[The effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator flap breast reconstruction].

Objective: To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Methods: Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast surgery, Fudan University shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results: The controll groups showed higher aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ²=15.079,P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions: Correlation was observed between adiuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.

[Analysis on probability of premature death and cause eliminated life expectancy of major non-communicable diseases in Chongqing Municipality, 2016].

Objective: To analyze the premature death probability and cause-eliminated life expectancy of cardiovascular disease, cancer, chronic respiratory disease and diabetes in Chongqing residents in 2016 so as to provide recommendation for non-communicable diseases (NCDs) prevention and control in Chongqing. Methods: Death cases of Chongqing Municipality between January 1(st) and December 31(st), 2016 were reported through death case registry system of national center for disease prevention and control. Death cases were sorted by international classification of disease (ICD-10). Mortality rate, standardized mortality rate, constituent ratio, premature death probability, life expectancy, and cause-eliminated life expectancy of four major NCDs were analyzed. Results: A total of 218 004 death cases were reported in Chongqing, 2016, and the mortality rate was 731.73/100 000. Of them, a total of 179 637 death cases of the four major NCDs including cardiovascular disease, cancer, chronic respiratory disease and diabetes were reported, accounting for 82.40% of all death cases. The mortality rate and standardized mortality rate of four major NCDs was 602.95/100 000 and 455.82/100 000, respectively. The premature death probability of four major NCDs was 15.96%, and males (25.39%) had a higher premature death probability than females (10.78%). The premature death probability of cardiovascular disease, cancer, chronic respiratory disease, and diabetes were 6.01%, 8.32%, 2.05%, and 0.43%, respectively. Life expectancy would increase by 6.02, 3.19, 1.89, and 0.19 years, after eliminating cardiovascular disease, cancer, chronic respiratory disease and diabetes respectively. Conclusion: The premature death probability of major NCDs was high in Chongqing, and males had a higher premature death probability than females did. Intervention and health management of the population should be conducted according to different gender-based risk factors to reduce the premature death probability.

[Incidental internal mammary lymph node biopsy in 113 cases of breast cancer undergoingfree abdominal flap breast reconstruction and its influencing factors].

Objective: The aim of the current study is to determine the clinical value of incidental internal mammary lymph node biopsy in free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels and to investigate the risk factors of internal mammary lymph nodes metastasis. Methods: The clinical data of all patients who underwent free abdominal flap breast reconstruction using internal mammary vessels as recipient vessels from November 2006 to December 2015 in the Department of Breast Surgery, Fudan University Shanghai Cancer Center were reviewed in the study. The incidence of internal mammary lymph node biopsy and the rate of metastasis were analyzed. Statistical analysis was conducted to evaluate the risk factors of internal mammary lymph node metastasis. Results: A total of 113 patients met the inclusion criteria, 53 (46.9%) of whom had internal mammary lymph nodes harvested. Four of these were positive for metastatic disease, all in immediate breast reconstructions. The incidence of metastasis was 7.5% in patients who had successful internal mammary lymph node biopsies.The multi-variate Logistic regression analysis showed that invasive tumor size, tumor location and axillary lymph node metastasis were not risk factors for internal mammary lymph node metastasis (P>0.05). Conclusions: Internal mammary lymph nodes found incidentally during recipient vessel exposure may provide important information about internal mammary lymph node metastasis in free flap breast reconstruction. This approach for internal mammary lymph node biopsy reveals an appreciable success rate and is convenient in clinical practice. The size of invasive tumor and the axillary lymph node metastasis are probably associated with internal mammary lymph node positivity.

Assessment of surgical outcomes and oncological safety for submental artery perforator flap reconstruction after ablation of oral cancer.

