MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes.

Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony-forming ability and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

Gene expression in triple-negative breast cancer in relation to survival.

PURPOSE: The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. METHODS: We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. RESULTS: Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. CONCLUSIONS: We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Body mass index and weight change in relation to triple-negative breast cancer survival.

The aim of this study was to evaluate the influence of body mass index (BMI), weight change on triple-negative breast cancer (TNBC) prognosis in a population-based prospective cohort study. The current analysis included 518 participants diagnosed with TNBC in Shanghai Breast Cancer Survival Study. Weight at 1 year prior to cancer diagnosis, at diagnosis, and at 6, 18 and 36 months after cancer diagnosis and height at 6 months after cancer diagnosis were assessed. Disease-free survival (DFS) and overall survival (OS) were evaluated in relation to BMI and weight change using Cox proportional hazard models. Obesity (BMI ≥ 28.0 kg/m(2)) at 1-year pre-diagnosis was associated with higher risk of total mortality and recurrence/disease-specific mortality, with multivariate hazard ratios (HRs) of 1.79 (95 % CI 1.06-3.03) and 1.83 (95 % CI 1.05-3.21), respectively. The associations between BMI and TNBC prognosis attenuated over time from pre-diagnosis to post-diagnosis. Compared with stable weight (change within 5 %), weight loss ≥5 % at 18- or 36-month post-diagnosis was related with higher risk of total mortality and recurrence/disease-specific mortality. Respective multivariate HRs were 2.08 (95 % CI 1.25-3.46) and 1.42 (95 % CI 0.77-2.63) for OS, and 2.50 (95 % CI 1.45-4.30) and 2.17 (95 % CI 1.14-4.12) for DFS. However, the association of weight loss and OS/DFS attenuated after excluding patients whose weight was measured after recurrence. Weight gain ≥5 % at 18- or 36-month post-diagnosis was associated with a non-significant increased risk of death. The results showed that obesity pre-diagnosis and weight loss post-diagnosis was inversely associated with TNBC prognosis. Emphasis on maintaining stable weight after cancer diagnosis for TNBC patients may be considered.

Cancer incidence in urban Shanghai, 1973-2010: an updated trend and age-period-cohort effects.

BACKGROUND: To provide a comprehensive overview of temporal trends in cancer incidence during 1973-2010 in urban Shanghai. METHODS: The estimated annual percent changes (EAPCs) for the whole period and for the time segments in age-standardized incidence rates (ASR) were evaluated with Joinpoint analysis. Age-period-cohort (APC) models were modeled to examine the effects of age, period and birth cohort on cancer incidence. RESULTS: The overall ASR decreased slightly and significantly in males (EAPC of -0.41) but increased significantly in females (EAPC of 0.57) during 1973-2010 in urban Shanghai. The incidence trend was not linear and varied by time segments. During the most recent 10 years (2001-2010), the ASR in males decreased by 1.65% per year and stabilized in females. Incidence rates continued to decline during 1973-2010 for esophagus, stomach, and liver cancer in both sexes, as well as male lung cancer and cervix cancer. It should be noted that it was the first time to document a significant decline in lung cancer incidence among males during 1973-2010 with EAPC of -0.58%, and a notable upward for cervix cancer since 1996 with EAPC of 8.94%. Unfavorable trends in incidence were observed for the most common cancer sites in the 38 years period: colorectum, gallbladder & biliary tract, pancreas, kidney, bladder, brain & central nervous system (CNS), thyroid, non-Hodgkin's lymphoma (NHL), prostate, female breast, corpus uteri, and ovary. APC analysis showed age, period and birth cohort yielded different effects by cancer sites. CONCLUSIONS: The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyles in urban Shanghai over the past four decades.

Tumor tissue microRNA expression in association with triple-negative breast cancer outcomes.

