Variability and stability of coping styles among breast cancer survivors: A prospective study.

OBJECTIVES: We aimed to examine: (1) the long-term association between coping styles and psychological distress, (2) if women diagnosed with breast cancer have a predominant coping style, (3) stability of coping styles, (4) predictors of changes in coping styles, (5) if maladaptive coping adversely impacts disease-free survival (DFS). METHODS: This prospective study included women diagnosed with primary breast cancer during 2006-2009. Patients completed questionnaires for the Norwegian Mini-Mental Adjustment to Cancer scale, which includes positive attitude (PA), helplessness/hopelessness (HH), anxious preoccupation (AP), and avoidance (AV), and the Hospital Anxiety and Depression Scale at diagnosis and 1, 3, and 5 years postdiagnosis. RESULTS: Two hundred and ninety-three of 367 women (79.8%) completed the questionnaires at all time points. Anxiety and depression were moderately to strongly correlated with HH and AP coping styles (r = 0.31 to r = 0.69) at all time points. The predominant coping style was PA (23.4-29.9%). Stability for PA and cognitive AV styles was found at the group level, but not at an individual level. Chemotherapy and comorbidity were predictors for HH, AP, and AV 5 years postdiagnosis (p < 0.05). Maladaptive coping was not associated with DFS. CONCLUSIONS: HH and AP were associated with higher psychological distress at all times. Group level coping remained stable over time for PA and AV. Coping style stability at an individual level was not observed. Having received chemotherapy and experienced adverse events affected coping at 5 years postdiagnosis. Maladaptive coping was not associated with DFS.

Using clinical cancer registry data for estimation of quality indicators: Results from the Norwegian breast cancer registry.

INTRODUCTION: Increased focus on quality indicators and the use of clinical registries for breast cancer for real world studies have shown higher compliance to recommended therapy and better survival. In 2010, the European Society of Breast Cancer Specialist (EUSOMA) proposed quality indicators (QI) covering diagnosis, treatment and follow-up. To become a EUSOMA certified Breast Cancer Unit, 14 specified quality indicators, in addition to other requirements, need to be met. To evaluate the compliance and results of recommended treatment in breast cancer care in Norway and to improve the quality of epidemiological data, the Cancer Registry of Norway (CRN) in cooperation with the Norwegian Breast Cancer Group (NBCG) developed the Norwegian Breast Cancer Registry (NBCR). The objective of this study is to assess the feasibility of using the NBCR for estimating the EUSOMA QI individually for all hospitals diagnosing and treating breast cancer in Norway. METHODS: To provide researchers with high quality cancer data as well as for the purpose of national cancer statistics, the CRN employs a cancer registry system to 1) longitudinal capture data from all patients from all medical entities that diagnose and/or treat cancer patients (e.g., pathology, radiology and clinical departments) in Norway; 2) curate data, i.e. validate the correctness of collected data, and assemble the validated cancer data as cancer cases; 3) provide data for analytics and presentation. Estimates for 10 EUSOMA QI were calculated at national and hospital level. To compare hospitals, a summary score of QIs was defined for each hospital. RESULTS: All hospitals currently treating breast cancer patients have the technical ability to submit data to the NBCR for estimation of QIs defined by EUSOMA. Data from pathology and surgery are of high quality. However, data from oncological and radiological departments are incomplete, but improving. This currently hinders three QIs from being calculated. QI on benign to malign diagnosis needs to be calculated at the individual Breast Centre. Over time the adherence to guidelines have improved and the hospital variation for the respective QI have decreased. Two hospitals met all minimum standard on ten QIs in year 2016 and one hospital did not meet one minimum standard, but met all other targets. CONCLUSION: The NBCR has since 2012 published annual reports on breast cancer care and for the year 2016 measured 10 of 14 QI defined by EUSOMA. Increased compliance of recommended treatment in Norway has been observed during the years the registry has been active.

Better survival after breast-conserving therapy compared to mastectomy when axillary node status is positive in early-stage breast cancer: a registry-based follow-up study of 6387 Norwegian women participating in screening, primarily operated between 1998 and 2009.

