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Introduction: The presence of axillary lymph node involvement is an important prognostic factor and has a major impact on treatment decisions in early breast cancer patients. This study aimed to determine the role of cortical thickness in axillary ultrasound (AUS) as an indicator of lymph node metastasis. Methods: 766 patients with primary breast cancer who received AUS during clinical work-up were selected for this retrospective study. Lymph nodes were defined as suspicious if they showed a cortical thickness of >3.0 mm at 11–15 MHz harmonic imaging ultrasound. Lymph node involvement was assessed by core needle biopsy (n = 150), sentinel node dissection or axillary dissection. Extensive axillary spread (EAS) was diagnosed if more than two lymph nodes showed metastatic disease in histology. Results: AUS for detecting all lymph node metastases had a sensitivity of 62.27%, a specificity of 93.15% and a negative predictive value of 81.74%. However, the resulting negative predictive value for transcapsular growth was 93.97%, and for EAS 97.52%. Conclusion: EAS – in contrast to non-palpable involvement of 1 or 2 lymph nodes – contributes relevantly to the individualization of breast cancer treatment. In combination with SNB, AUS using cortical thickness as the main distinctive parameter seems to be an easily available, robust tool of diagnosing extensive axillary metastases. If AUS proves negative, it helps to reduce the number of classic axillary dissections. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the leading cause of death from cancer in women and the most common cancer in the world [1]. To date, many patients with estrogen-receptor-positive (ER+) breast cancer are overtreated with chemotherapy when the rationale for adjuvant chemotherapy is based on clinicopathologic parameters. Different studies were able to demonstrate that a 21-gene expression assay (Oncotype DX® Genomic Health, Redwood City, CA) can predict the benefit from adjuvant chemotherapy in ER+ breast cancers [2, 3] and provide additional prognostic information independent of clinicopathological features [4].Results: Data from all patients with ER+ Her2neu- breast cancer undergoing Oncotype DX® testing between 2011 and 2014 at a tertiary referral center in Germany were analyzed. Oncotype DX® was performed in 69 cases, in 2 cases data were missing and in 3 cases Oncotype DX® could not be performed by the company. The results showed a low risk in 39 cases, an intermediate risk in 22 cases and a high risk in 3 cases. Based on Oncotype results, treatment recommendations were changed in 39 of 64 patients (61%). Before Oncotype DX® testing, chemotherapy was recommended in 67 patients, afterwards only in 25 patients. Data from 44 of 67 patients were matched to controls for stage, tumor grade, menopausal and hormone receptor status. Within a mean observation time of 19.7 months, cancer recurrence was observed in two patients.Conclusions: Oncotype DX® testing can be recommended for risk-tailored chemotherapy. Results should be validated in larger prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: Some reproductive factors are well-known general risk factors for breast cancer (BC). On the other hand, BC subtypes also have a high prognostic value. Correlations, however, that link these risk factors to the development of a particular one of the different BC subtypes are still poorly understood. The primary objective of our study was to assess the influence of different reproductive factors (duration of breastfeeding, parity, and age at first childbirth) on pathological BC subtypes. Secondarily, we correlated body mass index (BMI), age at primary diagnosis, and smoking behavior with tumor subclasses.Patients and Methods: We performed a retrospective chart review of 1082 patients with BC who had been treated for postmenopausal BC at the Heidelberg University Hospital during the period 2009-2014. For statistical analysis, different types of correlation analysis as well as a logistic regression model were used.Results: Relating to the primary objective, we found that patients with luminal-like BC had significantly fewer children than patients with triple-negative or HER2-positive subtype tumors (P = 0.027). Concerning the duration of breastfeeding, patients with a luminal A-like tumor had a significantly lower mean nursing period than patients with other subtypes (P = 0.012). Furthermore, patients who did breastfeed presented with a significantly lower number of hormone receptor-positive tumors (estrogen receptor-positive, P = 0.04; progesterone receptor-positive, P = 0.017) but the highest rate of HER2-overexpressing malignancies (P = 0.011). Moreover, late first childbirth was associated with the occurrence of luminal tumors (OR 0.952; P = 0.041). Regarding our secondary aim, higher BMI (P = 0.031) and higher age at primary diagnosis (P = 0.038) were both found to be significantly associated with luminal-like BC.Conclusion: The results suggest a correlation of the occurrence of luminal-like BC subtypes with low parity and short or no duration of breastfeeding. Prospective investigations are needed for further confirmation and to evaluate the molecular basis of our findings. [ABSTRACT FROM AUTHOR]