We evaluated suggested metastasis-related microRNAs (miRNAs) for their associations with disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer (TNBC). In a cohort of 456 TNBC cases, we systematically evaluated 57 previously reported metastasis-related miRNAs in tumor tissue using the NanoString nCounter assay. Cox regression was applied to evaluate miRNA expression in association with DFS and OS. In vitro assays using the TNBC cell line MDA-MB-231 were also conducted to validate epidemiological study findings. During a median follow-up of 5.3 years, 112 deaths and 97 recurrences were documented. High levels of miR-374b-5p, miR-218-5p, or miR-126-3p, or low levels of miR-27b-3p were independently associated with a favorable TNBC outcome (P < 0.01 for all). A composite score based on the levels of these four miRNAs was associated with DFS, with hazard ratios (95 % confidence interval) of 0.70 (0.43-1.15), 0.51 (0.29-0.90), and 0.18 (0.09-0.37) for the second, third, and fourth compared to the lowest quartile. Incorporating the miRNA score with known TNBC outcome predictors, i.e., age at diagnosis, tumor stage, and basal-like subtype, increased the C-index for predicting DFS from 0.68 to 0.74. Additionally, miR-126-3p was correlated with basal-like breast cancer, and miR-374b-5p modified the therapeutic effects of 5-Fluorouracil and Cyclophosphamide treatments in basal-like breast cancer patients. Restoring miR-126-3p, miR-218-5p, or miR-374b-5p, or inhibiting miR-27b-3p in MDA-MB-231 cells reduced cell proliferation. miR-374b-5p suppressed cell invasion and miR-218-5p inhibited colonization. This study provides strong evidence that the expression levels of miR-374b-5p, miR-27b-3p, miR-126-3p, and miR-218-5p in tumor tissues predict TNBC outcomes.

Soy isoflavone intake and bone mineral density in breast cancer survivors.

PURPOSE: Low bone mineral density (BMD) is common among breast cancer survivors due to acute estrogen deprivation. Soy food is a rich source of phytoestrogens, namely isoflavones, known to have both estrogenic and anti-estrogenic effects. The objective of the study was to assess the association between soy consumption and BMD in breast cancer survivors, which has not previously been evaluated. METHODS: Forearm BMD was evaluated using dual-energy X-ray absorptiometry at 60 months post-diagnosis for 1,587 participants of the Shanghai Breast Cancer Survival Study. Soy intakes collected at 6, 18, and 36 months post-diagnosis were averaged, and the association with BMD, osteopenia, and osteoporosis was evaluated using linear and logistic regression. RESULTS: The mean (standard deviation) intake of isoflavones was 48.1 (28.0) mg/day. Soy intake was inversely associated with BMD and positively associated with osteoporosis. Compared with the lowest quartile, the highest quartile of soy isoflavone intake, ≥ 62.64 mg/day, was associated with a reduction of BMD by 1.95% [95% confidence interval (CI) -3.54, -0.36%] and an increased odds ratio of 1.69 for osteoporosis (95% CI 1.09, 2.61). The inverse association was predominantly seen among women who recently entered menopause (≤ 5 years). CONCLUSION: In contrast to observations from general populations, high soy intake (≥ 62.64 mg of soy isoflavone/day) was associated with lower proximal forearm BMD among breast cancer survivors, particularly during the early years of menopause. Our finding needs to be replicated, particularly in studies with more comprehensive bone density evaluation.

Modifiable Lifestyle Factors and Triple-negative Breast Cancer Survival: A Population-based Prospective Study.

