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1.  A Nation-Wide Multicenter 10-Year (1999-2008) Retrospective Clinical Study of Endocrine Therapy for Chinese Females with Breast Cancer 
PLoS ONE  2014;9(7):e100159.
Endocrine therapy (ET) is one of the main systemic treatments for patients with breast cancer. To our knowledge, few studies have addressed the performance of ET or relevant influencing factors in cancer treatment in China. By retrospectively analyzing the clinicopathological data on breast cancer collected from representative hospitals of 7 traditional areas in China in one random month from each year between year 1999 and 2008, we found that: 1) The rate of the use of hormone receptor (HR) testing was 83.8% (3529/4211), with the estrogen receptor-positive (ER+) rate and/or the progesterone receptor-positive (PR+) rate being 67.9% (2395/3529), and the ER-PR rate being 32.1% (1134/3529). 2) Of the 1599 patients who had received ET, 999 patients (58.3%) were premenopausal while 600 (41.7%) were postmenopausal; 1598 patients received adjuvant hormonal therapy (AHT), whereas only 1 patient received palliative therapy. The medications mainly administered to patients were anti-estrogen agents (80.3% [1283/1598]), followed by AIs (15.5% [248/1598]). Of the 1598 patients receiving AHT, 1416 patients (88.6%) were positive for ER and/or PR, while 75 (4.7%) were negative for both and 108 patients (6.7%) had unknown HR status. The ratio of the use of endocrine therapy for breast cancer patients with ER+ and/or PR+ status was 60.0% (1416/2395). 3) Results from the logistic regression analysis revealed that geography, occupations, and history of chemotherapy and surgery were dependent factors affecting the application of ET in breast cancer treatment in China (P<0.001). In conclusion, the use of ET on Chinese women with breast cancer is increasingly and gradually accounted into the standardized process. Economic status, occupations, and history of chemotherapy and surgery were key factors affecting the application of ET. People residing in developed areas, engaging in mental labour, having history of chemotherapy and surgery are susceptible to accept ET.
PMCID: PMC4103779  PMID: 25036532
2.  Application of intraoperative frozen section examination in the management of female breast cancer in China: a nationwide, multicenter 10-year epidemiological study 
Intraoperative frozen section examination (IFSE) during breast cancer surgery can partly reflect the status of surgical treatment since the surgical method used directly determines the purpose of IFSE use in disease management. This study aims to investigate the application of, changing trends in, and factors influencing IFSE in the management of female breast cancer in China.
We collected the sociodemographic and clinical data of 4,211 breast cancer patients between 1999 and 2008 and statistically analyzed these data using χ2 or Fisher’s exact tests.
A total of 2,283 (54.22%) patients with breast cancer underwent IFSE. During the 10-year study period, IFSE use was associated with an increase in the number of sentinel lymph node biopsies (SLNB) and breast-conserving surgeries (BS) performed, with significant regional differences noted in this trend (P <0.05). Patients’ education, occupation, age, tumor size estimated by preoperative palpation, and the use of imaging examinations affected the purpose of IFSE use (P <0.05).
Our results show that the purpose of IFSE in the surgical treatment of breast cancer in China is gradually approaching that in developed countries. We believe that policymakers must address the differences in breast cancer treatment based on the socioeconomic status of patients. Lastly, the use of IFSE for determining tumor characteristics should be avoided as far as possible, and patient education and breast cancer screening programs tailored to the Chinese population should be established. Our findings may guide the formulation of breast cancer control strategies in China and other low-income countries.
PMCID: PMC4105393  PMID: 25034137
Application mode; Female breast cancer; Intraoperative frozen section examination; Sociodemographic factor
3.  Body Mass Index and Breast Cancer Defined by Biological Receptor Status in Pre-Menopausal and Post-Menopausal Women: A Multicenter Study in China 
PLoS ONE  2014;9(1):e87224.
Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women.
Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women.
Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (rs BMI, PR+ = 0.867, P = 0.001; rs BMI, HER2+ = 0.636, P = 0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m2 as the reference group were performed and found that BMI≥24 kg/m2 was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR = 1.420, 95% CI: 1.116–1.808, Wald = 8.116, P = 0.004).