The article focuses on the importance of immunotherapy as possible treatment for breast cancer, witjh topics including the prevention of tumor progression, the patients management, and the effectiveness of chemotherapy to eliminate cancer cells.

Abstract: Triple negative breast cancer (TNBC) is a heterogeneous group of tumours accounting for approximately 10–20% of all breast carcinomas. To identify biologically distinct subgroups of TNBC and to assess their clinical properties we examined a series of 142 consecutive patients all of which had received adjuvant cytotoxic chemotherapy using a comprehensive panel of immunostains. Hierarchical unsupervised cluster analysis based on the expression of 13 markers permitted separation of four distinct groups (basal A, basal B, basoluminal, luminal) with the main distinguishing features being cytokeratin (Ck5/6, Ck14, Ck19), EGFR, p53, p16, and Ki-67 expression. Clusters differed with respect to patient age, modified Bloom and Richardson grading, the presence of tumour necrosis, growth pattern and survival, both in uni- and multivariate analysis. Basal (A or B) tumours showed a substantially better outcome compared with basoluminal and luminal tumours. Our data underline the heterogeneity of TNBC and characterise potentially relevant biological subtypes. [Copyright &y& Elsevier]

Aberrant DNA methylation constitutes a well-established epigenetic marker for breast cancer. Changes in methylation early in cancer development may be clinically relevant for cancer detection and prognosis-based therapeutic decisions. In the present study, a combination of methyl-CpG immunoprecipitation (MCIp) and human CpG island (CGI) arrays was applied to compare genome-wide DNA methylation profiles in 10 low-grade in situ and invasive breast cancers against 10 normal breast samples. In total, 214 CGIs were found to be hypermethylated in ≥6 of 10 tumors. Functional term enrichment analyses revealed an overrepresentation of homeobox genes and genes involved in transcription and regulation of transcription. Significant hypermethylation of 11 selected genes in tumor vs. normal tissue was validated in two independent sample sets (45 tumors and 11 controls, 43 tumors and 8 controls) using quantitative EpiTyper technology. In tumors, median methylation levels of BCAN, HOXD1, KCTD8, KLF11, NXPH1, POU4F1, SIM1, and TCF7L1 were ≥30% higher than in normal samples, representing potential biomarkers for tumor diagnosis. Using the 90th percentile of methylation levels in normal tissue as cutoff value, 62-92% of in situ samples (n=13), 72-97% of invasive samples from the first validation set (n=32), and 86-100% of invasive samples from the second validation set (n=43) were classified as hypermethylated. Hypermethylation of KLFll and SIM1 might also be associated with increased risk of developing metastases. In summary, early methylation changes are frequent in the low-grade pathway of breast cancer and may be useful in the development of differential diagnostic and possibly also prognostic markers. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: In breast cancer patients, intraoperative bone marrow puncture (BMP) with positive detection of disseminated tumor cells has been reported to predict unfavorable clinical outcome due to increased risk of recurrence. In this study, we prospectively assessed BMP-associated untoward side-effects. Methods: Fifty-eight consecutive breast cancer patients were prospectively explored after intraoperative BMP for postoperative pain (visual analogue scale, VAS) and complications in terms of infection, hematoma, and sensibility disorder. Furthermore, the impact of BMP on hospital stay duration was analyzed in 254 patients. Results: In all subgroups analyzed, during five postoperative days patients complained about minor pain only at the site of BMP (VAS < 1) while the corresponding pain scores were significantly higher for the area of the operated breast. Post-BMP iliac crest hematomas were encountered in 13 out of 58 patients (22.4%) who were significantly older (p = 0.04), less frequently smokers (p = 0.02), and presented with higher body mass index (p = 0.01) than controls. Within the area of BMP no signs of infection or sensibility disorders were observed. Comparison of patients with and without BMP did not show any significant difference in postoperative hospital stay duration. Conclusion: Referring to the potential clinical benefit of intraoperative BMP its prospectively assessed adverse side-effects appear relatively mild and thus acceptable. [Copyright &y& Elsevier]