BACKGROUND: Recent registry studies on early-stage breast cancer have shown better survival rates when women underwent breast-conserving therapy (BCT) compared with mastectomy (MTX). The aim of this study is to investigate women participating in screening, in all four stages of early breast cancer (T1N0M0, T2N0M0, T1N1M0, and T2N1M0), as to whether there is a survival benefit when women undergo BCT compared to MTX. METHOD: A cohort of 6387 women aged 50-69, with primary-operated breast cancer from January 1998 to December 2009, participating in screening and followed-up until the end of 2010. Life tables were calculated by stages (pT1N0M0, pT2N0M0, pT1N1M0, and pT2N1M0), surgery groups (BCT and MTX), and screening detection (first screening, later screening, or interval cancer). Cox regression was used to calculate hazard ratios (HR) between BCT and MTX in crude and adjusted analyses. RESULTS: In stage T1N1M0, women who underwent MTX had an HR of 2.91 (95% CI 1.30-6.48) for breast cancer death compared to women who underwent BCT, after adjusting for screening detection, years of diagnosis, age at diagnosis, histology, grade, and hormone receptor status. For all other TNM categories of early breast cancer, there was no difference in survival. 10-year breast cancer-specific survival (BCSS) in T1N0M0 was 98% for women undergoing BCT and 96% for women undergoing MTX. 10-year BCSS in T1N1M0 was 97% for women undergoing BCT and 89% for women undergoing MTX. CONCLUSIONS: For women participating in screening, there is a benefit of BCT over MTX in stage T1N1M0. No such effects were observed in the other early stages of breast cancer.

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome.

BACKGROUND: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. METHODS: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. RESULTS: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. CONCLUSIONS: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.

The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer.

WRAP53 protein controls intracellular trafficking of DNA repair proteins, the telomerase enzyme, and splicing factors. Functional loss of the protein has been linked to carcinogenesis, premature aging and neurodegeneration. The aim of this study was to investigate the prognostic significance of WRAP53 protein expression in breast cancer. A tissue microarray was constructed from primary breast tumors and immunostained by a polyclonal WRAP53 antibody to assess the protein expression pattern. Two different patient cohorts with long term follow-up were studied; a test- and a validation set of 154 and 668 breast tumor samples respectively. Breast cancer patients with tumor cells lacking the expression of WRAP53 in the nucleus had a significantly poorer outcome compared to patients with tumor cells expressing this protein in the nuclei (HR = 1.95, 95%CI = 1.09-3.51, p = 0.025). Nuclear localization of WRAP53 was further shown to be an independent marker of prognosis in multivariate analysis (HR = 2.57, 95%CI = 1.27-5.19, p = 0.008), and also significantly associated with better outcome in patients with TP53 mutation. Here we show that the sub-cellular localization of the WRAP53 protein has a significant impact on breast cancer survival, and thus has a potential as a clinical marker in diagnostics and treatment.

Integrated analysis reveals microRNA networks coordinately expressed with key proteins in breast cancer.

BACKGROUND: The role played by microRNAs in the deregulation of protein expression in breast cancer is only partly understood. To gain insight, the combined effect of microRNA and mRNA expression on protein expression was investigated in three independent data sets. METHODS: Protein expression was modeled as a multilinear function of powers of mRNA and microRNA expression. The model was first applied to mRNA and protein expression for 105 selected cancer-associated genes and to genome-wide microRNA expression from 283 breast tumors. The model considered both the effect of one microRNA at a time and all microRNAs combined. In the latter case the Lasso penalized regression method was applied to detect the simultaneous effect of multiple microRNAs. RESULTS: An interactome map for breast cancer representing all direct and indirect associations between the expression of microRNAs and proteins was derived. A pattern of extensive coordination between microRNA and protein expression in breast cancer emerges, with multiple clusters of microRNAs being associated with multiple clusters of proteins. Results were subsequently validated in two independent breast cancer data sets. A number of the microRNA-protein associations were functionally validated in a breast cancer cell line. CONCLUSIONS: A comprehensive map is derived for the co-expression in breast cancer of microRNAs and 105 proteins with known roles in cancer, after filtering out the in-cis effect of mRNA expression. The analysis suggests that group action by several microRNAs to deregulate the expression of proteins is a common modus operandi in breast cancer.

Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF.

