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Purpose: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC)., Methods: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed., Results: This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern., Conclusions: This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Improvements in the survival of patients with breast cancer, together with a better understanding of the pathology of the disease, have led to the emergence of bone health as a key aspect of patient management. Patients with breast cancer are typically at risk of skeletal complications throughout their disease course. The receptor activator of nuclear factor κ B ligand (RANKL) inhibitor denosumab and bisphosphonates (e.g. zoledronic acid) are approved in Europe for the prevention of skeletal-related events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) in adults with bone metastases secondary to solid tumours. These agents are also approved at lower doses for the treatment of patients with postmenopausal osteoporosis, a population largely overlapping with those in the early stages of breast cancer, and those with cancer treatment-induced bone loss, which is caused primarily by aromatase inhibitors. In this review, we consider the evidence supporting the use of therapeutic agents to protect bone health throughout the course of breast cancer. Timing of treatment initiation, dose and treatment duration may prove to be barriers to the optimization of the practical use of these agents in the management of patients with breast cancer. Furthermore, with longer survival times, patients may expect to receive long-term treatment with denosumab or bisphosphonates, therefore consideration must be given to safety. Thus, we aim to summarize the recommendations for the use of these agents in management of patients with breast cancer in Europe. We also discuss the recent evidence for their potential antineoplastic effects., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life. Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL)., Materials and Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors., Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 - 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences., Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In recent years, numerous new therapy options for patients with breast cancer have been developed in clinical studies, with some options already approved for routine treatment. As the speed at which innovations are introduced increases, the importance of conferences also increases, as conferences are where the data underpinning new therapies are usually presented for the first time. This review looks at publications of the ASCO (American Society of Clinical Oncology) and ESMO (European Society of Medical Oncology) conferences in 2017, summarizes them and evaluates them in the context of existing data. The focus is on new insights for neoadjuvant therapy and new treatment options in the metastatic setting, such as the use of CDK4/6 inhibitors or PARP inhibitors. The first results of treatments with checkpoint inhibitors are presented. With the patent expiry of trastuzumab, a number of study results for trastuzumab biosimilars have also been published. The digitization of patient care provides the first results on quality of life and prognosis of patients with advanced cancer. Digital communications between patients and physicians are being evaluated in several studies in Germany. As the discussion about patient-relevant endpoints for patients in the metastatic setting continues, overall survival rates from studies of big endocrine-based therapies are urgently needed. Preliminary analyses of small study cohorts offer initial insights. In the context of improving patient care, in the coming years, questions will center on which patients particularly benefit from certain therapies and which patients need particular protection from specific side effects. Questions about these predictors are raised in many scientific projects as attention increasingly focuses on this topic.

Purpose: Patient-reported outcomes (PROs) have been incorporated into clinical trials for many symptoms and medical conditions. A transition from paper-based capture of PROs to electronic PROs (ePROs) has recently started. This study reports on the feasibility of ePRO assessment in a prospective registry including molecular data for patients with advanced breast cancer., Methods: As part of the PRAEGNANT network, patients were invited by clinical trial staff, physicians, and nurses to complete three standardized Internet-based questionnaires (EQ 5D 5 L, CES-D and IPAQ). Feasibility was assessed by the staff members who assigned the user accounts by the patients. The completeness of the questionnaires was also assessed., Results: Fifteen of 17 patients who were asked agreed to participate to complete the PRO questionnaires (EQ-5D-5L and CES-D). However, the IPAQ (physical activity) questionnaire was only validly completed by 9 patients. Feasibility was ranked better by the physicians and dedicated clinical trial staff than by the nursing staff., Conclusions: Incorporating ePRO questionnaires into an advanced breast cancer registry is feasible, and no major hurdles were reported. Involving stakeholders from the start, the application is tailored to the capacities and abilities of both patients and clinical staff. The patients' compliance was better with some questionnaires, but others may present difficulties.

