[Effects of vinorelbine plus cisplatin as second-line neoadjuvant chemotherapy regimen in the treatment of breast cancer].

OBJECTIVE: To study the value of a combination of vinorelbine and cisplatin (NP) as second-line neoadjuvant chemotherapy regimen for primary breast cancer. METHODS: Primary breast cancer patients on neoadjuvant chemotherapy and non-responsive to anthracyclines plus taxanes received the NP regimen. The clinical objective response was evaluated with dynamic contrast-enhanced magnetic resonance imaging (MRI) according to RECIST 1.1 before operation. The pathological response was evaluated by the Miller-Payne grading system. And the toxicities were observed and evaluated according to National Cancer Institute-Common Terminology Criteria Version 3.0 (NCI-CTC v3.0). RESULTS: A total of 33 breast cancer patients were examined. The outcomes were complete remission (CR, n = 0, 0%), partial remission (PR, n = 16, 48.5%), stable disease (n = 17, 51.5%) and progressive disease (n = 0, 0%). The clinical responsive rate (CR + PR) rate was 48.5%. The pathological response rates were G1 (n = 6, 18.2%), G2 (n = 6, 18.2%), G3 (n = 10, 30.3%), G4 (n = 9, 27.2%) and G5 (n = 2, 6.1%). And the pathological response (G3+G4+G5) was found in 21 cases (63.6%). The most common toxicities included neutropenia and nausea/vomiting. No serious toxicities were observed. CONCLUSION: As a well-tolerated and effective regimen, NP regimen may be recommended as an option of second-line neoadjuvant chemotherapy regimen for primary breast cancer.

[A study on the predictive and evaluational value of molecular subtypes and dynamic contrast-enhanced magnetic resonance imaging of neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the predictive value of molecular subtypes and the evaluational value of dynamic contrast-enhanced MRI of neoadjuvant chemotherapy for breast cancer. METHODS: From January 2010 to December 2011, the 79 patients diagnosed as primary invasive breast cancer, having received 6 cycles of neoadjuvant chemotherapy and finished the mastectomy or the breast conserving surgery entered this study. A total of 79 patients participated in this prospective study. There were 6 (7.6%) luminal A cases, 42 (53.2%) luminal B cases, 14 HER-2 (17.7%) positive cases and 17 (21.5%) triple negative cases. The associations between molecular subtypes and clinical response as well as the pathological response were analyzed. The predictive value of molecular subtypes for the neoadjuvant chemotherapy was studied. RESULTS: Clinical effective rate was 85.3% (66/79). There was no statistical correlation between molecular subtypes and clinical effective rate. Pathologic effective rate was 79.7% (63/79). There was no statistical correlation between molecular subtypes and pathologic effective rate. Twenty-seven case achieved pathologic complete remission (pCR) in all the patients. No case achieved pCR in the patients classified as Luminal A. Twelve cases (28.6%, 12/42) achieved pCR in the luminal B patients.Five cases (5/14) achieved pCR in the HER-2 overexpression patients. Ten cases (10/17) achieved pCR in the triple-negative patients. There was a statistical correlation between the molecular subtypes and the pCR rate (P = 0.039), and between clinical evaluation by dynamic contrast-enhanced MRI and evaluation of pathological response (r = 0.432, P = 0.000). CONCLUSIONS: Molecular subtypes and dynamic contrast-enhanced MRI have a good value of predicting and evaluating the response of neoadjuvant chemotherapy on breast cancer.

[Factors related with pathological complete response of neoadjuvant chemotherapy in primary breast cancer].