Post-menopausal women with high BMI (≥24 kg/m2) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies.
PMCID: PMC3906138  PMID: 24489874
4.  Raman enhancement by graphene-Ga2O3 2D bilayer film 
2D β-Ga2O3 flakes on a continuous 2D graphene film were prepared by a one-step chemical vapor deposition on liquid gallium surface. The composite was characterized by optical microscopy, scanning electron microscopy, Raman spectroscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy (XPS). The experimental results indicate that Ga2O3 flakes grew on the surface of graphene film during the cooling process. In particular, tenfold enhancement of graphene Raman scattering signal was detected on Ga2O3 flakes, and XPS indicates the C-O bonding between graphene and Ga2O3. The mechanism of Raman enhancement was discussed. The 2D Ga2O3-2D graphene structure may possess potential applications.
PMCID: PMC3906882  PMID: 24472433
Graphene; Raman enhancement; Gallium oxide; Chemical vapor deposition
5.  Risk Factors for Breast Cancer Among Chinese Women: A 10-Year Nationwide Multicenter Cross-Sectional Study 
Journal of Epidemiology  2014;24(1):67-76.
The characteristics of established risk factors for breast cancer may vary among countries. A better understanding of local characteristics of risk factors may help in devising effective prevention strategies for breast cancer.
Information on exposures to risk factors was collected from the medical charts of 4211 women with breast cancer diagnosed during 1999–2008. The distributions of these exposures among regions, and by menopausal status and birth period, were compared with the χ2 test. Crude associations between the selected factors and breast cancer were estimated using the cases in the present study and a representative control population, which was selected from qualified published studies.
As compared with cases from less developed regions, those from more developed regions were significantly more likely to be nulliparous, had fewer childbirths (P < 0.05), and were less likely to have breastfed (P = 0.08). As compared with premenopausal cases, postmenopausal cases were more likely to be overweight and to have breastfed and had more childbirths (P < 0.05). The number of live births and rate of breastfeeding decreased in relation to birth period (P for trends <0.001). Overweight, late menopause, and family history of breast cancer were significantly associated with breast cancer among Chinese women.
Breast cancer incidence was associated with nulliparity and history of breastfeeding. Population attributable risks should be assessed, especially for more developed areas and young women. The effects of body mass index, age at menopause, and family history of breast cancer should be given priority during assessment of breast cancer risk among Chinese women.
PMCID: PMC3872527  PMID: 24270059
breast cancer; risk factors; nationwide; multicenter
6.  Signet-ring cell carcinoma of the breast: a case report 
Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under ‘mucin-producing carcinomas’ and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.
PMCID: PMC3751374  PMID: 23938020
Signet-ring cell carcinoma breast cancer
7.  Characterizing the Clustered Microcalcifications on Mammograms to Predict the Pathological Classification and Grading: A Mathematical Modeling Approach 
Journal of Digital Imaging  2011;24(5):764-771.
In this study, we explore a mathematical model to characterize the clustered microcalcifications on mammograms for predicting the pathological classification and grading. Our database consists of both retrospective cases (78 cases) and prospective cases (31 cases) with pathologically diagnosed clusters of microcalcifications on mammograms. The microcalcifications were divided into four grades: grade 0, benign breast disease including mastopathies (n = 12) and fibroadenomas (n = 20); grade 1, well-differentiated infiltrating ductal carcinoma (n = 12); grade 2, moderately differentiated infiltrating ductal carcinoma (n = 38); grade 3, poorly differentiated infiltrating ductal carcinoma (n = 27). A feature parameter, defined as the pattern form factor of microcalcification cluster θ by us, combines five computer-extracted image parameters of microcalcification clusters of those mammograms. In every case, only one imaging was selected for modeling analysis. A total of 109 imagings were adopted in current study. We find the existence of a positive relationship between the feature parameter θ and pathological grading G of microcalcifications in retrospective cases, which was expressed as G =  6.438 + 1.186 ×  Ln <θ>. The model above has been verified further by the prospective study with a comparative evaluation accuracy of approximately 77.42%. The binary predication simply for both benignancy and malignancy was also included using same but reshuffled data, and the receiver operating characteristic (ROC) analysis was performed with ROC value 0.74351∼0.79891. As one candidate for feature parameter in computer-aided diagnosis, the pattern form factor θ of clustered microcalcifications may be useful to predict the pathological grading and classification of microcalcification clusters on mammography in breast cancer.