The St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer has been held regularly (every second year in the last six years) for more than 30 years. This year, the findings of the International St. Gallen Consensus Panel and their implications for clinical practice were again discussed by a German working group of leading breast cancer specialists. Five of the breast cancer specialists from Germany were also members of this year's St. Gallen panel. A comparison between the St. Gallen recommendations and the annually updated treatment guidelines of the Gynecologic Oncology Group (AGO 2017) and the S3-guideline agreed upon in 2017 is useful. The recommendations of the St. Gallen panel represent an international cross-section of opinions of experts from different countries and different disciplines, while the S3-guideline and AGO guidelines are evidence-based. The motto of this year's 15th St. Gallen Conference was "Escalating and De-Escalating". The rationale behind this concept was to promote more individualized treatment and thereby reduce overtreatment as well as undertreatment.

Purpose: The present study aims to analyze a cohort of advanced breast cancer patients in Germany to assess their interest in complementary and alternative medicine (CAM) and patient's use of most frequent CAM methods., Patients and Methods: Based on the PREGNANT real-time breast cancer registry which is a multicenter study in Germany, questionnaires of 580 patients with advanced breast cancer were evaluated. The implemented questionnaire for CAM asked for general interest in CAM and for patient's use of different CAM methods at present and in the past. The interest and application of CAM were analyzed for association with patients' characteristics such as tumor, patient, and therapy characteristics., Results: In total, 436 out of 580 (75%) patients claimed to be interested in CAM. Further, interest in CAM is significantly correlated with younger age and absence of metastasis at the time of diagnosis. Multivariate analysis confirmed the patient's age and distant disease status at the time of diagnosis as related to interest in CAM. A total of 56.4% of patients applied any CAM method in the past. Moreover, with increasing lines of therapies, the more frequent use of CAM was observed. Hereby, praying, vitamin supplements, and other food supplements were most frequently applied., Conclusion: Our data demonstrate high overall interest and frequent use of CAM in advanced breast cancer patients supporting a strong demand of breast cancer patients for complementary counseling and treatments additional to the established cancer therapies. It is indispensable to implement counseling and evidence-based complementary treatments into clinical routine of cancer centers and to adapt postgraduate medical education, respectively.

Purpose: The aim of this study is to provide an overview of the potential barriers to uptake of bone-targeted agents for the prevention of skeletal-related events (SREs) in patients with breast cancer and bone metastases., Methods: A top-line literature review was conducted to identify trends in and barriers to initiating bone-targeted therapy in patients with metastatic breast cancer., Results: The majority of patients with bone metastases that are secondary to breast cancer clearly benefit from treatment with a bone-targeted agent such as the RANK ligand inhibitor denosumab or the bisphosphonate zoledronic acid, because both delay the onset of SREs. Evidence suggests, however, that these agents are not being used in these patients as per European guideline recommendations., Conclusions: Adoption of a number of behavioral changes may help to overcome barriers to earlier initiation of treatment with bone-targeted agents in these patients. This includes raising awareness of the guidelines that are available for bone-targeted therapies, providing physician and patient education on the appropriate use of these agents, and highlighting to physicians the importance of early treatment and regular monitoring for adverse events. Earlier initiation of treatment should help to reduce the risk of SREs and thus lessen the burden that these debilitating skeletal complications place on patients and healthcare systems.

As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

Background: Bone is a frequent site of metastases in advanced cancer and is associated with significant skeletal morbidity. Current treatment options are aimed at preserving and improving functional independence and quality of life., Materials and Methods: A review of current literature focusing on diagnostic tools and treatment approaches of bone metastasis in advanced cancer was performed and conclusions were incorporated into diagnostic and treatment algorithms., Results: Radiologic imaging has added valuable tools for screening and diagnostics of bone metastasis. Clinical management of skeletal metastasis includes improved pain management, introduction of bone modifying agents and advancements in surgical and radiation therapy. We propose three algorithms enhancing the sensitivity of diagnostics and improving multidisciplinary management of vertebral and non-vertebral bone metastasis., Conclusion: Bone metastases are an expression of a systemic disease. Treatment options include highly specialized modalities yet need to be tailored to individual needs. Algorithms help standardize treatment procedures and can improve treatment outcome in a multidisciplinary setting., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients' perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors ('survivorship issues'), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success ('patient-reported outcome measures') and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany.