OBJECTIVE: To assess the effect of neoadjuvant chemotherapy and the factors related with pathological complete response (pCR) of neoadjuvant chemotherapy in breast cancer. METHODS: The data of 159 primary breast cancer patients who had received neoadjuvant chemotherapy and operation with complete MRI data and histopathology evaluation in this center from January 2009 to December 2011 was analyzed. All the patients were female, aging from 28 to 70 years with a median of 50 years. The neoadjuvant chemotherapy regimens were based on anthracyclines or taxanes, and trastuzumab was used in almost half of the human epidermalgrowth factor receptor 2 positive patients. The response of neoadjuvant chemotherapy was comprehensively evaluated based on RECIST 1.1 and Miller-Payne grading system. SPSS 18.0 was used for statistical analysis. RESULTS: Among the 159 patients, 10.1% patients had achieved complete response according to the MRI evaluation, and the rate of partial response, stable disease, and progressive disease was 65.4%, 24.5%, and 0 respectively. According to the Miller-Payne grading system, 27.7% patients had pathological response evaluated as G5 (pCR), and the response evaluated as G4, G3, G2, and G1 were 28.3%, 18.9%, 12.6%, and 12.6% respectively. The higher histological grade were correlated with pCR statistically (Z = -2.820, P = 0.005). Meanwhile strong expression of Ki67 (Z = -1.989, P = 0.047) and p53 (Z = -2.457, P = 0.014) were related to pCR in a significant statistically way. CONCLUSIONS: The response of neoadjuvant chemotherapy can be predicted. The histological grade and the immunohistochemistry results of Ki67 and p53 are related to pCR of neoadjuvant chemotherapy for primary breast cancer. Basal-like breast cancer had a higher pCR statistically.

Development and external validation of a prediction model for brain metastases in patients with metastatic breast cancer.

BACKGROUND: Breast cancer patients with brain metastasis (BM) have a poor prognosis. This study aims to identify the risk factors of BM in patients with metastatic breast cancer (MBC) and establish a competing risk model for predicting the risk of brain metastases at different time points along the course of disease. METHODS: Patients with MBC admitted to the breast disease center of Peking University First Hospital from 2008 to 2019 were selected and retrospectively analyzed to establish a risk prediction model for brain metastases. Patients with MBC admitted to eight breast disease centers from 2015 to 2017 were selected for external validation of the competing risk model. The competing risk approach was used to estimate cumulative incidence. Univariate Fine-Gray competing risk regression, optimal subset regression, and LASSO Cox regression were used to screen potential predictors of brain metastases. Based on the results, a competing risk model for predicting brain metastases was established. The discrimination of the model was evaluated using AUC, Brier score, and C-index. The calibration was evaluated by the calibration curves. The model was assessed for clinical utility by decision curve analysis (DCA), as well as by comparing the cumulative incidence of brain metastases between groups with different predicted risks. RESULTS: From 2008 to 2019, a total of 327 patients with MBC in the breast disease center of Peking University First Hospital were admitted into the training set for this study. Among them, 74 (22.6%) patients developed brain metastases. From 2015 to 2017, a total of 160 patients with MBC in eight breast disease centers were admitted into the validation set for this study. Among them, 26 (16.3%) patients developed brain metastases. BMI, age, histological type, breast cancer subtype, and extracranial metastasis pattern were included in the final competing risk model for BM. The C-index of the prediction model in the validation set was 0.695, and the AUCs for predicting the risk of brain metastases within 1, 3, and 5 years were 0.674, 0.670, and 0.729, respectively. Time-dependent DCA curves demonstrated a net benefit of the prediction model with thresholds of 9-26% and 13-40% when predicting the risk of brain metastases at 1 and 3 years, respectively. Significant differences were observed in the cumulative incidence of brain metastases between groups with different predicted risks (P < 0.05 by Gray's test). CONCLUSIONS: In this study, a competing risk model for BM was innovatively established, with the multicenter data being used as an independent external validation set to confirm the predictive efficiency and universality of the model. The C-index, calibration curves, and DCA of the prediction model indicated good discrimination, calibration, and clinical utility, respectively. Considering the high risk of death in patients with metastatic breast cancer, the competing risk model of this study is more accurate in predicting the risk of brain metastases compared with the traditional Logistic and Cox regression models.

