This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach. We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies. Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.

Mucinous carcinoma of the breast is a specific good prognostic type malignancy occurring in elderly patients. Neuroendocrine differentiation has long been described in mucinous carcinoma, but the significance of such finding is uncertain. We evaluated the neuroendocrine differentiation profiles of 38 cases of pure mucinous carcinoma and compared the clinicopathological differences between those with and those without neuroendocrine differentiation. The parameters assessed included patients' age, tumor size, nuclear grade, axillary lymph node status at time of diagnosis, percentage area of intratumoral mucin, and the expression of estrogen and progesterone receptors, cerbB2 oncoprotein, and three neuroendocrine markers, namely neurone-specific enolase, chromogranin, and synaptophysin by immunohistochemistry. Patients' outcome and follow-up period were also documented. Of the 38 cases of pure mucinous carcinoma, 28, 11 and six cases showed positive staining for 1, 2 and 3 of the neuroendocrine markers. For all the groups with variable neuroendocrine differentiation and compared to those without such differentiation, they all showed older patients' age, higher proportion of tumors with lower nuclear grade, lower incidence of axillary lymph node metastasis, a higher progesterone receptor, and lower cerbB2 oncoprotein expression. No difference was detected between tumor size, intratumoral mucinous area, and estrogen receptor status. In all, 37 patients did not have distant metastases or local recurrences at the end of follow-up period, while one patient with coexisting high-grade ductal carcinoma in situ at time of diagnosis died of breast carcinoma. Our findings suggest that the identification of neuroendocrine differentiation in pure mucinous carcinoma is associated with more favorable histologic and immunohistochemical parameters.

Breast cancers related to BRCA mutations are associated with particular biological features. Here we report the clinical and pathological characteristics of breast cancer in Chinese women with and without BRCA mutations and of carriers of BRCA1 mutations compared to BRCA2 mutations. Two hundred and 26 high-risk Hong Kong Chinese women were tested for BRCA mutations, medical information was obtained from medical records, and risk and demographic information was obtained from personal interviews. In this cohort, 28 (12.4%) women were BRCA mutation carriers and among these carriers, 39.3% were BRCA1 and 60.7% were BRCA2 mutations. Mutation carriers were more likely to have a familial history of breast and ovarian cancer, high-grade cancers, and triple negative (TN) cancers. Prevalence of TN was 48.3% in BRCA carriers and 25.6% in non-carriers and was 67.7% in BRCA1 and 35.3% in BRCA2 carriers. Estrogen receptor (ER) negative cancer was significantly associated with BRCA1 mutations, especially in those under 40 years of age. BRCA-related breast cancer in this Chinese population is associated with family history and adverse pathological/prognostic features, with BRCA2 mutations being more prevalent but BRCA1 carriers having more aggressive and TN cancers. Compared to Caucasian populations, prevalence of BRCA2 mutations and TN cancer in BRCA2 mutation carriers in Chinese population are elevated.

BackgroundHeterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European populations. Here, we aimed at characterizing the immune gene expression profile of luminal BC in an Asian population and associating it with patient characteristics and tumor genomic features.MethodsWe performed immune gene expression profiling of tumor and adjacent normal tissue in 92 luminal BC patients from Hong Kong using RNA-sequencing data and used unsupervised consensus clustering to stratify tumors. We then used luminal patients from The Cancer Genome Atlas (TCGA, N = 564) and a Korean breast cancer study (KBC, N = 112) as replication datasets.ResultsBased on the expression of 130 immune-related genes, luminal tumors were stratified into three distinct immune subtypes. Tumors in one subtype showed higher level of tumor-infiltrating lymphocytes (TILs), characterized by T cell gene activation, higher expression of immune checkpoint genes, higher nonsynonymous mutation burden, and higher APOBEC-signature mutations, compared with other luminal tumors. The high-TIL subtype was also associated with lower ESR1/ESR2 expression ratio and increasing body mass index. The comparison of the immune profile in tumor and matched normal tissue suggested a tumor-derived activation of specific immune responses, which was only seen in high-TIL patients. Tumors in a second subtype were characterized by increased expression of interferon-stimulated genes and enrichment for TP53 somatic mutations. The presence of three immune subtypes within luminal BC was replicated in TCGA and KBC, although the pattern was more similar in Asian populations. The germline APOBEC3B deletion polymorphism, which is prevalent in East Asian populations and was previously linked to immune activation, was not associated with immune subtypes in our study. This result does not support the hypothesis that the germline APOBEC3B deletion polymorphism is the driving force for immune activation in breast tumors in Asian populations.ConclusionOur findings suggest that immune gene expression and associated genomic features could be useful to further stratify luminal BC beyond the current luminal A/B classification and a subset of luminal BC patients may benefit from checkpoint immunotherapy, at least in Asian populations.