15%–30% (OR=0.088, P=0.030) and 31%–60% (OR=0.066, P=0.017) had lower tpCR rate. The predicted area under the curve of this model was 0.881 [95%CI (0.815, 0.947)]. ConclusionsThe achievement of tpCR after new adjuvant treatment in newly diagnosed HER2 positive breast cancer patients is related to the expression level of HER2 in immunohistochemistry, molecular typing and new adjuvant targeted treatment scheme. At the same time, the prediction model based on these influencing factors can predict the effect of tpCR after new adjuvant treatment in patients to a certain extent.
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.