Abstract: This prospective cohort study was carried out to develop a German version of the Breast Cancer Treatment Outcome Scale (BCTOS) and to examine the relations of aesthetic and functional outcome after breast conserving surgery with quality of life (QoL). The study included 189 patients with one-sided, early stage breast cancer. A factor analysis indicated three internally consistent scales of the German BCTOS: Aesthetic Status, Functional Status and Breast Sensitivity Status. QoL was measured by the EORTC Quality of Life Questionnaire C30-BR23 (EORTC). All BCTOS scales were correlated with scales of the EORTC. Correlation magnitudes ranged from 0.24 to 0.67 (p < 0.001). A multiple regression analyses confirmed these results. The analysis of relevant covariates demonstrated that younger patients revealed poorer status on all BCTOS scales. Aesthetic and functional outcome seems to be closely related to quality of Life. The German BCTOS demonstrated to be a useful instrument. [Copyright &y& Elsevier]

Abstract: Biological changes in breast cancers during tumor progression can affect therapeutic parameters, such as hormone receptors. We studied a series of primary tumors and the matching recurrent lesions to analyze the frequency of this phenomenon and the impact on disease-free interval. The expression of ER, PgR, c-erbB2, CD44v6, and p53 in the primary and the locoregional tumor was analyzed in 70 patients with recurrent breast cancer. Antigen expression correlated well between the primary and the matching recurrent tumor for all antigens under study. However, hormone receptor expression was lost in more than 50% of the cases, without significant impact on the disease-free survival interval. The disease-free interval was significantly longer for PgR-positive primary tumors, but did not depend on the ER status. The expression or changes of c-erbB2, CD44v6, and p53 were not related to the recurrence-free time intervals. Therefore, for treatment, it seems important to consider a possible loss of hormone receptors during tumor progression. [Copyright &y& Elsevier]

Background: Breast cancer represents the most common malignant disease in women worldwide. As currently systematic palliative treatment only has a limited effect on survival rates, the concept of health-related quality of life (HRQoL) is gaining more and more importance in the therapy setting of metastatic breast cancer. One of the major patient-reported outcomes (PROs) for measuring HRQoL in patients with breast cancer is provided by the European Organization for Research and Treatment of Cancer (EORTC). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. Facing the possibilities associated with evolving digitalization in medicine, validation of electronic versions of well-established PRO is essential in order to contribute to comprehensive and holistic oncological care and to ensure high quality in cancer research.Objective: The aim of this study was to analyze the reliability of a tablet-based measuring application for EORTC QLQ-C30 in German language in patients with adjuvant and (curative) metastatic breast cancer.Methods: Paper- and tablet-based questionnaires were completed by a total of 106 female patients with adjuvant and metastatic breast cancer recruited as part of the e-PROCOM study. All patients were required to complete the electronic- (e-PRO) and paper-based versions of the HRQoL EORTC QLQ-C30 questionnaire. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability [Wilcoxon test] and test of internal consistency [Spearman rho and agreement rates for single items, Pearson correlation and Kendall tau for each scale]) were analyzed.Results: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patient's response behavior between paper- and electronic-based questionnaires. Regarding the test of parallel forms reliability, no significant differences were found in 27 of 30 single items and in 14 of 15 scales, whereas a statistically significant correlation in the test of consistency was found in all 30 single items and all 15 scales.Conclusions: The evaluated e-PRO version of the EORTC QLQ-C30 is reliable for patients with both adjuvant and metastatic breast cancer, showing a high correlation in almost all questions (and in many scales). Thus, we conclude that the validated paper-based PRO assessment and the e-PRO tool are equally valid. However, the reliability should also be analyzed in other prospective trials to ensure that usability is reliable in all patient groups.Trial Registration: ClinicalTrials.gov NCT03132506; https://clinicaltrials.gov/ct2/show/NCT03132506 (Archived by WebCite at http://www.webcitation.org/6tRcgQuou). [ABSTRACT FROM AUTHOR]