The submental artery perforator flap (SAPF) has been a new option for the intraoral reconstruction of oral squamous cell carcinoma (OSCC) patients in recent years, but its surgical outcomes have not been well assessed. We compared the surgical outcomes and oncological safety of SAPF reconstruction for medium-sized soft-tissue defects after the ablation of primary oral cancer with traditional submental island flaps (SIF) and anterolateral thigh perforator flaps (ALTPF). Fifty-one SAPFs, 30 SIF, and 74 ALTPF were reviewed for the intraoral medium-sized reconstructions after the ablation of oral cancer from our institutional clinical oncological databases. We performed comparative assessments on the variables of surgical outcome and oncological safety among the 3 cohorts. A Kaplan-Meier estimate of survival for each flap was calculated. Operating time was significantly reduced in the SIF and SAPF groups than ALTPF (p = 0.021 and 0.014, respectively). Flap thickness of SAPF was the significantly thinnest (mean 0.5 cm) among three groups. The common complications of donor site for both SAPF and SIF group were incision dehiscence and orocutaneous fistula. There was no significant difference in disease-free survival (DFS) among the 3 groups. However, several OSCC patients with the SIF reconstruction were found to have recurrences with a metastatic lymph node under the flap after the first operation. SAPF could be a versatile choice of the intraoral reconstruction for the medium-sized soft-tissue defects after the ablation of oral cancer.

Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer.

BACKGROUND: To evaluate the activity and safety of nonanthracycline-containing weekly PCb [paclitaxel (Taxol) plus carboplatin] regimen in neoadjuvant treatment of breast cancer. PATIENTS AND METHODS: Eligible patients were assigned to receive four cycles of PCb with dose of paclitaxel 80 mg/m(2) and carboplatin at an area under the curve of 2 mg x min/ml, given day 1, day 8 and day 15 of every 4 weeks. Pathological complete remission (pCR) was defined as no invasive cancer in breast and axillary samples. RESULTS: Overall, 107 consecutive patients received weekly PCb treatment from December 2007 to December 2008, and one was diagnosed with bilateral breast cancer. A total of 85.2% of patients were initially diagnosed with stage III diseases. Clinical response rate was 86.1% with complete remission rate 32.4%. Twenty-one patients achieved pCR after neoadjuvant treatment, with pCR rate 19.4%. The incidence of grade 3-4 neutropenia was 40.2% and only one patient was reported with febrile neutropenia. Severe anemia and thrombocytopenia occurred in 4.7% and 0.9%, respectively, of patients. Peripheral neuropathy was frequent but never severe. Patients with estrogen receptor-negative, progesterone receptor-negative, triple-negative or human epidermal growth factor receptor 2 (Her2)-positive subtype disease had higher pCR. CONCLUSIONS: Weekly PCb regimen was very active and tolerable as neoadjuvant treatment of breast cancer. This weekly PCb regimen should consider as a reasonable nonanthracycline-containing option in the neoadjuvant treatment of breast cancer.

[Factors associated with sleep quality during first and second trimester in Chinese pregnant woman].

Objective: To investigate sleep quality in pregnant women during their first and second trimester and to identify risk factors. Methods: Data was from the Chinese Pregnant Women Cohort Study. A total of 3 618 pregnant women were included, with the exclusion 346 women who had missing information. Sociodemographic, health-related behavior, depression and sleep quality information were collected and analyzed. Logistic regression analysis were used to explore the influencing factors of sleep quality in pregnant women. Results: Among the 3 618 pregnant woman 28.2% had poor sleep quality in their first trimester and 28.7% in the second trimester. 15.2% pregnant women had progressively worse sleep and 13.0% had persistently poor sleep had pregnant women were generally suffered from poor sleep quality, difficulty falling asleep, sleep disorders and daily fatigue. Regular diet (OR=0.75, 95%CI: 0.62-0.92) and work (OR=0.84,95%CI: 0.71-0.99) in the first trimester were protective factors of sleep quality in pregnant women. Age ≥30 year old (OR=1.19, 95%CI: 1.03-1.37), passive smoking (OR=1.18, 95%CI: 1.02-1.36) and depression (OR=2.25, 95%CI: 1.95-2.61) in the first trimester were risk factors. Conclusions: The rate of poor sleep quality are high among Chinese pregnant woman during their first and second trimester. The risk factors of sleep quality are multiple. Regular diet and work, reduction of tobacco exposure, alleviation of depression symptom may help improve sleep quality among pregnant women.

