[Evaluation and indication of human epithelial growth factor receptor 2 status in breast carcinoma with amplified chromosome].

OBJECTIVE: To study the evaluation of human epithelial growth factor receptor 2 (HER2) status in breast carcinoma with amplified chromosome 17 centromere locus (CEP17) and clinical significance of CEP17 amplification. METHODS: Two hundred-eighteen cases of breast carcinoma were collected. We performed immunohistochemistry (IHC) to test HER2 protein and fluorescence in situ hybridization (FISH) to evaluate HER2 gene status. RESULTS: Two cases in this cohort manifested CEP17 amplification. HER2 signals for case 1 was countable, and the average number was 2.6 per one nuclei, and the signals of CEP17 were clustered or multipunctiform. This case was evaluated as no HER2 amplification, but with amplified CEP17 . In case 2 the signals of HER2 and CEP17 were countable, and the average number of HER2 signal was 6.8 per one nucleus while CEP17 signal was 5.9 per one nucleus. The status was considered as HER2 and CEP17 coamplification. And the levels of HER2 protein expression of these two cases were both two plus. CONCLUSION: The incidence of CEP17 amplification in breast carcinoma is rare, with or without HER2 amplification. We recommend to evaluate the exact HER2 status by the HER2 copy number, and should also analyze the HER2/CEP17 ratio and the level of HER2 protein, for providing more accurate evidence to support the clinical target therapy.

[Clinical application of sentinel lymph node biopsy under the guidance of contrast-enhanced ultrasound plus methylene blue in patients with breast cancer].

OBJECTIVE: To explore the application feasibility of contrast-enhanced ultrasound (CEUS) plus methylene blue in sentinel lymph node biopsy (SLNB) for breast cancer and determine the ultrasonographic features of sentinel lymph node (SLN). METHODS: The microbubbles of SonoVue were injected subcutaneously and intradermally into tumor side of areola. The images were observed to record the size, number, lymphatic door, aspect ratio, enhanced time and enhanced mode of SLN. Methylene blue was injected into SLN under the guidance of ultrasound. The marked SLNs were dissected for pathological examinations. Based upon the results, the specimens were divided into SLN metastasis and SLN non-metastasis groups. RESULTS: A total of 34 breast cancer patients were recruited. Among them, SLN was detected preoperatively in 31 patients by CEUS and the rate was 91.2%. And the postoperative results showed that 14 were confirmed positive (metastasis group) and 17 negative (non-metastasis group). The sensitivity, specificity, accuracy and false negative rate of CEUS for detecting SLNs were 93.3% (14/15), 100% (16/16), 96.8% (30/31) and 6.7% (1/15) respectively. The model of stepwise regression analysis showed that lymphatic door, aspect ratio and enhanced mode were helpful to differentiate SLN metastasis and SLN non-metastasis groups. CONCLUSIONS: SLNB under the guidance of CEUS plus methylene blue offer prompt and accurate localization with a lower cost. It may enhance the detection rate of SLNB in breast cancer.

[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.

[Analysis of intraoperative molecular assessment of sentinel lymph nodes in breast carcinoma].

OBJECTIVE: To evaluate the reliability and application of GeneSearch(TM) breast lymph node assay (Genesearch), a real-time fluorescence quatitative PCR method, in intraoperative assay of metastasis in sentinel lymph nodes (SLNs) from breast cancer patients. METHODS: Totally 140 SLNs from 80 patients with breast carcinoma were prospectively studied from May 2010 to August 2010. The 80 patients included 78 women and 2 men who ranged in age from 29 to 85 years, and the median age is 49 years. The expression of CK19 and mammaglobulin in all 140 SLNs were detected by Genesearch, and the results were compared with that of histological evaluation of both frozen and paraffin-embedded sections. RESULTS: Among SLNs, by histological analyses, there were 121 without metastasis, 17 with macrometastasis, 2 with micrometastasis, and none of isolated tumor cell. By Genesearch, there were 119 without metastasis and 21 with metastasis. Genesearch showed sensitivity of 89.4%, positive predictive value of 81.0%, negative predictive value of 98.3% and specificity of 96.7% by comparing to histological analyses. The concordance between Genesearch and histological analysis was 95.7%. The sensitivity of Genesearch was 15/17 for macrometastasis and 2/2 for micrometastasis. CONCLUSIONS: Genesearch detection presents high sensitivity and specificity in evaluating metastasis of sentinel lymph nodes in breast cancer, but strict performance technically is necessary to avoid false positive and false negative results. Inability of further subtyping for the positive cases might be the key limitations for wide application of this method.

[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.

[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.

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 prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving patients' persistence to adjuvant aromatase inhibitor medication for postmenopausal, early stage breast cancer.

Since the rate of persistence to adjuvant endocrine therapy such as 5-year aromatase inhibitors (AI) would decrease over time in patients with hormone-sensitive breast cancer, it is necessary to investigate if a patient support program could modify patients' beliefs and improve their persistence to AI treatment. This was a prospective, multicenter, controlled, observational study to evaluate the efficacy of a patient support program in improving postmenopausal patients' persistence to adjuvant AI medication for early stage breast cancer (NCT00769080). The primary objective was to compare the rates of 1-year persistence to upfront adjuvant AI for patients in the two observational arms (standard treatment group and standard treatment plus patient support program group). In this study, 262 patients were enrolled in the standard treatment group and 241 patients in the standard treatment plus patient support program group. The mean 1-year persistence rates were 95.9 and 95.8% for the standard treatment group and the standard treatment plus patient support program group, respectively (P=0.95). The mean times to treatment discontinuation were 231.2 days in the standard treatment group and 227.8 days in the standard treatment plus patient support program group, with no statistically significant difference between the two groups (P=0.96). There was also no statistically significant difference in the reason for treatment discontinuation (P=0.32). There was a significant relationship between the patient centered care questionnaire and poor persistence (odds ratio=3.9; 95% CI, 1.1-13.7; P=0.035), suggesting that the persistence rate of patients with whom the doctor always or usually spends time is greater than that of patients with whom the doctor sometimes or never spends time. Patients' persistence to adjuvant AI medication for postmenopausal, early stage breast cancer is relatively high in the first year and is not significantly increased by adding a patient support program to standard treatment.