INTRODUCTION: Hypercoagulability in malignancy increases the risk of thrombosis, but is also involved in cancer progression. Experimental studies suggest that tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are involved in cancer biology as a tumor- promoter and suppressor, respectively, but the clinical significance is less clear. Here, we aimed to investigate the clinical relevance of TF and TFPI genetic and phenotypic diversity in breast cancer. METHODS: The relationship between tumor messenger RNA (mRNA) expression and plasma levels of TF and TFPI (α and ß), tagging single nucleotide polymorphisms (tagSNPs) in F3 (TF) (n=6) and TFPI (n=18), and clinicopathological characteristics and molecular tumor subtypes were explored in 152 treatment naive breast cancer patients. The effect of tumor expressed TF and TFPIα and TFPIß on survival was investigated in a merged breast cancer dataset of 1881 patients. RESULTS: Progesterone receptor negative patients had higher mRNA expression of total TFPI (α+ß) (P=0.021) and TFPIß (P=0.014) in tumors. TF mRNA expression was decreased in grade 3 tumors (P=0.003). In plasma, total TFPI levels were decreased in patients with larger tumors (P=0.013). SNP haplotypes of TFPI, but not TF, were associated with specific clinicopathological characteristics like tumor size (odds ratio (OR) 3.14, P=0.004), triple negativity (OR 2.4, P=0.004), lymph node spread (OR 3.34, P=0.006), and basal-like (OR 2.3, P=0.011) and luminal B (OR 3.5, P=0.005) molecular tumor subtypes. Increased expression levels of TFPIα and TFPIß in breast tumors were associated with better outcome in all tumor subtypes combined (P=0.007 and P=0.005) and in multiple subgroups, including lymph node positive subjects (P=0.006 and P=0.034). CONCLUSIONS: This study indicates that genetic and phenotypic variation of both TFPIα and TFPIß, more than TF, are markers of cancer progression. Together with the previously demonstrated tumor suppressor effects of TFPI, the beneficial effect of tumor expressed TFPI on survival, renders TFPI as a potential anticancer agent, and the clinical significance of TFPI in cancer deserves further investigation.

Survival is Better After Breast Conserving Therapy than Mastectomy for Early Stage Breast Cancer: A Registry-Based Follow-up Study of Norwegian Women Primary Operated Between 1998 and 2008.

BACKGROUND: Breast-conserving therapy (BCT) and mastectomy (MTX) has been considered to have a similar long-time survival. However, better survival in women undergoing BCT compared with MTX is found in two recent register studies from the United States. The purpose of this study was to compare survival after BCT and MTX for women with early-stage breast cancer in Norway. METHODS: Women with invasive, early-stage breast cancer (1998-2008) where BCT and MTX were considered as equally beneficial treatments were included for a total of 13,015 women. Surgery was divided in two main cohorts (primary BCT, primary MTX) and five subcohorts. Analyses were stratified into T1N0M0, T2N0M0, T1N1M0, T2N1M0, and age groups (<50, 50-69, ≥70). Overall survival and breast cancer-specific survival (BCSS) were calculated in life tables, hazard ratios by Cox regression, and sensitivity analyses. RESULTS: Five-year BCSS for women who underwent primary BCT or primary MTX was 97 and 88 %, respectively. Women who underwent primary MTX had a hazard ratio of 1.64 (95 % confidence interval 1.43-1.88) for breast cancer death compared with women who underwent primary BCT after adjusting for the year of diagnosis, age at diagnosis, stage, histology, and grade. CONCLUSIONS: Survival was better or equal after breast-conserving therapy than mastectomy in all early stages, surgical subcohorts, and age groups. This advantage could not only be attributed to differences in tumor biology.

Increased coagulation activity and genetic polymorphisms in the F5, F10 and EPCR genes are associated with breast cancer: a case-control study.

BACKGROUND: The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. METHODS: 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. RESULTS: Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95% CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95% CI 4.4-11.3), and high thrombin peak (OR 6.1, 95% CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95% CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95% CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. CONCLUSIONS: A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer.

The value of preoperative ultrasound guided fine-needle aspiration cytology of radiologically suspicious axillary lymph nodes in breast cancer.