[Risk factors for preterm birth, low birth weight and small for gestational age: a prospective cohort study].

Objective: To study the relationship between exposure factors in early pregnancy and preterm birth (PB), low birth weight (LBW) and small for gestational age (SGA) of neonates. Methods: A total of 3 172 pregnant women who were enrolled in the project of Chinese Pregnant Women Cohort Study-Peking Union Medical College (CPWCS-PUMC) from July 25, 2017 to July 24, 2018 and delivered before December 31, 2018 were selected as subjects in this study. The relationship between exposure factors in early pregnancy and adverse outcomes of neonatal delivery was analyzed by using binary logistic regression analysis. Results: The incidence rates of PB, LBW and SGA were 4.76%, 3.53% and 5.74%, respectively. In terms of PB, the analysis results showed that the gestational weight gain (GWG) and living in northern China were protective factors, while premature rupture of membranes, gestational hypertension, dental examination or treatment within 1-3 years and family with 3-4 members were risk factors. In the respect of LBW, GWG and daily consumption of milk and dairy products were the protective factors, while premature rupture of membranes, gestational hypertension, sedentary working time more than 6 hours, dental examination or treatment within 1-3 years and passive smoking were risk factors. For SGA, baby girl, passive smoking, peanut oil consumption and unsalted taste were risk factors, while folic acid supplementation was protective factor. Conclusion: The risk factors for PB, LBW and SGA were multifactorial, and relevant specific measures should be taken to reduce the occurrence of adverse neonatal outcomes.

[Current status on prevalence, treatment and management of hypertension among Chinese adults in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To investigate the current status of prevalence, treatment, and management on hypertension among Chinese adults from the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: We selected a total of 4 000 residents aged ≥18 years for this questionnaire-based survey by multi-stage clustering sampling in 10 National Demonstration Areas between November and December, 2016. Results: There were 3 891 effective questionnaires. The self-reported prevalence of hypertension among aged ≥35 years was 31.47% (1 011/3 213). For the past two weeks, the self-reported treatment of hypertension was 86.75%(877/1 011), with the rates of guidance as 56.87% (575/1 011) on physical activity, 40.95% (414/1 011) on diet, 38.33% (385/1 011) on weight management, and 22.75% (228/1 011) on smoking cessation. For the past 12 months, 74.68% (755/1 011) of the residents aged ≥35 years were under the proper management and 62.12% (628/1 011) of them were under the standardized management programs. The follow-up program lasted for 4 (P(25)-P(75): 4-12) times per year, with 15 (P(25)-P(75): 10-20) minutes per each visit. Hypertensive patients would mainly visit the outpatient clinics (53.51%), followed by home visits (22.91%) and telephone calls (13.64%). Rate of satisfaction on management services was 94.83% (716/755) from the hypertensive patients. Multivariate analysis showed that the rate of self-reported treatment (OR=1.986, 95%CI: 1.222-3.228) and self-reported standardized management (OR=2.204, 95%CI: 1.519-3.199) on hypertension were higher in the Demonstration Areas with higher implementation scores of self-reported non-communicable diseases management. Conclusions: Prevention and management on hypertension in the Demonstration Areas had met the requirement set for the Demonstration Areas during the "12th Five-Year Plan" . Projects on setting up the National Non-communicable Diseases Demonstration Areas had played an active role in promoting the standardized management program on hypertension.

[Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention (OR=6.591, 95%CI: 5.188-8.373), salt reduction (OR=1.352, 95%CI: 1.151-1.589), oil reduction (OR=1.477, 95%CI: 1.249-1.746) and recommendation on physical activities (OR=1.975, 95%CI: 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local platform for the control and prevention of non-communicable diseases, and thus become an important 'carrier' for chronic disease prevention and control programs in China.

Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential.

In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.

[Application of autoregressive integrated moving average model in predicting the reported notifiable communicable diseases in China].

Objective: To develop the models for predicting the reported legally notifiable diseases in China. Autoregressive integrated moving average (ARIMA) model was applied to forecast the trend of diseases. Methods: Cases used for building the model were from of the records of Notifiable Infectious Diseases in China from May 2009 to July 2016 with R software and the model's predictive ability was tested by the data from August 2016 to January 2017. Results: A strong seasonal nature was seen in the reported cases of notifiable communicable diseases, with the lowest point in February and highest peak in June. ARIMA (4, 1, 0) (1, 1, 1)(12) model was established by the team to forecast the notifiable communicable diseases. Data showed that the biggest and lowest relative errors appeared as 9.78% and 2.21%, respectively, with the mean of the relative error as 5.39%. Conclusion: Based on the results of this study, the ARIMA (4, 1, 0) (1, 1, 1)(12) model seemed to have had the sound prediction of notifiable communicable diseases in China.

Genistein exerts multiple suppressive effects on human breast carcinoma cells.

Dietary genistein, a natural flavone compound found in soy, has been proposed to be responsible for the low rate of breast cancer in Asian women. The cellular mechanisms of genistein's chemopreventive effects in vio have been largely unexplored. In our previous studies, we found that genistein exerted pronounced antiproliferative effects on both estrogen receptor-positive and -negative human breast carcinoma cells through G2-M arrest, induction of p21WAF1/CIP1 expression, and apoptosis. Because chemopreventive effects need not be limited to antiproliferation, we decided to examine whether genistein exerted other suppressive effects on breast carcinoma progression. Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1. These in vitro and in vivo studies demonstrate that genistein exerts multiple suppressive effects on breast carcinoma cells, suggesting that its mechanism of chemoprevention is pleiotropic.

Better predictive value of axillary lymph node (ALN) status after systemic therapy for operable HER2-overexpressing breast cancer: A single-institution retrospective study.

BACKGROUND: Thresholds for using Preoperative Systemic Therapy (PreST) have decreased to include early breast cancer. This study investigates the predictive value of axillary lymph node (ALN) status before and after systemic therapy and discusses whether it is better to receive PreST first in operable HER2-overexpressing breast cancer patients. METHODS: From January 2008 to June 2013 at Fudan University Shanghai Cancer Center, we identified 406 eligible female patients with stage II-IIIa, operable and pathologically confirmed HER2-overexpressing invasive ductal carcinoma. Of these patients, 269 underwent surgery first followed by chemotherapy plus trastuzumab (chemo-trastuzumab) (SurgFirst group), whereas 137 received systemic chemo-trastuzumab therapy first followed by surgery (STFirst group). Disease-free survival (DFS) and overall survival (OS) were evaluated according to different ALN statuses using the Kaplan-Meier method. Multivariate COX model analyses were also conducted. RESULTS: The median follow-up time was 47 months (IQR: 37-60). Both ALN status and overall pathological complete remission (pCR) status were shown to be significant for the prediction of DFS (p = 0.001 and p = 0.005, respectively) and OS (p = 0.009 and p = 0.027, respectively) in the STFirst group. However, patients with positive ALN(s) did not experience significantly poorer survival compared with those with negative ALN in the SurgFirst group. The adjusted hazard ratios (HRs) for positive ALN status in the STFirst and SurgFirst groups were 6.66 (p = 0.001, 95%CI: 2.18-20.38) and 2.40 (p = 0.126, 95%CI: 0.78-7.34), respectively. CONCLUSION: The ALN status after systemic chemo-trastuzumab therapy better predicts the survival outcome. We recommend the application of PreST followed by surgery in patients with operable HER2-overexpressing breast cancer.

p53 mutation in plasma DNA and its prognostic value in breast cancer patients.