A nomogram for predicting brain metastasis in patients with de novo stage IV breast cancer.

BACKGROUND: Brain metastasis (BM) is a very serious event in patients with breast cancer. The aim of this study was to establish a nomogram to predict the risk of BM in patients with de novo stage IV breast cancer. METHODS: We gathered female patients diagnosed with de novo stage IV breast cancer between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. After randomly allocating the patients to the training set and verification set, we used univariate and multivariate logistic regression to analyze the relationship between BM and clinicopathological features. Finally, we developed a nomogram which was validated by the analysis of calibration curve and receiver operating characteristic curve. RESULTS: Of 7,154 patients with de novo stage IV breast cancer, 422 developed BM. Age, tumor size, subtype, and the degree of lung involvement were significantly correlated with BM. The nomogram had discriminatory ability with an area under curve (AUC) of 0.640 [95% confidence interval (CI): 0.607 to 0.673] in the training set, and 0.644 (95% CI: 0.595 to 0.693) in the validation set. CONCLUSIONS: Our study developed a nomogram to predict BM for de novo stage IV breast cancer, thus helping clinicians to identify patients at high-risk of BM and implement early preventive interventions to improve their prognoses.

The detection rate of methylene blue combined with another tracer in sentinel lymph node biopsy of early-stage breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Methylene blue (MB) alone or combined with 99mtechnetium-labeled sulphur colloid (Tc99m) or indocyanine green (ICG) is widely used for sentinel lymph node biopsy (SLNB) of early-stage breast cancer in developing countries and regions. However, studies investigating the effectiveness of MB combined with another tracer have produced heterogeneous results. The purpose of this network meta-analysis (NMA) was to evaluate the detection rate of MB alone, MB + Tc99m, and MB + ICG, and to examine the differences between the 3 methods. METHODS: We conducted a comprehensive electronic literature search on the PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases from inception to October 2021. The meta-analysis included 7,498 patients in 49 studies. The risk of bias for each study was independently assessed as low, moderate, or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Fixed- and random-effects models were used to calculate pooled estimates. Mixed-comparison analysis using random-effects models. We assessed statistical heterogeneity by I2 statistics and evaluated publication bias using Begg's test. RESULTS: The identification rate (IR), false-negative rate (FNR), sensitivity (SEN), and accuracy rate (AR) using MB + Tc99m were 96%, 7%, 93%, and 96%, respectively; the IR, FNR, SEN, and AR using MB + ICG were 97%, 7%, 93%, and 97%, respectively. The NMA found that IR and AR between MB + ICG and MB + Tc99m was OR =1.37 (95% CI: 0.41-4.20) and OR =1.33 (95% CI: 0.56-3.32), respectively. DISCUSSION: Our results are similar to those of most previous studies, and meta-analysis showed that the MB + Tc99m or MB + ICG mapping methods can be used to obtain higher IR and lower FNR than MB alone. Our NMA showed no statistical significance between MB + Tc99m and MB + ICG with IR and AR. Both MB + Tc99m and MB + ICG can be used as effective mapping methods in SLNB of early-stage breast cancer to improve the detection rate.

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer.

BACKGROUND: Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses. METHODS: We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves. RESULTS: Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006). CONCLUSION: Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

[Relationship between Ki67 expression and tumor response to neoadjuvant chemotherapy with anthracyclines plus taxanes in breast cancer].