BACKGROUND: Very little is known about the effect of modifiable lifestyle factors on outcomes of triple-negative breast cancer. We examined this association in a population-based prospective cohort study of patients with triple-negative breast cancer. METHODS: A total of 518 women with confirmed triple-negative breast cancer, recruited by the Shanghai Breast Cancer Survival Study, completed 6-, 18-, 36-, and 60-month postdiagnosis surveys. We applied Cox proportional hazard models to evaluate the associations. RESULTS: The mean age at diagnosis was 53.4 (standard deviation = 10.6) years old. After a median follow-up of 9.1 years (range: 0.6-11.8), 128 deaths and 112 recurrences were documented. Exercise during the first 60 months postdiagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with adjusted hazard ratios (HRs) of 0.67 (95% confidence interval [CI] = 0.46, 0.96) and 0.58 (95% CI = 0.39, 0.86), respectively. Women with higher exercise-metabolic equivalent scores (≥7.6 metabolic equivalent-hours/week) and longer duration of exercise (≥2.5 hours/week) had lower risk of total and recurrence/disease-specific mortality than did nonexercisers. Compared with nontea drinkers, survival was better among women who were regular tea drinkers during the first 60 months for all cause (HR = 0.57, 95% CI = 0.34, 0.93) and recurrence/disease-specific mortality (HR = 0.54, 95% CI = 0.31, 0.96). There was no dose-response pattern for tea consumption. No interactions were observed for body mass index, menopausal status, and comorbidity. CONCLUSIONS: These findings show that postdiagnosis exercise and tea intake were associated with improved survival among women with triple-negative breast cancer.

Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome.

Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20-75 years who participated in the Shanghai Breast Cancer Survival Study, and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r = 0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95 % confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95 % CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.

Comorbidities and breast cancer survival: a report from the Shanghai Breast Cancer Survival Study.

We investigated the association of major comorbidities with breast cancer outcomes using the Shanghai Breast Cancer Survival Study, a population-based, prospective cohort study of Chinese women diagnosed with breast cancer. Analyses included 4,664 women diagnosed with stage I-III incident breast cancer aged 20-75 years (median age = 51) during 2002-2006. Women were interviewed at 3-11 months post-diagnosis (median = 6.4) and followed up by in-person interviews and linkage with the vital statistics registry. Multivariable hazard ratios (HRs) and (95 % confidence intervals (CIs)) for the associations of comorbidities with breast cancer outcomes were estimated using Cox regression models. After a median follow-up of 5.3 years (range: 0.64-8.9), 647 women died (516 from breast cancer) and 632 recurrence/metastases were documented. The main comorbidities reported included: hypertension (22.4 %), chronic gastritis (14.3 %), diabetes mellitus (6.2 %), chronic bronchitis/asthma (5.8 %), coronary heart disease (5.0 %), and stroke (2.2 %). Diabetes was associated with increased risk of total mortality (adjusted HR: 1.40 (1.06-1.85)) and non-breast cancer mortality (adjusted HR: 2.64 (1.63-4.27)), but not breast cancer-specific mortality (adjusted HR: 0.98 (0.68-1.41)), adjusting for socio-demographics, clinical characteristics, selected lifestyle factors, and other comorbidities. Women with a history of stroke had a non-significant increased risk of total mortality (adjusted HR: 1.42 (0.91-2.22)) and a significant increased risk of non-breast cancer mortality (adjusted HR: 2.52 (1.33-4.78)), but not breast cancer-specific mortality (adjusted HR: 0.78 (0.38-1.62)). Overall, none of the comorbidities investigated were significantly associated with recurrence. In this large prospective cohort of breast cancer survivors, diabetes was significantly associated with increased risk of total and non-breast cancer mortality, and history of stroke was associated with increased risk of non-breast cancer mortality.

Exercise after diagnosis and metabolic syndrome among breast cancer survivors: a report from the Shanghai Breast Cancer Survival Study.