Bone complications or skeletal-related events (SREs), typically defined as radiation to bone, pathological fractures, surgery to bone and spinal cord compression, occur frequently in patients with bone metastases. As the survival of patients with advanced lung cancer improves, preventing SREs is becoming increasingly clinically relevant. The aim of this analysis was to assess the impact of SREs on health resource utilisation (HRU) in European lung cancer patients with bone metastasis. This multinational, observational study included patients who had at least one SRE in the 97 days prior to enrolment, a life expectancy of ≥6 months and an Eastern Cooperative Oncology Group performance status of 0-2. Data on HRU were retrospectively collected for up to 97 days prior to enrolment with a planned prospective follow-up for up to 18-21 months. The HRU measures included the number and length of inpatient hospitalisations and the number of outpatient visits and procedures. The investigators determined whether each HRU was attributable to a SRE. In total, 135 patients with lung cancer, enrolled at centres in Germany, Italy, Spain and the United Kingdom, contributed 214 SREs to this analysis. The median length [quartile (Q)1, Q3] of follow-up ranged from 1.5 (0.7, 3.3) to 5.6 (2.0, 8.2) months across the countries. Overall, 41% of the SREs required an inpatient stay, with a median (Q1, Q3) duration of 19.0 (6.0, 28.0) days. Spinal cord compression and surgery to bone were the SRE types most frequently requiring inpatient stays. Radiation to bone was associated with the largest number of outpatient visits and procedures. All the SREs resulting from bone metastases in patients with lung cancer contribute considerably to HRU and efforts to minimise the incidence of bone complications in these patients through appropriate treatments may help reduce this burden.

Purpose: Chemotherapy with anthracyclines, taxanes, or alkylating agents often causes cutaneous side effects. Nonspecific inhibition of the proliferative activity of keratinocytes has antidifferentiation effects that lead to defects in the barrier function and, thus, to dry, itchy, and irritable skin. These cutaneous symptoms reduce the quality of life of the patients considerably. Conditioning with topical application of niacinamide uses the cytoprotective and barrier stabilizing effect of vitamin B3., Patients and Methods: A multicenter randomized crossover study investigated the influence of the test preparation on the quality of life compared to standard care for 73 patients with breast cancer undergoing adjuvant or neoadjuvant cytostatic therapy. Primary target parameter was the Dermatology Life Quality Index with its respective subscales after 6 weeks of a twice-daily application of the respective preparations. Additionally, specific symptoms such as pruritus, dryness, and irritability have been assessed using visual analog scales., Results: Regarding the total score of the Dermatology Life Quality Index, no relevant differences could be observed. However, the results for the "symptoms and feelings" subscale show a significant advantage in favor of the test preparation. Significant superiority of the test preparation could also be observed in the secondary target parameters, the visual analog scales (P<0.05)., Conclusion: The results show for the first time a significant superiority of prophylactic application of niacinamide for maintaining quality of life while undergoing cytostatic treatment.

This study aimed to increase the understanding of health resource utilization (HRU) associated with skeletal-related events (SREs) occurring in patients with bone metastases secondary to advanced prostate cancer. A total of 120 patients from Germany, Italy, Spain and the United Kingdom were enrolled in this observational study. They had bone metastases secondary to prostate cancer and had experienced at least one SRE in the 97 days before giving informed consent. HRU data were collected retrospectively for 97 days before enrolment and prospectively for up to 18-21 months. HRU, including the number and duration of inpatient hospitalizations, number of outpatient and emergency department visits and procedures, was independently attributed by investigators to an SRE. Of the 222 SREs included in this analysis, 26% were associated with inpatient stays and the mean duration per SRE was 21.4 days (standard deviation (SD) 17.8 days). Overall, 174 SREs (78%) required an outpatient visit and the mean number of visits per SRE was 4.6 (SD 4.6). All SREs are associated with substantial HRU. Preventing SREs in patients with advanced prostate cancer and bone metastases may help to reduce the burden to both patients and European healthcare systems.