OBJECTIVE: To investigate the relationship between Ki67 expression and tumor response to neoadjuvant chemotherapy with anthracyclines plus taxanes in breast cancer. METHODS: From January 2008 to June 2009, 129 patients with primary breast invasive ductal cancer received neoadjuvant chemotherapy with anthracyclines plus taxanes. The expression of Ki67 in the tumor tissues was determined by using immunohistochemistry with core needle biopsy specimens prior to the chemotherapy. The tumor response to the chemotherapy was evaluated by dynamic enhanced MRI based on RECIST2000 criteria, pathologic response was assessed according to Miller-Payne grading system, and the clinical comprehensive response was evaluated based on MRI combined with pathologic response. RESULTS: Dynamic enhanced MRI classified 87 cases (67.4%) as effective. According to the Miller-Payne grading system, 99 cases (76.7%) were ranged effective. One hundred and ten cases (85.5%) were recognized as clinically comprehensive effective. The effective rates of neoadjuvant chemotherapy in patients with a Ki67 expression >10% evaluated by the above-mentioned three standards were 73.2%, 81.4% and 89.7%, respectively; and those in patients with a Ki67 expression < or = 10% were 50.0%, 62.5% and 71.9%, respectively. Compared with patients with a Ki67 expression < or = 10%, the patients with a Ki67 expression >10% had better response rates determined by all the three standards (P values were 0.020, 0.030 and 0.010, respectively). The Ki67 expression in the tumor tissue was linearly correlated with clinically comprehensive response on the Linear-Linear association analysis. CONCLUSIONS: There is a statistic association between Ki67 expression and tumor response to the neoadjuvant chemotherapy with anthracyclines plus taxanes in breast cancer, and the patients with a higher expression of Ki67 has a better tumor response to the chemotherapy.

Intraoperative radiotherapy versus whole-breast external beam radiotherapy, and other factors associated with the prognosis of early breast cancer treated with breast-conserving surgery and radiotherapy: a retrospective study from SEER database.

BACKGROUND: This study was aimed to investigate the prognostic factors of early breast cancer treated with breast-conserving surgery (BCS) and radiotherapy. Besides, we focused our attention exclusively on the comparison of the impact on prognosis between intraoperative radiotherapy (IORT) and whole-breast external beam radiotherapy (EBRT). METHODS: An observational cohort study was performed on patients with Tis-2 N0-1 M0 breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database who treated with BCS and radiotherapy. Cox regression analysis, Kaplan-Meier analysis, and propensity score matching (PSM) were used to estimate risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: Of the 98,614 early breast cancer patients treated with BCS and radiotherapy, 97,164 (98.5%) patients underwent EBRT and 1,450 (1.5%) underwent IORT. Multivariable Cox regression analysis showed that early breast cancer patients with age ≥65, poor marital status, lack of medical insurance, histological grade III/IV (SEER 4 grades), high T stage, high N stage, and TNBC were associated with a decreased OS/BCSS, whereas ER-positive and PR-positive were associated with an improved OS/BCSS. No significant difference was observed in survival between IORT and EBRT groups (P=0.213 for OS, P=0.180 for BCSS), or between intraoperative beam radiation and intraoperative radioactive implants groups (P=0.319 for OS, P=0.972 for BCSS). CONCLUSIONS: Our study can help clinicians identify patients with poor prognosis after breast-conserving therapy. IORT may be an alternative to EBRT for early breast cancer patients who are unable to complete the long-term postoperative radiation treatment. Beam radiation and radioactive implants are both ideal alternatives for patients who choose IORT.

[Effect of neoadjuvant chemotherapy on histologic grade and expression of biological markers in breast cancer].

