XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

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 Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

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.

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 case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

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.

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

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.

[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.

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.

[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.

[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.

[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.

Correlation between dynamic contrast-enhanced MRI and histopathology in the measurement of tumor and breast volume and their ratio in breast cancer patients: a prospective study.

BACKGROUND: Earlier studies have examined the association between the diameter of primary tumors measured by magnetic resonance imaging (MRI) and histopathology in breast cancer patients. However, the diameter does not completely describe the dimensions of the breast tumor or its volumetric proportion relative to the whole breast. The association between breast tumor volume/breast volume ratios measured by these two techniques has not been reported. METHODS: Seventy-three patients were recruited from female patients with primary breast tumors admitted to our center between January and December 2010. They were divided into two groups. Group A (n = 46) underwent modified radical mastectomy (MRM), and Group B (n = 27) underwent preoperative neoadjuvant chemotherapy before MRM. They were examined by dynamic-contrast enhanced MRI (DCE-MRI) to measure breast volumes (BVs), tumor volumes (TVs), and tumor volume/breast volume ratios (TV/BV). These measurements were compared with histopathology results after MRM, and the associations between MRI and pathology were analyzed by linear regression and Bland-Altman analysis. RESULTS: For Group A, the correlation coefficients for BVs, TVs, and TV/BV ratios measured by the two techniques were 0.938, 0.921, and 0.897 (all P < 0.001), respectively. For Group B, the correlation coefficients for BVs, TVs, and TV/BV ratios were 0.936, 0.902, and 0.869 (all P < 0.01), respectively. The results suggest statistically significant correlations between these parameters measured by the two techniques for both groups. CONCLUSION: For these patients, BVs, TVs, and TV/BV ratios measured by DCE-MRI significantly correlated with those determined by histopathology.

A case-control study on risk factors of breast cancer in China.

INTRODUCTION: To screen the risk factors associated with breast cancer among Chinese women in order to evaluate the individual risk of developing breast cancer among women in China. MATERIAL AND METHODS: A case-control study on 416 breast cancer patients and 1156 matched controls was conducted in 14 hospitals in 8 provinces of China in 2008. Controls were age- and region-matched to the cases. Clinicians conducted in-person interviews with the subjects to collect information on demographics and suspected risk factors for breast cancer that are known worldwide. Conditional logistic regression was used to derive odds ratios (OR) and 95% confidence intervals (CI) for the associations between risk factors and breast cancer. RESULTS: Compared with matched controls, women with breast cancer were significantly more likely to have higher body mass index (BMI, OR = 4.07, 95% CI: 2.98-5.55), history of benign breast disease (BBD) biopsy (OR = 1.68, 95% CI: 1.19-2.38), older age of menarche (AOM) (OR = 1.41, 95% CI: 1.07-1.87), stress anticipation (SA), for grade 1-4, OR = 2.15, 95% CI: 1.26-3.66; for grade 5-9, OR = 3.48, 95% CI: 2.03-5.95) and menopause (OR = 2.22, 95% CI: 1.50-3.282) at the level of p < 0.05. Family history of breast cancer (FHBC) in first-degree relatives (OR = 1.66, 95% CI: 0.77-3.59) and use of oral contraceptives (OC) (OR = 1.59, 95% CI: 0.83-3.05) were associated with an increased risk of breast cancer at the level of p < 0.20. CONCLUSIONS: Our results showed that BMI, history of BBD biopsy, older AOM, SA and menopause were associated with increased risk of breast cancer among Chinese women. The findings derived from the study provided some suggestions for population-based prevention and control of breast cancer in China.

Role of granulocyte colony-stimulating factor in paclitaxel-induced intestinal barrier breakdown and bacterial translocation in rats.

BACKGROUND: Chemotherapy causes breakdown of the intestinal barrier, which may lead to bacterial translocation. Paclitaxel, an anti-tubulin agent, has many side effects; however, its effect on the intestinal barrier is unknown. Previous studies show that granulocyte colony-stimulating factor (G-CSF) plays an important role in modulating intestinal barrier function, but these studies are not conclusive. Here, we investigated the effects of paclitaxel on the intestinal barrier, and whether G-CSF could prevent paclitaxel-induced bacterial translocation. METHODS: Twenty-four male Sprague-Dawley rats were divided into three groups: control group, paclitaxel group and paclitaxel + G-CSF group. Intestinal permeability was measured by the urinary excretion rates of lactulose and mannitol administered by gavage. The mesenteric lymph nodes, spleen and liver were aseptically harvested for bacterial culture.Endotoxin levels and white blood cell (WBC) counts were measured and bacterial quantification performed using relative real-time PCR. Jejunum samples were also obtained for histological observation. Intestinal apoptosis was evaluated using a fragmented DNA assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate(dUTP)-biotin nick end-labeling staining. One-way analysis of variance and Fisher's exact test were used to compare differences between groups. RESULTS: Paclitaxel induced apoptosis in 12.5% of jejunum villus cells, which was reduced to 3.8% by G-CSF treatment.Apoptosis in the control group was 0.6%. Paclitaxel treatment also resulted in villus atrophy, increased intestinal permeability and a reduction in the WBC count. G-CSF treatment resulted in increased villus height and returned WBC counts to normal levels. No bacterial translocation was detected in the control group, whereas 6/8, 8/8, and 8/8 rats in the paclitaxel group were culture-positive in the liver, spleen and mesenteric lymph nodes, respectively. Bacterial translocation was partially inhibited by G-CSF. CONCLUSIONS: Paclitaxel disrupts the intestinal barrier, resulting in bacterial translocation. G-CSF treatment protects the intestinal barrier, prevents bacterial translocation, and attenuates paclitaxel-induced intestinal side-effects.