Patients with breast cancer and bone metastases often experience skeletal complications (skeletal-related events [SREs]: pathologic fracture, radiation to bone, surgery to bone or spinal cord compression). Prospective data on the health resource burden of SREs are needed for planning healthcare requirements and estimating the value of new treatments, but limited data are available. This prospective, observational study collected health resource utilization (HRU) data independently attributed to SREs by investigators. Eligible patients had bone metastases secondary to breast cancer, life expectancy ≥6 months, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and at least one SRE in the 97 days before enrollment. Data, collected retrospectively for 97 days before enrollment and prospectively for 18-21 months, included number and duration of inpatient stays, outpatient visits, emergency room visits and procedures. Altogether, 223 patients were enrolled from Germany, Italy, Spain and the UK. Of the 457 SREs, 118 (25.8%) were associated with inpatient stays. The mean duration of stay was 19.5 (standard deviation [SD] 19.2) days per SRE (based on 117 SREs). Surgery to bone and spinal cord compression were the SREs most likely to require inpatient stays (77.8% and 57.9% of SREs, respectively), while radiation to bone was the least likely (9.7%). Spinal cord compression required the longest inpatient stay per event (34.2 [SD 30.2] days) and radiation to bone the shortest (14.3 [SD 10.2] days). Overall, 342 SREs (74.8%) required an outpatient visit, with radiation to bone the most likely (85.7%), and surgery to bone the least likely (42.6%). Radiation to bone was also associated with the greatest number of outpatient visits per event (6.8 [SD 6.7] visits). All SREs were associated with substantial HRU therefore, preventing SREs in patients with breast cancer may reduce the burden imposed on healthcare systems.

Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), an intracellular protein kinase downstream of the phosphatidylinositol 3-kinase/AKT pathway involved in key components of tumorigenesis, including cell growth, proliferation, and angiogenesis. In the advanced cancer setting, based on favorable results from phase III trials, everolimus is indicated for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, and advanced hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma. Although it is generally well tolerated, with most adverse events of mild to moderate severity and manageable, everolimus exhibits a distinct adverse event profile that warrants guidance for proper diagnostic and medical management. This guidance is particularly important given the potential for widespread long-term use of everolimus. This review will focus on the most relevant toxicities associated with mTOR inhibitors and on their management. Practical treatment recommendations are presented for stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections. Provided these events are rapidly identified and treated, the vast majority should resolve with minimal effect on treatment outcomes and patients' quality of life., (Copyright © 2013 S. Karger AG, Basel.)

The surface receptor CUB domain-containing protein 1 (CDCP1) is highly expressed in several adenocarcinomas and speculated to participate in anchorage-independent cell survival and cell motility. Tyrosine kinase phosphorylation seems to be crucial for intracellular signaling of CDCP1. Lapatinib, a tyrosine kinase inhibitor (TKI), is approved for treatment of HER-2/neu overexpressing metastatic breast cancer and functions by preventing autophosphorylation following HER-2/neu receptor activation. This study aimed to investigate the effect of CDCP1 expression on anchorage-independent growth and cell motility of breast cancer cells. Moreover, studies were performed to examine if lapatinib provided any beneficial effect on HER-2/neu((+)/-)/CDCP1(+) breast cancer cell lines. In our studies, we affirmed that CDCP1 prevents cells from undergoing apoptosis when cultured in the absence of cell-substratum anchorage and that migratory and invasive properties of these cells were decreased when CDCP1 was down-regulated. However, only HER-2/neu(+), but not HER-2/neu((+)/-) cells showed decreased proliferation and invasion and an enhanced level of apoptosis towards loss of anchorage when treated with lapatinib. Therefore, we conclude that CDCP1 might be involved in regulating adhesion and motility of breast cancer cells but that lapatinib has no effect on tyrosine kinases regulating CDCP1. Nonetheless, other TKIs might offer therapeutic approaches for CDCP1-targeted breast cancer therapy and should be studied considering this aspect., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background/aim: The aim of the present study was to investigate the effects of conventional and dose-dense chemotherapy on serum levels of soluble adhesion molecules sICAM-1 and sVCAM-1 in node-positive patients with breast cancer., Patients and Methods: sICAM-1 and sVCAM-1 were measured in the blood serum of 147 patients with breast cancer and with 1 to 3 affected lymph nodes prior to and after conventional or dose-dense chemotherapy within a randomized phase III study (NOGGO trial)., Results: The increase in sICAM-1 (p<0.0001) and sVCAM-1 (p<0.001) levels after chemotherapy was statistically significant within the entire sample and the dose-dense study arm. sVCAM-1 levels were not altered by conventional chemotherapy, but were markedly and significantly increased after the dose-dense regimen. Higher sICAM-1 concentrations were found in postmenopausal patients, and the difference was significant before, but not after treatment. There was no significant correlation with other prognostic criteria., Conclusion: Both sVCAM-1 and sICAM-1 levels changed significantly after adjuvant chemotherapy, the effect being more marked under the dose-dense regimen. The possible prognostic relevance of adhesion molecule concentration and the effect of different modes of chemotherapy remains to be determined.