OBJECTIVE: The aim of this study is to investigate the changes of expression of estrogen receptors (ER), progesterone receptors (PR), Her-2, Ki-67 and histological grade after neoadjuvant chemotherapy in breast cancer. METHODS: Sixty-seven patients with histopathalogically confirmed breast cancer by core needle biopsy received neoadjuvant chemotherapy. The effect of neoadjuvant chemotherapy was assessed according to the criteria of the Japanese Breast Cancer Society: non-effective (G1), mildly effective (G2), moderately effective (G3), markedly effective (G4) and completely effective (G5). All pathological slides were retrospectively reviewed. Immunohistochemical staining (EnVision method) was used to detect the expression of ER and PR, Her-2 and Ki-67. The pre- and post-neoadjuvant chemotherapy status of tumor histological grade, ER and PR, Her-2 and Ki-67 expression in the 49 cases were compared. RESULTS: The effect of neoadjuvant chemotherapy was assessed in 67 patients. There were 5 cases (7.5%) in G1, 19 in G2 (28.4%), 20 in G3 (29.9%), 17 in G4 (25.4%) and 6 in G5 (9.0%), respectively. PR positive rate was 71.4% after chemotherapy versus 91.8% before chemotherapy, with a statistically significant reduction (P = 0.021). However, the ER and Her-2 expression before and after neoadjuvant chemotherapy was stable. Of the patients with invasive ductal carcinoma, 28.6% had histological grade change after neoadjuvant chemotherapy, and 85.7% of patients decreased one grade. The proportion of histological grade change in the G1, G2, G3, G4 were 0, 5.9%, 41.2% and 54.5%, respectively (P = 0.013). The average rate of Ki-67 expression decreased from 28.3% pre-chemotherapy to 11.0% post-chemotherapy (P = 0.011). After the neoadjuvant chemotherapy, the Ki-67 expression rate decreased by > 10%, > 20%, > 30%, > 40% and > 50% in 3 groups (G1 and G2, group G3, group G4 and G5) showed a tendency to be increased, with a significant difference (P < 0.05). CONCLUSION: PR expression in breast cancer decreases after neoadjuvant chemotherapy, while ER and Her-2 expressions remain stable. After neoadjuvant chemotherapy, the histological grade and proliferation index are decreased and correlated with the response to chemotherapy. Therefore, histological grade and proliferation index may be effective complementary factors in assessment of the effectiveness of neoadjuvant chemotherapy.

[Effects and toxicity of neoadjuvant chemotherapy with vinorelbine and cisplatin in treatment of operable breast cancer previously non-responsive to anthracyclines and taxanes-containing regimen: analysis of 19 cases].

OBJECTIVE: To evaluate the short-term effects and toxicity of vinorelbine combined with cisplatin (NP) as a neoadjuvant chemotherapy regimen in treatment of operable breast cancer non-responsive to the combination of anthracyclines and taxanes. METHODS: Nineteen breast cancer patients, all female, who failed to achieve complete remission (CR) or partial remission (PR) to the combination of anthracyclines and taxanes as neoadjuvant regimen were treated with 2 cycles of NP regimen (vinorelbine 25 mg/m(2), on days 1 and 8 and cisplatin 70 mg/m(2), on days 1 and 3, both by intravenous infusion, as a cycle). The clinical objective response was evaluated with dynamic contrast-enhanced MRI of the breast before operation and the pathological response was evaluated by pathological examination. The toxicity of the NP regimen was evaluated according to National Cancer Institute-Common Toxicity Criteria v.3.0. RESULTS: The CR + PR rate of the NP regime was 52.6% (10/19), and pathological response (G(2) + G(3) + G(4) + G(5)) was found in 17 cases (89.5%, 17/19). The most common toxicities were neutropenia and nausea/vomiting. These toxicities were reversible and did not cause death. CONCLUSION: A well-tolerated and effective regimen for breast cancer patient who fail to respond to the combination of anthracyclines and taxanes neoadjuvant chemotherapy, the NP regimen can be considered as an effective choice of second-line regimen. It can be considered as an effective choice of second-line regimen.

[Prospective study on the role of MRI and B ultrasonography in evaluating the tumor response to neoadjuvant chemotherapy in breast cancer].