PURPOSE: Tumor-specific DNA has recently been detected in the plasma of lung, head and neck, breast, and colon cancer patients. Detection of tumor-specific genetic materials in cancer patients at sites distant from the tumor, such as in the blood, may provide a unique and valuable tumor marker for diagnosis and prognosis. EXPERIMENTAL DESIGN: The present investigation was aimed at determining the presence of p53 mutations in the peripheral blood of breast cancer patients and its prognostic value in these patients. RESULTS: In this study, we found that the mean concentration of plasma DNA in healthy women was 21 ng/ml, whereas in patients with breast cancer the mean concentration was 211 ng/ml (P < 0.01). p53 mutations were detected in the primary tumors of 46 of 126 (36.5%) breast cancer patients. Of these 46 patients, 30 (65.1%) were found to have p53 mutations in their plasma DNA. p53 mutations in plasma DNA were strongly correlated with clinical stage, tumor size, lymph node (LN) metastasis, and estrogen receptor status (P < 0.05). After a median follow-up of 29 months, univariate and multivariate analysis revealed that both primary tumor and plasma DNA p53 mutations were significant prognostic factors for both relapse-free and overall survival. Furthermore, we demonstrated that patients with both primary tumor and plasma p53 mutations have the worst survival. This outcome occurs in both LN-positive and LN-negative groups. Thirteen of the 22 (59%) patients with recurrence and/or metastasis later had detectable p53 mutations in their plasma DNA. CONCLUSIONS: Detection of p53 mutations in plasma DNA may be used as a prognostic factor and an early marker to indicate recurrence or distant metastasis.

Over expression of aromatase protein is highly related to MMPs levels in human breast carcinomas.

Estrogens can play a critical role in the development of breast cancer. Aromatase which catalyzes the formation of aromatic C18 estrogens from C19 androgens is regarded to be responsible for the cancer local production of estrogen. Studies not only from aromatase transfected breast cancer cells, but also transgenic mouse, which overexpressed aromatase, demonstrated that in situ produced estrogen plays more important roles than circulating estrogens in breast tumor promotion and progression. Matrix-metalloproteinases (MMPs) have been implicated in the proeolytic process, which play important roles in the aggressiveness of cancer cells including invasion of adjacent tissue and metastasis to distant sites. Expression of MMP2 and 9 may be stimulated by estrogens in hormonal dependent breast cancers, since tumor aromatase can stimulate breast cancer growth and progression in both an autocrine and a paracrine manner. Theoretically aromatase overexpression, that causes relatively high estrogen concentration in situ, may be positively related to MMP2 and 9 expression, indicate worse prognosis in breast cancers, and maybe insensitive to tamoxifen therapy. In the present study, we studied the expression of aromatase activity and MMPs in human breast carcinoma both in vitro and in vivo. In human breast carcinoma cell lines including MCF-7, MDA-MB-231 and MDA-MB-435, the expression of aromatase levels both in mRNA and protein activity was related to MMP2 and MMP9. In humam breast cancer samples, we demonstrated that aromatase expressions were strongly associated with MMP2 and MMP9 levels. It was interesting to observe that the positive relationship was only present in the ER and/or PR positive patients. This may indicate that both MMP2 and MMP9 were up regulated by estrogen produced by aromatase through ER. So in endocrine therapy, either blocking the ER by tamoxifen or inhibiting the aromatase by aromatase inhibitors for example letrozole, may both inhibit tumor growth and lower the metastatic potential especially in ER positive breast cancer patients by means of down-regulation of MMP2/9.

Nodal ratio of positive to excised nodes, but not number of positive lymph nodes is better to predict group to avoid chemotherapy among postmenopausal ER-positive, lymph node-positive T1-T2 breast cancer patients.