Metabolic syndrome (MetS) is an established risk factor for cardiovascular diseases and mortality. Limited data are available on the prevalence of MetS and its association with exercise among breast cancer survivors. The present study included 1,696 breast cancer survivors from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study conducted between April 2002 and October 2011 in Shanghai, China. All women had a physical examination taken at study clinic approximately 60 months post-diagnosis. Exercise was assessed at approximately 6, 18, 36, and 60 months post-diagnosis. Information on medical history, tumor characteristics, cancer treatment, anthropometrics, and lifestyle was collected at study enrollment. Associations between exercise and MetS at 60 months post-diagnosis were evaluated with multivariable logistic regression models. The mean age of the study population was 56.68 at 60-month survey, and the mean follow-up since cancer diagnosis was 63.66 months. The prevalence of MetS using National Cholesterol Education Program Adult Treatment Panel III criteria at approximately 60 months after diagnosis was 33.14%. Among overweight and obesity breast cancer survivors (body mass index (BMI) ≥ 25 kg/m(2) at baseline), the prevalence was 55.18%. The most common type of exercise in this population was walking (45.40%) at baseline. Exercise participation between 6 and 60 months post-diagnosis was inversely associated with the prevalence of MetS with the adjusted odds ratio (OR) for exercise participation of ≥ 3.5 h/week (30 min/day) being 0.69 (95% confidence interval (CI) 0.48-0.98). In addition consistent exercise participation reduced the prevalence of MetS (adjusted OR 0.70 (95% CI 0.50-1.00). Associations of exercise with MetS were not modified by baseline waist circumference, BMI, comorbidity, baseline menopausal status, TNM stage, cancer treatment, or ER/PR status (p interactions > 0.05). Regular and persistent exercise after cancer diagnosis, even at low-to-moderate intensity level, decreases the prevalence of MetS among long-term breast cancer survivors.

Fruit, vegetable, and animal food intake and breast cancer risk by hormone receptor status.

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996-1998 (phase I) and 2002-2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67-0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status.

Population-based survival for childhood cancer patients diagnosed during 2002-2005 in Shanghai, China.

BACKGROUND: There have been no population-based studies on cancer survival among children aged 0-14 years in China. In this study, we aimed to characterize the cancer survival among children in Shanghai. PROCEDURE: Childhood cancer cases registered by the Shanghai Cancer Registry between 2002 and 2005 and enrolled in the Shanghai Childhood Survival Study were included in this study. We used Kaplan-Meier product-limit method for survival analysis and Cox proportional hazards models for investigating the effects of various prognostic factors. RESULTS: The median follow-up time was 5.4 years (range 0-8.9 years). The 5-year observed survival for all childhood cancers combined was 55.7% (95% CI: 51.7-59.6%). For leukemia, lymphoma, and central nervous system tumors, the three most common types of childhood cancer, 5-year survival rates were 52.2%, 58.8%, and 41.2%, respectively. Higher 5-year survival rates were observed for epithelial cancer (88.9%), malignant renal tumors (86.7%), germ cell and other gonadal tumors (78.4%), and retinoblastoma (75.0%). Cancers with poor prognosis included sympathetic nervous system tumors (57.9%), soft tissue sarcoma (54.1%), bone tumors (52.6%), and liver cancer (33.3%). There were no significant differences between survival rates by gender and age groups. Compared with those reported in the USA and Europe, the survival rates for all cancers combined and the three most common types in Shanghai were lower. CONCLUSIONS: The survival rate for children aged 0-14 diagnosed with cancer in Shanghai during 2002-2005 was at the medium level. There was a substantial survival difference from childhood cancers between Shanghai and specific developed countries.

Improved risk scoring systems for colorectal cancer screening in Shanghai, China.

BACKGROUND: An optimal risk-scoring system enables more targeted offers for colonoscopy in colorectal cancer (CRC) screening. This analysis aims to develop and validate scoring systems using parametric and non-parametric methods for average-risk populations. METHODS: Screening data of 807,695 subjects and 2806 detected cases in the first-round CRC screening program in Shanghai were used to develop risk-predictive models and scoring systems using logistic-regression (LR) and artificial-neural-network (ANN) methods. Performance of established scoring systems was evaluated using area under the receiver operating characteristic curve (AUC), calibration, sensitivity, specificity, number of high-risk individuals and potential detection rates of CRC. RESULTS: Age, sex, CRC in first-degree relatives, chronic diarrhoea, mucus or bloody stool, history of any cancer and faecal-immunochemical-test (FIT) results were identified as predictors for the presence of CRC. The AUC of LR-based system was 0.642 when using risk factors only in derivation set, and increased to 0.774 by further incorporating one-sample FIT results, and to 0.808 by including two-sample FIT results, while those for ANN-based systems were 0.639, 0.763 and 0.805, respectively. Better calibrations were observed for the LR-based systems than the ANN-based ones. Compared with the currently used initial tests, parallel use of FIT with LR-based systems resulted in improved specificities, less demands for colonoscopy and higher detection rates of CRC, while parallel use of FIT with ANN-based systems had higher sensitivities; incorporating FIT in the scoring systems further increased specificities, decreased colonoscopy demands and improved detection rates of CRC. CONCLUSIONS: Our results indicate the potentials of LR-based scoring systems incorporating one- or two-sample FIT results for CRC mass screening. External validation is warranted for scaling-up implementation in the Chinese population.