Considering the diverse functions of B cells, responses to tumor-associated antigens (TAA) have been thought to be the main source of B cell-mediated antitumor immunity. Polymorphic epithelial mucin (MUC1) is considered one of the most specific TAA in patients with breast cancer. The present study aims to dissect the level and subclasses of naturally occurring anti-MUC1 antibodies in regard to tumor biologic parameters, clinical characteristics and overall survival. In 288 primary, non-metastatic breast cancer patients, pretreatment serum levels of anti-MUC1 immunoglobulin G (IgG) and its subclasses G1–4 as well as immunoglobulin M (IgM) were analyzed via ELISA. With respect to overall survival (Kaplan–Meier analysis), tumor biologic parameters as hormone receptor status, human epidermal growth factor receptor 2 (Her2), Ki-67 expression and tumor grading have been correlated as well as clinical characteristics as nodal involvement, tumor stage and patients' age at the time of diagnosis. Median follow-up time was 148 mo (IQR: 73.1–158.5 mo). A significant increase in IgG antibody titers was correlated highly significantly with an improved overall survival of patients. In multivariate analysis, total IgG proved to be an independent prognostic marker for overall survival (p= 0.002). IgG subclass analysis did not reveal any correlation of IgG1, IgG3 and IgG4 levels with overall survival, while increased immunoglobulin G2 (IgG2) values, although statistically not significant, tended to correlate with prolonged patient survival. MUC1-specific IgM antibodies were shown not to be predictive of overall survival. Altogether, humoral immune responses appear to play a crucial part in the tumor immunity of breast cancer patients. The present data confirms the positive impact of tumor-specific IgG on prolonged overall survival in breast cancer patients. MUC1-antibody testing might be a useful tool to identify high-risk patients who may need adjuvant therapy and potentially might benefit from MUC1-directed immunotherapy. [ABSTRACT FROM PUBLISHER]

Triple-negative breast cancer (TNBC) is a group of very aggressive breast tumours, characterised by lack of expression of oestrogen receptor (ER), progesterone receptor (PR) and erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2). Nevertheless, TNBCs show different clinical characteristics and are very diverse regarding prognostic outcome. So far, only a few prognostic markers for TNBC have been reported that could be helpful for therapeutic stratification. Here we have analysed the expression of S100P and HYAL2 using immunohistochemistry (IHC) in a TNBC cohort of 98 patients with a follow-up for recurrence and death. TNBC patients with high expression of both proteins showed significantly shorter progression-free survival (PFS) (mean PFS = 35.9 months, P = 0.001) compared to TNBC patients with high expression levels of only one of the proteins (mean PFS = 69.4 months) and to TNBC patients with low expression of both proteins (mean PFS = 83.3 months). Moreover, multivariate Cox-regression model showed the combined expression of S100P and HYAL2 as independent prognostic factor for PFS ( P = 0.001). The expression of S100P and HYAL2 indicated similar prognostic effect to the overall survival (OS) of TNBC patients. In addition, high expression levels of both S100P and HYAL2 showed significant association with different clinicopathological characteristics, such as more recurrence events ( P = 0.004), and higher occurrence of metastasis ( P = 0.002). Our study proposes S100P and HYAL2 as potential prognostic markers for TNBC. [ABSTRACT FROM AUTHOR]