OBJECTIVE: To evaluate the role of breast B ultrasonography and magnetic resonance imaging in assessing the tumor response to neoadjuvant chemotherapy in breast cancer. METHODS: Eighty-five patients with breast cancer diagnosed by core needle biopsy received neoadjuvant chemotherapy entered this prospective study. Breast B ultrasonography and dynamic enhanced MRI was performed before chemotherapy induction, after the second course and the fourth course of chemotherapy prior to the surgery. Clinical evaluation was made through the tumor reduction measured by B ultrasonography and MRI, based on the response evaluation criteria in solid tumors (RECIST). RESULTS: Measured by dynamic enhanced MRI, 56 patients got partial response (PR), 27 got stable disease (SD) and 2 got progressive disease (PD), none complete response (CR). Measured by B ultrasonography, 52 patients got PR, 31 got SD, 2 got PD, no CR. Residual tumor size after chemotherapy on MRI correlated well with post-operative pathologic findings (r = 0.783, P < 0.05), and B ultrasonography correlated moderately with microscopic findings (r = 0.576, P < 0.001). CONCLUSION: Dynamic enhanced MRI is a reliable method to evaluate tumor response to neoadjuvant chemotherapy in breast cancer.

Clinicopathologic analysis of 722 breast cancer patients who met the inclusion criteria of the TAILORx trial.

BACKGROUND: The results of the Trial Assigning IndividuaLized Options for Treatment (TAILORx) suggested that approximately 70% of T1-2N0M0, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients can avoid chemotherapy and receive only adjuvant endocrine therapy. We conducted a retrospective analysis of the clinicopathologic features and prognostic factors of patients with breast cancer who met the inclusion criteria of the TAILORx trial. METHODS: According to the enrollment criteria of the TAILORx trial, a retrospective analysis was performed on patients with breast cancer who were treated from January 2008 to December 2015 at Peking University First Hospital. The clinicopathologic characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. RESULTS: A total of 2430 patients with early stage breast cancer who were admitted at our hospital had complete clinicopathologic data and follow-up information. Of these patients, 722 met the inclusion criteria and were enrolled in the present study, accounting for 29.7% of all patients. Among them, 417 (57.8%) patients received only adjuvant endocrine therapy (the non-chemo group), and 305 (42.2%) patients received adjuvant chemotherapy followed by adjuvant endocrine therapy (the chemo group). No statistically significant difference was observed in overall survival (OS) between the two groups (non-chemo vs. chemo: 5-year OS: 97.9% vs. 97.9%, χ = 1.00, P = 0.995; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.46-2.21). A significant difference was observed in disease-free survival (DFS) between the two groups (non-chemo vs. chemo: 5-year DFS: 97.9% vs. 94.7%, χ = 8.65, P = 0.003; HR = 3.05, 95% CI: 1.40-6.67). The choice of adjuvant therapy was associated with clinicopathologic factors, such as the age at diagnosis, T stage, histologic grade, the Ki67 index, the presence of intravascular tumor thrombus (P < 0.001), pathologic type, and menstrual status (P = 0.014). CONCLUSIONS: In the absence of internationally recognized multigene testing methods, for patients with early hormone receptor-positive, HER2-negative breast cancer, clinicians can develop a treatment plan based on clinicopathologic features only, which can effectively screen some patients who do not need adjuvant chemotherapy. However, nearly half of patients still receive adjuvant chemotherapy, and whether these patients can be exempted from chemotherapy warrants further exploration.

A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

BACKGROUND: Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. METHODS: We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. RESULTS: This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant differences in either 5-year DFS (χ2 = 0.440, P= 0.507) or 5-year OS (χ2 = 1.530, P= 0.216). CONCLUSIONS: The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.

[Role of tissue factor in the invasion of cultured human colon carcinoma cells and its correlation with matrix metalloproteinases].