[Relationship between the response of breast cancer to neoadjuvant chemotherapy and PI3K/mTOR pathway].

OBJECTIVE: To explore the relationship between the status of PI3K/mTOR pathway and the therapeutic efficacies of neoadjuvant chemotherapy for breast cancer. METHODS: A total of 105 patients receiving 4-6 cycles of taxane-based neoadjuvant chemotherapy at our centre between January 2009 and November 2010 were recruited into this retrospective study. The expressions of PTEN, p-AKT (Ser473) and p-mTOR (Ser2448) were detected by immunohistochemistry before neoadjuvant chemotherapy. We employed pathology to evaluate the therapeutic efficacies and considered complete response (G4) & pathologic complete response (PCR) as efficacious. Fourfold table Chi-square test and binary Logistic regression were used to analyze the relationship between the above features and therapeutic efficacies. RESULTS: The overall efficacy rate of neoadjuvant chemotherapy was 58.1% (61/105) and the PCR rate 27.6% (29/105). The positive expression rates of PTEN, p-AKT and p-mTOR were 52.4% (57/105), 68.6% (72/105) and 43.8% (46/105) respectively. Fourfold table Chi-square test showed the difference between p-mTOR and therapeutic efficacy was significant statistically (P = 0.003) and also the difference between p-mTOR and PCR (P = 0.001). Binary Logistic regression showed the difference between p-mTOR and therapeutic efficiency was significant statistically, and also the difference between p-mTOR and PCR (both P < 0.01). The differential expressions of p-mTOR and p-AKT were statistically significant (P = 0.000) and so were those of p-AKT and PR (P = 0.035). CONCLUSIONS: The status of p-mTOR has predictive values for taxane-based neoadjuvant chemotherapy. The patients with a low level of p-mTOR are more responsive to thermotherapy while those with a high level of p-mTOR have a worse efficacy.

Survival Benefit of Surgical Treatment Added Into Systemic Treatment for Isolated Breast Cancer Liver Metastases: A Systematic Review and Meta-Analysis.

Background: Compared with systemic treatment alone, whether surgical treatment combined with systemic treatment can improve survival outcomes of patients with isolated breast cancer liver metastases (BCLM) is still controversial. This meta-analysis was designed to evaluate the efficacy of surgical treatment for patients with isolated BCLM. Methods: A systematic search of PubMed, Embase, and Cochrane Library up to May 13, 2021 was conducted for relevant studies. The primary outcome was overall survival. The meta-analysis was performed using R software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by funnel plots and Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity. Results: 9 retrospective studies involving 13 cohorts (7 unmatched cohorts and 6 matched cohorts) were included in this study. The surgical cohorts had better overall survival than the systemic cohorts in the pooled analysis of all the included studies, in the subgroup analysis of liver resection, and in the subset of the matched cohorts. Conclusions: Compared with systemic treatment alone, surgical treatment combined with systemic treatment was proven to be associated with superior survival outcomes, which should be considered in selected patients with isolated BCLM.

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.

Prognostic value of tumor-infiltrating lymphocyte subtypes in residual tumors of patients with triple-negative breast cancer after neoadjuvant chemotherapy.

BACKGROUND: After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC. METHODS: Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics. RESULTS: A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17-106 months). There was no significant correlation between the infiltrate density of CD4, CD8, CD20, and CD68 lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8-TILs (DFS: P = 0.018) and low CD20-TILs (OS: P = 0.042). Further analysis showed that patients with CD4/CD20 ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8/CD20 ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis. CONCLUSIONS: Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

[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.

[A prospective study of FOLFOX7 scheme as neoadjuvant chemotherapy for stage III gastric adenocarcinoma].

OBJECTIVE: To evaluate the efficacy and safety of FOLFOX7 scheme as neoadjuvant chemotherapy in patients with stage III gastric adenocarcinoma. METHODS: From May 2005 to May 2007, 27 patients with stage III gastric adenocarcinoma were given neoadjuvant chemotherapy with FOLFOX7 scheme. Gastroscopy, endoscopic ultrasonography, abdominal B ultrasonography and abdominal CT was taken before chemotherapy and after 2 - 4 cycles of neoadjuvant chemotherapy to evaluate the objective response rate of the tumor. Then operations were carried out and the pathological responses was evaluated in those cases. The safety, objective response rate and pathological rate of neoadjuvant chemotherapy was assessed according to NCI-CTC v3.0, RECIST 2000, and the criteria established by Japanese Research Society for Gastric Cancer, respectively. R0 resection rate and surgery-related complications was also assessed in this group. RESULTS: The treatment was well tolerated, no grade 3 - 5 toxicity was observed. Complete response was obtained in 1 case, and partial response in 18 patients, overall response rate was 70.4% (19/27). Twenty-six patients received operation and R0 resection rate was 88.4% (23/26); no patient died in the perioperative period. The pathological response rate of patients had R0 excision was 60.9% (14/23). CONCLUSION: FOLFOX7 scheme as neoadjuvant chemotherapy for selected patients with stage III gastric adenocarcinoma can be well tolerated, it could induce tumor down-staging and improve R0 resection rate, although the long term efficacy remains to be evaluated.

[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.