Background: A randomized phase II trial was conducted to determine if two non-platinum protocols are able to yield a similar efficacy and toxicity profile as compared to two platinum-based doublets in advanced non-small cell lung cancer (NSCLC)., Patients and Methods: A total of 61 patients were randomly assigned to a reference regimen of carboplatin and paclitaxel (repeated every 3 weeks) or to one of three experimental regimens: paclitaxel plus vinorelbine (repeated every 3 or 4 weeks) and carboplatin plus paclitaxel (repeated every 4 weeks)., Results: The objective remission rate for all the patients was 34.1%. The median progression-free survival for all the patients was 3 months. The median overall survival and one-year overall survival were 6 months and 21.5%, respectively. Toxicity was moderate and manageable. Response, survival and toxicity did not significantly differ between the four treatment groups., Conclusion: The efficacy and toxicity profile of platinum-free combinations is comparable to that of platinum-based doublets.

Background: Evidence suggests that cytokines (IL-6) and alteration of the hypothalamic-pituitary-adrenal (HPA) axis play a crucial role in the etiology of depression. Patients with cancer show elevated prevalence rates for depression. The objective of this cross-sectional study was to investigate the associations between these abnormalities and depression., Methods: Plasma concentrations of IL-6 and cortisol were measured in cancer patients with (N = 31) and without depression (N = 83). The relative diurnal variation of cortisol (cortisol VAR), expressed in percentage, was calculated., Results: There was a significant difference in median plasma concentration of IL-6 between the patients with depression and those without (18.7 vs 2.7 pg/mL; P < .001). Relative cortisol VAR was decreased in depressed patients as compared with patients without depression (11.72% vs 60.6%, P = .037). A positive correlation between the depressive symptoms and IL-6 concentration was found (r = 0.469, P < .001). Negative correlations were found between cortisol VAR versus depressive symptoms and cortisol VAR versus IL-6 (r = -0.6, P < .001 and r = -0.52, P < .001, respectively). IL-6 (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0-1.2; P = .006) and cortisol VAR (OR = 1.3; 95%CI = 1.0-1.4; P = .02) are independently associated with depression., Conclusions: Depression in cancer is associated with increased plasma IL-6 concentrations and dysfunction of the HPA axis.

Introduction: In sequence to our first survey in 2004 on antihormonal therapy with aromatase inhibitors (AIs), we conducted a second survey on the prescription practice in 2005., Material and Methods: We distributed the anonymous questionnaires amongst the participants of the 2005 congresses of the German Society of Senology and German Society of Haematology and Oncology., Results: The surveys were mostly completed by gynaecologists (46%) and medical oncologists (46%). According to the responses given, over 31,000 breast cancer patients were treated in these institutions in 2004, over 18,000 of whom received AIs. 37/30% of doctors prescribed AIs for national/private health insurance patients depending on the known risks of tamoxifen treatment (> 50% of cases). Whilst only 6/10% of doctors prescribed AIs for more than 50% of patients with either national/private health insurance in 2004, this figure reached 49% in 2005, independent of the type of medical insurance. Assuming unrestricted approval, 68/65% of doctors would treat over 50% of their patients with an AI., Conclusion: The rate of treatment with AIs has increased dramatically. The previous gold standard, tamoxifen, was by and large replaced by AIs in 2004/2005. We may assume that almost all receptor- positive breast cancer patients will receive an AI in the course of their adjuvant therapy in the very near future.

Background: The goal of the present study was to investigate the changes in concentration of the important lymph-angiogenesis factors vascular endothelium-derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy., Materials and Methods: The blood plasma of a total of 142 patients with breast carcinoma and with 1 to 3 affected lymph nodes was investigated, using the quantitative sandwich enzyme immunoassay technique, prior to and following chemotherapy, within the framework of a randomized phase III study: the patients received either conventional or dose-intensified chemotherapy., Results: In general, there was a significant reduction in VEGF levels after chemotherapy only in patients with large tumors (T3) (p = 0.043). There was also an almost significant reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p = 0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a positive hormone receptor status (p = 0.04) or in patients with a low expression of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on VEGF-D was determined only in patients who had a baseline level that was above the normal (conventionel treatment p = 0.005; dose-intensified treatment p = 0.004)., Conclusion: Both VEGF and VEGF-D levels changed after chemotherapy, depending on the patient and tumor characteristics. With respect to changes in the plasma levels of VEGF and VEGF-D, there were no significant differences between dose-intensified and conventional chemotherapy.