OBJECTIVE: To investigate the role of tissue factor expression in the invasive ability of human colon carcinoma cells and to analyze the correlation between tissue factor and MMP-2 and MMP-9. METHODS: HT-29 cells with sense-TFcDNA transfection and LoVo cells with antisense-TFcDNA transfection were implanted subcutaneously into nude mice as well as controls. The expressions of MMP-9 and MMP-2 at the protein and mRNA levels were detected by Western blot and RT-PCR respectively; Gelatin zymography was used for assay of the MMP-9 and MMP-2 activities in the supernatant cultured media of LoVo cells with antisense-TFcDNA transfection and controls. RESULTS: The expressions of MMP-9 and MMP-2 at the protein and mRNA levels in the group of HT-29 cells with sense-TFcDNA were significantly increased with untransfected HT-29 cells. The expression in the group of LoVo cells with antisense-TFcDNA had a significant decrease than that of the controls. The MMP-9 and MMP-2 activities of LoVo cells with antisense-TFcDNA were weakened because of the lower expression of tissue factor by gelatin zymography. The expression of MMP-9 and MMP-2 were closely correlated to the expression of tissue factor. CONCLUSION: Tissue factor can increase the invasive ability of human colon carcinoma cells. The partial mechanism is that TF can upregulate the expressions of MMP-9 and MMP-2. Tissue factor may be an inner agonist in the secretion of MMPs in colon carcinoma cells.

[The role of tissue factor expression in the invasive and metastatic ability of colorectal carcinoma].

OBJECTIVE: To investigate the role of tissue factor (TF) expression in the invasive and metastatic ability of colorectal carcinoma and explore the influence of TF on the invasive ability of HT-29 cells. METHODS: TF expression of specimens from 85 colorectal carcinomas and 6 colorectal adenomas was observed by immunohistochemistry. The role of TF expression in prognosis and tumor invasion and metastasis was analyzed. The plasmids pcDNA3.1/Zeo bearing either sense or antisense-TFcDNA were transfected into HT-29 cells by the way of Lipofectamine 2000. TF proteins in transfected and untransfected HT-29cells were detected by Western blot. In vitro Matrigel invasion assays were performed to show the invasive ability of those cells. RESULTS: TF expression was positive in 40 (47.1%) of 85 colorectal carcinoma specimens, but negative in normal mucosa and adenoma specimens. TF expression showed significant correlation with tumor invasive depth (r = 0.895, P < 0.01). TF expression showed significant correlation with synchronous and metachronous hepatic metastasis (r = 0.974, P < 0.01 and r = 0.963, P < 0.01 respectively). TF expression was a significant risk factor for hepatic metastasis (P < 0.01) and prognosis (P < 0.01). TF expression in HT-29 cells with sense/antisense-TFcDNA transfection was more/less than that of the cells without transfection. The invasive ability of HT-29 cells with sense-TFcDNA transfection was increased in vitro compared with the untransfected cells, but HT-29 cells with antisense-TFcDNA transfection got the contrary change. CONCLUSIONS: TF may take part in the invasive and metastatic process of primary colorectal carcinoma, and TF expression may be an indicator of hepatic metastasis and prognosis for colorectal carcinoma patients. TF expression may increase the invasive ability of HT-29 cell in vitro.

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

OBJECTIVE: This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. METHODS: Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. RESULTS: TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. CONCLUSION: TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Clinicopathological classification and individualized treatment of breast cancer.

BACKGROUND: The clinicopathological classification was proposed in the St. Gallen Consensus Report 2011. We conducted a retrospective analysis of breast cancer subtypes, tumor-nodal-metastatic (TNM) staging, and histopathological grade to investigate the value of these parameters in the treatment strategies of invasive breast cancer. METHODS: A retrospective analysis of breast cancer subtypes, TNM staging, and histopathological grading of 213 cases has been performed by the methods recommended in the St. Gallen International Expert Consensus Report 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 213 tumor samples have been investigated by immunohistochemistry according to methods for classifying breast cancer subtypes proposed in the St. Gallen Consensus Report 2011. RESULTS: The luminal A subtype was found in 53 patients (24.9%), the luminal B subtype was found in 112 patients (52.6%), the HER2-positive subtype was found in 22 patients (10.3%), and the triple-negative subtype was found in 26 patients (12%). Histopathological grade and TNM staging differed significantly among the four subtypes of breast cancer (P < 0.001). CONCLUSION: It is important to consider TNM staging and histopathological grading in the treatment strategies of breast cancer based on the current clinicopathological classification methods.