AIM OF STUDY: To identify whether nodal ratio (NR) of positive to excised nodes is superior to number of positive lymph nodes to predict group to avoid chemotherapy among postmenopausal ER-positive, lymph node-positive, T1-T2 breast cancer patients. MATERIALS AND METHODS: Postmenopausal estrogen receptor (ER)-positive, lymph node-positive patients who received endocrine therapy (n = 173) with complete baseline data in our hospital between 2000 and 2006 were included. The disease-free survival (DFS) was compared. Survival analysis was performed using Kaplan-Meier method. Cox proportional hazard models were used to evaluate the prognostic value of chemotherapy with different NR for DFS. P--values less than 0.05 were regarded as significant. RESULTS: The median follow-up was 72 months. Three of 13 variables analyzed remained significantly prognostic for survival in the Cox proportional hazards model. These included age (hazard ratio (HR) =1.642, 95% confidence interval (CI) =1.154-2.337, P = 0.006); histological grade (HR = 2.463,95% CI = 1.389-4.367, P = 0.002); and NR (HR = 2.280, 95% CI = 1.113-4.671, P = 0.024). Subgroup analysis by NR status showed that in patients with NR ≥ 0.20, chemotherapy significantly improves DFS (HR = 0.360, 95% CI = 0.195-0.663, P = 0.001); while in patients with NR < 0.20, chemotherapy did not significantly affect DFS (HR = 0.677, 95% CI = 0.227-2.107, P = 0.493). Radiotherapy is an important factor that improves DFS in lymph node-positive patients, so it is considered in all analysis. CONCLUSION: This retrospective analysis demonstrates that NR of positive to excised nodes, but not number of positive lymph nodes is better to predict group to avoid chemotherapy among postmenopausal ER-positive, lymph node-positive T1-T2 breast cancer patients.

Antigenic profiles of disseminated breast tumour cells and microenvironment in bone marrow.

AIMS: Thirty per cent of breast cancer patients with axillary lymph node negative at primary surgery will relapse within 10 years. This may be caused by disseminated tumour cells from the primary tumour. This study report the phenotypic profiles of disseminated tumour cells and microenvironmental characteristics in bone marrow of breast cancer. METHODS: We detected the biologic markers on the disseminated tumour cells with immunocytochemical staining, analysed the immunological changes through flow-cytometry, and investigated the u- PA activity in the plasma of bone marrow. RESULTS: With the immunocytochemical staining of EMA and CK19, we detected micrometastasis in thirty out of 72 (41.67%) breast cancer patients. Compared with the primary tumours, disseminated tumour cells expressed low protein cyclin D1, P53, Ki-67, EGFR, and high protein P21. The percentage of memory CD4+ T cells was significantly higher in the micrometastasis-positive group than in the micrometastasis-negative group. Tumour size and axillary lymph node status were found to be significantly correlated with the u- PA activity level. CONCLUSIONS: Immunophenotypic profiles of disseminated tumour cells could be measured by immunocytochemical staining and microenvironment can be analysed by flow cytometry.

Genistein inhibits both constitutive and EGF-stimulated invasion in ER-negative human breast carcinoma cell lines.

Genistein, a natural flavone compound, has been proposed to be responsible for the lower rate of breast cancer in Asian women. The cellular mechanisms of genistein's inhibition of breast cancer progression are largely unknown. In a previous study our laboratory has presented evidence that genistein inhibits cell proliferation of breast carcinoma cells, an inhibition which is associated with a specific G2/M arrest, induction of p21WAF/CIP1 expression and apoptosis. In the present study, we present experimental evidence that illustrates that the actions of genistein are not limited to anti-proliferation: we show that genistein can inhibit both constitutive as well as epidermal growth factor (EGF)-stimulated invasion in estrogen receptor (ER)-negative human breast carcinoma lines, MDA-MB-231 and MDA-MB-468. This inhibition is characterized by the down regulation of MMP-9 (92 kDa type IV collagenase) and up regulation of TIMP-1 (tissue inhibitor of metalloproteinases) and the trypsin inhibitors: protease nexin-II (PN-II) and alpha 1-antitrypsin (alpha 1-AT). The in vivo actions of genistein may therefore extend beyond those traditionally implicated in chemoprevention, e.g., antiproliferation; genistein may act in vivo by blocking additional stages of breast cancer progression such as those stages resulting in invasion and metastasis.