UACA locus is associated with breast cancer chemoresistance and survival.

Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ([Formula: see text]). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, [Formula: see text]). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ([Formula: see text]). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.

Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women.

The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996-1998 and 2002-2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women.

Association of hormone-related characteristics and breast cancer risk by estrogen receptor/progesterone receptor status in the shanghai breast cancer study.

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER-)/PR-negative (PR-) cases, 301 ER+/PR- cases, 254 ER-/PR+ cases, and 3,474 controls aged 20-70 years in Shanghai, China (phase I, 1996-1998; phase II, 2002-2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)(2)) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER-/PR- subtype (for parity, P(heterogeneity) = 0.02; for BMI, P(heterogeneity) < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR- subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR- tumors and ER-/PR+ tumors.

Trends in childhood cancer incidence and mortality in urban Shanghai, 1973-2005.

BACKGROUND: To describe trends in cancer incidence and mortality among children less than 15 years of age in urban Shanghai between 1973 and 2005. PROCEDURE: Annual rates of cancer incidence were calculated per 1,000,000 children for 3-year intervals between 1973 and 2005. Linear regression models were used to analyze the annual percent change (APC) in incidence and mortality across these distinct intervals. RESULTS: For all cancers combined, the incidence rate during the observed time period did not substantially change in urban Shanghai. Rates for the incidence of individual cancer did exhibit variations. Leukemia incidence remained relatively stable but the incidence of myeloid leukemia decreased sharply in both males (APC -8.6%) and females (APC -9.5%). The rate of NHL varied little among males with APC 2.1% and modestly increased among females with APC 9.3%. Anatomic sites that only occasionally demonstrate malignancy, bone and joints in males and endocrines in females, showed upward trends in incidence. A significant reduction in liver cancer incidence in males was observed. Examining mortality rates, all cancer mortality decreased by -6.0% annually in males and by -3.9% in females. This trend was mainly due to the reduction in mortality for leukemia, particularly the myeloid subtype, which decreased in males (APC -7.2%) and females (APC -7.3%). CONCLUSIONS: Childhood cancer incidence rates showed no substantial changes but mortality demonstrated a dramatic reduction during the observed time period, suggesting an improvement in both childhood cancer diagnosis and treatment.

Time trends and characteristics of childhood cancer among children age 0-14 in Shanghai.

BACKGROUND: The aim of this article is to analyze the time trends during 1973-2005 in urban Shanghai and to describe the current characteristics of childhood cancer in Shanghai. PROCEDURE: All data were from the Shanghai Cancer Registry. Time trends of period 1973-2005 in urban Shanghai of males and females were assessed by annual percentage change of incidence. The current characteristics of Shanghai childhood cancer average annual incidence were analyzed regarding sex, age, and cancer types. All cancers were allocated into 12 major groupings of ICCC. RESULTS: Over the 33-year period, the overall age-standardized incidence rate for all cancers combined has no substantial change or trend in urban Shanghai aged 0-14. A total of 609 cases of childhood cancer were diagnosed in Shanghai from 2002 to 2005. The ASR of 2002-2005 is 129.0 per million for all cancers combined, and it was almost similar in males (128.5 per million) and in females (129.6 per million). Incidence rates are highest in the first 5 years of life with 173.3 per million. Leukaemia was the most common cancer (34.5%). Brain and spinal tumour was the second most common cancer (20.2%), followed by lymphomas (8.4%). The relative frequencies of Wilms tumour (2.0%) and Ewing sarcoma (0.5%) were lower than those reported from western countries. CONCLUSION: During 1973-2005, the trend of childhood cancer incidence in urban Shanghai has shown no significant change. Incidence of childhood cancers in Shanghai was in the medium level compared to other parts of the world and the relative frequencies of various cancers were comparable.