PMCID: PMC3180539  PMID: 21512853
Algorithms; computer-aided diagnosis (CAD); mammography CAD; breast diseases; clustered microcalcification detection
8.  A case report of primary small cell carcinoma of the breast and review of the literature 
Chinese Journal of Cancer  2012;31(7):354-358.
Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.
PMCID: PMC3777496  PMID: 22516480
Small cell carcinoma; breast; neuroendocrine
9.  Joint Effects of Febrile Acute Infection and an Interferon-γ Polymorphism on Breast Cancer Risk 
PLoS ONE  2012;7(5):e37275.
There is an inverse relationship between febrile infection and the risk of malignancies. Interferon gamma (IFN-γ) plays an important role in fever induction and its expression increases with incubation at fever-range temperatures. Therefore, the genetic polymorphism of IFN-γ may modify the association of febrile infection with breast cancer risk.
Methodology and Principal Findings
Information on potential breast cancer risk factors, history of fever during the last 10 years, and blood specimens were collected from 839 incident breast cancer cases and 863 age-matched controls between October 2008 and June 2010 in Guangzhou, China. IFN-γ (rs2069705) was genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. We found that women who had experienced ≥1 fever per year had a decreased risk of breast cancer [ORs and 95% CI: 0.77 (0.61–0.99)] compared to those with less than one fever a year. This association only occurred in women with CT/TT genotypes [0.54 (0.37–0.77)] but not in those with the CC genotype [1.09 (0.77–1.55)]. The association of IFN-γ rs2069705 with the risk of breast cancer was not significant among all participants, while the CT/TT genotypes were significantly related to an elevated risk of breast cancer [1.32 (1.03–1.70)] among the women with <1 fever per year and to a reduced risk of breast cancer [0.63 (0.40–0.99)] among women with ≥1 fever per year compared to the CC genotype. A marked interaction between fever frequencies and the IFN-γ genotypes was observed (P for multiplicative and additive interactions were 0.005 and 0.058, respectively).
Our findings indicate a possible link between febrile acute infection and a decreased risk of breast cancer, and this association was modified by IFN-γ rs2069705.
PMCID: PMC3356273  PMID: 22624006
10.  Breast cancer stage at diagnosis and area-based socioeconomic status: a multicenter 10-year retrospective clinical epidemiological study in China 
BMC Cancer  2012;12:122.
Although socioeconomic status (SES) has been focused on as a key determinant of cancer stage at diagosis in western countries, there has been no systemic study on the relationship of SES and breast cancer stage at diagnosis in China.
The medical charts of 4,211 eligible breast cancer patients from 7 areas across China who were diagnosed between 1999 and 2008 were reviewed. Four area-based socioeconomic indicators were used to calculate area-based SES by cluster analysis. The associations between area-based SES and stage at diagnosis were analyzed by trend chi-square tests. Binary logistic regression was performed to estimate odds ratios for individual demographic characteristics' effects on cancer stages, stratified by area-based SES.
The individual demographic and pathologic characteristics of breast cancer cases were significantly different among the seven areas studied. More breast cancer cases in low SES areas (25.5%) were diagnosed later (stages III & IV) than those in high (20.4%) or highest (14.8%) SES areas (χ2 for trend = 80.79, P < 0.001). When area-based SES is controlled for, in high SES areas, cases with less education were more likely to be diagnosed at later stages compared with more educated cases. In low SES areas, working women appeared to be diagnosed at earlier breast cancer stages than were homemakers (OR: 0.18-0.26).
In China, women in low SES areas are more likely to be diagnosed at later breast cancer stages than those in high SES areas.
PMCID: PMC3338083  PMID: 22455370
Breast cancer; Stage at diagnosis; Area-based socioeconomic status; Nation-wide; Multi-center; Retrospective study
11.  A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china 
BMC Cancer  2011;11:364.
According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.
This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.
Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).
The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.
PMCID: PMC3178543  PMID: 21859480

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