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Background: Survival rates of breast cancer patients are high, and the majority of women is Methods: We conducted a cross-sectional, hospital-based monocentric questionnaire study of women diagnosed with breast cancer. Recruitment was carried out from January to March 2011 for women diagnosed with and treated for primary breast cancer between 2005 and 2010 at Charité University Hospital Berlin. Results: The study included 492 breast cancer patients without recurrence. In total, 81.3% of the women returned to work, and 30.2% of the women felt a reduction of financial opportunities. Financial problems were named by at least 20% of the patients as being the main cause for a reduced quality of life. Conclusion: Long-term, disease-free breast cancer survivors reported a significant change in their work-related factors as well as changes in their financial opportunities.

Introduction The assessment of papillary lesions continues to be a challenging area in breast radiology and pathology. The management of intraductal papillomas without atypia of the breast remains controversial. The purpose of the present study was to determine diagnostic accuracy of radiographical diagnosis, core biopsy, and surgical excision in papillary breast lesions. Material and methods By using files from 1995 to 2010, 151 cases of intraductal papilloma with or without atypia were identified. Patients were stratified as follows: core biopsy followed by surgical excision (n = 61), core biopsy alone (n = 19), and surgical excision alone (n = 71). Results The upstage rate of intraductal papillomas without atypia on core biopsy to atypia or malignancy on excision was 8.9%. Excision specimens revealed intraductal papillomas without atypia in 68 out of 71 cases, and atypical papillomas in 3 cases. Conclusion Our findings suggest that radiographic and histopathological diagnosis of intraductal papillomas show high accuracy and good concordance. In cases where the radiographic diagnosis reveals suspicious lesions core biopsy represents the first choice.

Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor–negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid–like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element–binding protein cleavage–activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone–responsive protein)] indicated that silencing of multiple lipid metabolism–regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment. Cancer Res; 71(9); 3236–45. ©2011 AACR.

Purpose. Core biopsy is considered to be a highly accurate method for gaining preoperative diagnosis of breast cancer. The purpose of this study is to compare the results of core biopsy with those of the surgical excision specimen. Experimental design. A total of 567 core biopsies with subsequent surgical excision were performed. Results. In 488 patients, invasive breast cancer was diagnosed in the preoperative biopsy and in 486 patients (99.6%) the surgical specimen showed identical results. In 160 of the 502 patients (32%) with invasive breast cancer, DCIS was found in the surgical specimen but was not diagnosed in the biopsy. Estrogen and progesterone receptor demonstrated a high rate of agreement, Her2/neu analysis showed a complete concordance in 54% of patients. Conclusions. Core biopsies allow diagnosis of invasive breast cancer with high accuracy. Levels of agreement have to be improved for the detection of DCIS and Her2/neu status.

Molecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER−) breast cancer tissues were investigated using GC–TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2/3 of tumors) and could be validated in a predefined validation set (1/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER− subtype. Beta-alanine demonstrated the strongest change between ER− and ER+ breast cancer (fold change = 2.4, p = 1.5E − 20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R = − 0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER− breast cancer. In a Kaplan–Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR = 0.6, p=3.2E-15).Biological significanceIt is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER− breast as different diseases requiring different treatment strategies.Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER− breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER− subtype as a preferential target for glutaminase inhibitors.For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER− breast cancer.

Background Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. Results A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%. Conclusions For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

International audience; Neuroendocrine breast carcinomas are rare but may represent either metastatic or primary lesions. So far, clinical and preoperative histopathological examinations do not distinguish properly between a primary or metastatic breast tumor. Due to any possible consequences following an appropriate treatment, markers which may be helpful for such a distinguishment are needed. We addressed this study in order to evaluate the immunohistochemical expression of GCDFP-15 and mammaglobin in a subset of pure neuroendocrine breast carcinomas ( = 9) and compared the expression profile with a cohort of non-mammary neuroendocrine tumors ( = 99). We observed in our study that solid neuroendocrine breast carcinomas are characterized by the expression of estrogen and progesterone receptors as well as GCDFP-15 and/or mammaglobin. GCDFP-15 was expressed in 6 out of 9 cases, mammaglobin was positive in 4 out of 9 tumors. In contrast, neuroendocrine tumors of the non-mammary cohort expressed neither GCDFP-15 nor mammaglobin. We conclude that mammaglobin and GCDFP-15 as markers of epithelial breast origin may work as a new and reliable diagnostic tool to distinguish primary endocrine tumors of the breast from a metastatic neuroendocrine disease. This is of utmost importance, especially for surgical management.

The validated EndoPredict assay is a novel tool to predict the risk of metastases of patients with estrogen receptor positive, HER2 negative breast cancer treated with endocrine therapy alone. It has been designed to integrate genomic and clinical information and includes clinico-pathological factors such as tumor size and nodal status. The test is feasible in a decentral setting in molecular pathology laboratories. In this project, we investigated the performance of this test in clinical practice, and performed a retrospective evaluation of its impact on treatment decisions in breast cancer. During one year, EndoPredict assays from 167 patients could be successfully performed. For retrospective evaluation of treatment decisions, a questionnaire was sent to the clinical partner. Regarding the molecular EP class, samples from 56 patients (33.5%) had a low-risk, whereas 111 patients (66.5%) showed a high-risk gene profile. After integration of the clinicopathological factors the combined clinical and molecular score (EPclin) resulted in a low-risk group of 77 patients (46.4%), while 89 (53.6%) had a high risk EPclin score. The EPclin-based estimated median 10-year-risk for metastases with endocrine therapy alone was 11% for the whole cohort. The median handling time averaged three days (range: 0 to 11 days), 59.3% of the tests could be performed in three or less than three days. Comparison of pre- and post-test therapy decisions showed a change of therapy in 37.7% of patients. 16 patients (12.3%) had a change to an additional chemotherapy while 25.4% of patients (n = 33) changed to an endocrine therapy alone. In 73 patients (56.2%) no change of therapy resulted. In 6.1% of patients (n = 8), the patients did not agree to the recommendation of the tumor board. Our results show that the EndoPredict assay could be routinely performed in decentral molecular pathology laboratories and the results markedly change treatment decisions.