Soy Food Consumption, Exercise, and Body Mass Index and Osteoporotic Fracture Risk Among Breast Cancer Survivors: The Shanghai Breast Cancer Survival Study.

BACKGROUND: Breast cancer survivors have a high incidence of osteoporosis-related fractures; the associated factors are understudied. We investigated incidence of bone fracture and its associations with soy food consumption, exercise, and body mass index among breast cancer survivors. METHODS: This prospective study included 4139 stage 0-III breast cancer patients and 1987 pre-/perimenopausal and 2152 postmenopausal patients. Fractures were assessed at 18 months and at 3, 5, and 10 years after cancer diagnosis. Osteoporotic fractures were defined as fractures caused by falls from standing height and at sites associated with osteoporosis. Exercise and soy isoflavone intake were assessed at 6 and 18 months postdiagnosis. Weight and height were measured at baseline. Lifetable and Cox regression analyses were employed. All statistical tests were two sided. RESULTS: The 10-year incidence for osteoporotic fractures was 2.9% and 4.4% for pre-/perimenopausal and postmenopausal patients, respectively. High soy isoflavone intake was associated with reduced risk among pre-/perimenopausal patients (hazard ratio [HR] = 0.22, 95% confidence interval [CI] = 0.09 to 0.53, for soy isoflavone mg/d ≥56.06 vs <31.31; P trend < .001) but not among postmenopausal patients (P interaction < .01). Overweight (vs normal weight) was a risk factor for pre-/perimenopausal patients (HR = 1.81, 95% CI = 1.04 to 3.14) but not for postmenopausal patients (HR = 0.67, 95% CI = 0.43 to 1.03; P interaction = .01). Exercise was inversely associated with osteoporotic fractures in postmenopausal patients (HR = 0.56, 95% CI = 0.33 to 0.97, for metabolic equivalents hours ≥12.6 vs <4.5) following a dose-response pattern (P trend = .035), an association not modified by menopausal status. CONCLUSIONS: Our findings, especially the novel association of soy food intake with osteoporotic fractures in breast cancer survivors, if confirmed, can help guide future strategies for fracture risk reduction in this vulnerable population.

ALDH1A1 mRNA expression in association with prognosis of triple-negative breast cancer.

ALDH1 is a crucial element in the retinoic acid signaling pathway regulating the self-renewal and differentiation of normal stem cells, and may play an important role in cancer progression. However, research on ALDH1 gene expression and breast cancer prognosis has yielded conflicting results. We evaluated the association between tumor tissue ALDH1A1/ALDH1A3 mRNA expression and triple-negative breast cancer (TNBC) prognosis in the Shanghai Breast Cancer Survival Study (SBCSS, N=463), Nashville Breast Health Study (NBHS, N=86), and Southern Community Cohort Study (SCCS, N=47). Gene expression was measured in RNA isolated from breast cancer tissues. In the SBCSS, higher ALDH1A1 mRNA level was associated with improved disease-free (HR=0.87, 95% CI: 0.80-0.95, per log unit change) and overall survival (HR=0.85, 95% CI: 0.78-0.93 per log unit change) independent of age at diagnosis, TNM stage and treatment. We replicated the findings for overall survival in the NBHS and SCCS (HR = 0.27, 95% CI: 0.10-0.73) and for disease-free survival by a meta-analysis of four publicly-available gene expression datasets (HR = 0.86, 95% CI: 0.76-0.97). No significant association was found for ALDH1A3.Our study suggests high expression of ALDH1A1 mRNA in tumor tissues may be an independent predictor of a favorable TNBC outcome.