BACKGROUND: Preoperative ultrasound (US) and eventually US-guided fine-needle aspiration cytology (FNAC) of suspicious axillary lymph nodes (ALN) is a standard procedure in the work-up of suspicious breast lesions. Preoperative US FNAC may prevent sentinel node biopsy (SNB) procedure in 24-30% of patients with early stage breast carcinoma. The aim of this study was to evaluate the institutional results of this preoperative diagnostic procedure. MATERIALS AND METHODS: A total of 182 cases of preoperative FNAC of suspicious ALN where retrieved from the pathology files. The results were compared with the final histology and staging. False negative (FN) FNAC cases were reviewed and possibly missed metastatic cases (2) were immunostained with the epithelial marker AE1/AE3. RESULTS: There were no false positives, whereas 16 cases were FN. In all but one case the FN's represented sampling error. Half of the 16 FN cases in this series were macrometastases. DISCUSSION: About 83% of the preoperatively aspirated cases were N+, indicating that a radiologically suspicious ALN has a very high risk of being metastatic. Preoperative US guided FNAC from radiologically suspicious ALN is highly efficient in detecting metastases. Depending on national guidelines, a preoperative, positive ALN FNAC might help to stratify the patients as to SNB and/or ALN dissection.

Effects of a psychoeducational versus a support group intervention in patients with early-stage breast cancer: results of a randomized controlled trial.

BACKGROUND: Limited documentation exists on the effectiveness of psychoeducational group (PEG) versus support group (SG) interventions among breast cancer patients during primary care. Support group is a component of the hospitals' routine breast cancer care. OBJECTIVE: The aim of this study was to investigate which of these approaches provides the greatest benefits to participants, particularly to women with low optimism (pessimists). The primary outcomes investigated here were anxiety, depression, and mental adjustment to cancer. METHODS: A total of 367 women with early-stage breast cancer were randomized to the PEG or SG intervention starting 1 to 8 weeks after surgery. The PEG intervention included health education, enhancement of problem-solving skills, stress management, and psychological support. RESULTS: Participants in both groups showed improvement over time; however, no significant differences in emotional distress were found. The PEG participants exhibited more positive attitude at 2 and 6 months (P < .001) and less helplessness/hopelessness (P = .01) at 2 months compared with the SG participants. However, no significant differences were found between the groups at 12 months. Pessimists did not benefit more from attending the PEG than they did from attending the SG. CONCLUSION: Both groups showed improvement in emotional distress and coping over time. Although the results were limited, the PEG intervention seems to enhance short-term, but not long-term, adaptive coping. IMPLICATIONS FOR PRACTICE: Psychoeducational group intervention yields benefits during the difficult period when patients receive adjuvant chemotherapy or radiotherapy. Thus, the hospital's standard group interventions have been changed to include more health education and stress management, but within the same time frame as the original SG.

[Breast cancer surgery in Norway 1986-2009]. / Brystkreftkirurgi i Norge 1986-2009.

BACKGROUND: Studies have revealed variations in breast cancer survival between different counties in Norway. This study describes trends in surgical treatment of ductal carcinoma in situ (DCIS) and breast cancer in Norway, over time and by county. MATERIAL AND METHOD: Information about surgical treatment, age and county for 3,915 women with DCIS and for 54,732 women with breast cancer, diagnosed in the periods 1995-2009 and 1986-2009 respectively, was provided from the incidence database at the Cancer Registry of Norway. RESULTS: In the period 1995-97, 3.0 in 100,000 women with DCIS had breast conserving treatment (BCT), while 5.0 in 100,000 had mastectomy. In 2004-06 the rates were 8.6 and 4.2, respectively. In 1995-97, 18.7 in 100,000 women with breast cancer had BCT, while 77.3 in 100,000 had mastectomy. In 2004-06 the rates were 57.9 and 50.8, respectively. The percentage of women with DCIS or breast cancer who were treated with BCT was lower in 2007-09 in all counties than in 2004-06. For 2007-09 the percentage of women with DCIS who were treated with BCT varied by county from 39% to 75%. For breast cancer the percentage varied from 33% to 67%. INTERPRETATION: The number and percentage of women with DCIS or breast cancer who were treated with BCT increased until 2005, then it fell, and the percentage varied between counties. The reasons for this need to be identified and followed up with regard to the recommendations from the Norwegian Breast Cancer Group.

Combined analysis of vascular invasion, grade, HER2 and Ki67 expression identifies early breast cancer patients with questionable benefit of systemic adjuvant therapy.

INTRODUCTION: Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome. MATERIAL AND METHODS: The current study included 346 unselected pT1pN0 patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995-1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cut-off 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death. RESULTS: Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p < 0.005, log rank). In multivariate analysis, only grade 1-2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS ≥ 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS ≥ 2 (p < 0.001), systemic relapse was detected in approximately 40%. CONCLUSIONS: This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy.

Recall mammography and psychological distress.