Genistein's "ER-dependent and independent" actions are mediated through ER pathways in ER-positive breast carcinoma cell lines.

Genistein, a natural flavone found in soy has been postulated to be responsible for lowering the rate of breast cancer in Asian women. Our previous studies have shown that genistein exerts multiple suppressive effects on both estrogen receptor positive (ER+) as well as estrogen receptor negative (ER-) human breast carcinoma lines suggesting that the mechanisms of these effects may be independent of ER pathways. In the present study however we provide evidence that in the ER+ MCF-7, T47D and 549 lines but not in the ER-MDA-MB-231 and MDA-MB-468 lines both presumed "ER-dependent" and "ER-independent" actions of genistein are mediated through ER pathways. Genistein's antiproliferative effects are estrogen dependent in these ER+ lines, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Genistein also inhibits the expression of ER-downstream genes including pS2 and TGF-beta in these ER+ lines and this inhibition is also dependent on the presence of estrogen. Genistein inhibits estrogen-induced protein tyrosine kinase (PTK) activity. Genistein is only a weak transcriptional activator and actually decreases ERE-CAT levels induced by 17-beta estradiol in the ER+ lines. Genistein also decreases steady state ER mRNA only in the presence of estrogen in the ER+ lines thereby manifesting another suppression of and through the ER pathway. Our observations resurrect the hypothesis that genistein functions as a "good estrogen" in ER+ breast carcinomas. Since chemopreventive effects of genistein would be targeted to normal ER-positive ductal-lobular cells of the breast, this "good estrogen" action of genistein is most relevant to our understanding of chemoprevention.

Fiberoptic ductoscopy for breast cancer patients with nipple discharge.

BACKGROUND: Breast cancer and precancer are thought to originate in the lining of the milk duct, but until recently, we have not had direct access to this area other than in tissue removed blindly by core biopsy or fine-needle aspiration. Fiberoptic ductoscopy (FDS) is an emerging technique that allows direct visual access of the ductal system of the breast through nipple orifice cannulation and exploration. To date, this technique has been used only in pilot studies. Previously, we have demonstrated that fiberoptic ductoscopy in patients with and without nipple discharge is a safe and effective means of visualizing the intraductal lesion. When combined with cytology, it is a screening technique that has high predictive value. METHODS: We applied ductoscopy to 415 women with nipple discharge with the specific intent of detecting those patients with nipple discharge who had intraductal carcinoma (DCIS) as the basis of their discharge. RESULTS: In this cohort of patients, ductoscopy was successful in visualizing an intraductal lesion in 166 patients (40%). In these cases, ductal lavage following ductoscopy increased the yield of cytologically interpretable ductal epithelial cells 100-fold compared to discharge fluid alone. In the majority of these patients, FDS examination detected lesions that had the appearance of typical papillomas. However, in 10 patients, the intraductal lesion exhibited one of several atypical features, including bleeding, circumferential obstruction, and gross fungating projections. In eight of these patients, the subsequent histopathology turned out to be DCIS. In two of these eight patients, endoscopic biopsy revealed cytologically malignant cells; in two others, ductal lavage (washings) revealed cytologically malignant cells. In three additional patients, although FDS examination uncovered a typical papilloma that was not biopsied, ductal lavage (washings) revealed cytologically malignant cells. On surgical pathology review of the extirpated lesions, all 11 patients were subsequently shown to have DCIS. Of these 11 cases of DCIS that were initially detected with a combination of FDS and ductal lavage cytology, six were completely negative on mammogram and physical exam. CONCLUSION: Although nipple discharge is an unusual presentation for DCIS, in patients with nipple discharge, FDS with ductal lavage cytology is a useful technique for diagnosing DCIS prior to definitive surgery.