BACKGROUND: The aims of this study were (a) to identify psychological distress before and after being diagnosed with or without cancer in women recalled for further investigation because previous screening mammography indicated possible malignancy and (b) to document the willingness to attend and recommend mammography. Study participants included 526 recalled women (82% response) who completed a questionnaire before the recall mammogram and 4 weeks after receiving the result. Psychological distress was measured using the Hospital Anxiety and Depression Scale. RESULTS: Most subjects were diagnosed without cancer (87.6% false-positive rate). Recall after mammography among women with a false-positive mammogram was associated with transiently increased anxiety and a slight increase in depression. However, the level of anxiety was similar to and the level of depression was lower than in the general female Norwegian population. Women who received a cancer diagnosis had higher levels of anxiety and depression than the general female Norwegian population. Nearly all women (99%) were satisfied with their participation in the screening programme; 94% thought it was important, 98% would attend the next round of screening and 99% would recommend other women to attend. CONCLUDING STATEMENT: Recall after mammography was associated with transiently increased anxiety. Four weeks after screening, the level of anxiety was the same and depression was lower compared with the general female Norwegian population. The women were almost unanimously satisfied with their participation in the screening, would participate again and would recommend other women to participate.

Analysis of EpCAM positive cells isolated from sentinel lymph nodes of breast cancer patients identifies subpopulations of cells with distinct transcription profiles.

INTRODUCTION: The presence of tumor cells in the axillary lymph nodes is the most important prognostic factor in early stage breast cancer. However, the optimal method for sentinel lymph node (SLN) examination is still sought and currently many different protocols are employed. To examine two approaches for tumor cell detection we performed, in sequence, immunomagnetic enrichment and RT-PCR analysis on SLN samples from early stage breast cancer patients. This allowed us to compare findings based on the expression of cell surface proteins with those based on detection of intracellular transcripts. METHODS: Enrichment of EpCAM and Mucin 1 expressing cells from fresh SLN samples was achieved using magnetic beads coated with the appropriate antibodies. All resulting cell fractions were analyzed by RT-PCR using four chosen breast epithelial markers (hMAM, AGR2, SBEM, TFF1). Gene expression was further analyzed using RT-PCR arrays and markers for epithelial to mesenchymal transition (EMT). RESULTS: Both EpCAM and Mucin 1 enriched for the epithelial-marker expressing cells. However, EpCAM-IMS identified epithelial cells in 71 SLNs, whereas only 35 samples were positive with RT-PCR targeting breast epithelial transcripts. Further analysis of EpCAM positive but RT-PCR negative cell fractions showed that they had increased expression of MMPs, repressors of E-cadherin, SPARC and vimentin, all transcripts associated with the process of epithelial to mesenchymal transition. CONCLUSIONS: The EpCAM IMS-assay detected tumor cells with epithelial and mesenchymal-like characteristics, thus proving to be a more robust marker than pure epithelial derived biomarkers. This finding has clinical implications, as most methods for SLN analysis today rely on the detection of epithelial transcripts or proteins.

Hospital volume and prognosis among Norwegian breast cancer patients enrolled in adjuvant trials.

BACKGROUND: Several studies have reported an association between breast cancer unit volume and prognosis. We hypothesize that this may be due to inappropriate coping with the recommended guidelines for adjuvant therapy rather than improper breast cancer surgery provided at smaller units. METHODS: A cohort of 1131 patients with operable breast cancer (pT(1-2) and positive axillary lymph nodes, stage II) enrolled between 1984 and 1994 were analyzed. The women had participated in one of three prospective trials on adjuvant endocrine treatment and were enrolled from 50 centers in Norway. The hospitals were categorized into four groups according to the annual number of surgically treated breast cancer patients reported to the national discharge database in 1990. The hospitals were also stratified according to whether they are university or non-university hospitals. To assess the effect of unit size on patient outcome, local recurrence rates and overall survival were compared in women treated at units with different patient volumes. RESULTS: The median time from study enrolment to the end of the study was 10.5 years. Relapse-free survival and overall survival did not differ significantly between the hospital groups based on the surgical workload or between university and non-university hospitals. CONCLUSIONS: Patient volume or teaching status of a hospital did not have any impact on the prognosis of pre- or postmenopausal stage II breast cancer patients included in the adjuvant endocrine trials. Our data support the hypothesis that differences in survival related to patient volume at the treatment units may be explained by inappropriate adjuvant systemic treatment.