Introduction: The prescription practice of adjuvant therapy with aromatase inhibitors (AI) in Germany is not known, also considering that approval is still limited or awaited. We conducted a survey among breast specialists of the German Society of Senology., Method: A standardized questionnaire and the latest abstracts of the 3 trials were sent out to 1,223 members, responses were anonymized. All questions were to be answered with respect to the patients' national health insurance (NHS) or private health insurance (PHS) status., Results: Questionnaire were predominantly completed by gynecologists (82.4%). In all, >16,000 breast cancer patients had been treated in 2003. A total of 69.4% of physicians initiated adjuvant AI in up to 25% of NHS patients, 5.6% treated >50% of patients. However, 10.3% of physicians treated >50% of their PHS patients with an AI. Under the hypothesis of an unrestricted label for AI, 44.5% of physicians would treat >50% patients. The switch to an AI after 2-3 years of tamoxifen was chosen in 22% for NHS patients and in 36% of PHS patients. Continuing an AI after 5 years of tamoxifen was favored. in 26% of NHS and 35% of PHS patients., Conclusion: Tamoxifen as the previous gold standard is being replaced by AI; a dramatic change in treatment pattern is expected with less restricted approval.

Neutropenia is the most important dose-limiting toxicity of myelotoxic chemotherapy. Current guidelines recommend primary prophylactic use of granulocyte colony stimulating factor (G-CSF) with chemotherapy regimens associated with an incidence of febrile neutropenia (FN) of at least 40% and in patients at high risk of infections, such as the elderly. Using prophylactic G-CSF support, planned chemotherapy doses are administered on time more frequently. Pegfilgrastim is a rationally designed recombinant human G-CSF with a sustained duration of action. A once-per-cycle 6-mg fixed dose of pegfilgrastim reduced the duration of severe neutropenia and the incidence of FN as efficiently as daily filgrastim in standard or dose-dense chemotherapy regimens in young and elderly patients with breast cancer, non-small-cell lung cancer and lymphomas. The safety profile of onceper- cycle pegfilgrastim is comparable with that of daily filgrastim. In conclusion, a fixed-dose of pegfilgrastim given once per cycle is a suitable substitute for body weight-based daily dosing of G-CSF, an improvement which should be particularly beneficial for outpatients receiving myelotoxic chemotherapy.

Objectives: The HER-2/neu oncogene is overexpressed in many types of cancer and especially in 25% to 30% of breast cancers. Single reports mention HER-2/neu positivity in hematological malignancies like Hodgkins's disease and even diffuse large-cell lymphoma., Objective: To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma., Materials and Methods: Serum samples from 87 consecutive unselected patients with non-Hodgkin's lymphoma were retrospectively retrieved from a serum bank and tested for the shed antigen of HER-2/neu using the Oncogene Sciences ELISA assay (Cambridge, MA, USA). From those lymphoma patients, the paraffin-embedded lymph-node specimens of 25 cases with diffuse large-cell lymphoma were stained with the HER-2/neu DAKO HercepTest., Results: In 87 lymphoma patients, the serum level of HER-2/neu ranged from 3.6 to 244.1 ng/ml (median 8.0 ng/ml). Only 2 patients showed a marginal or increased HER-2/neu level with 15 ng/ml (which is the upper limit of normal) and 244.1 ng/ml, respectively. No patient with diffuse large-cell lymphoma showed HER-2/neu overexpression by immunhistochemistry of the lymph node. The paraffin block of the one patient with a very high HER-2/neu serum level was also stained for HER-2/neu overexpression. In this patient, suffering from a high-grade T-cell non-Hodgkin's lymphoma, no staining could be found., Conclusion: HER-2/neu is not overexpressed in non-Hodgkin's lymphoma and especially not in diffuse large-cell lymphoma, using a standardized immunochemistry technique with complementary serum testing. Thus, specific anti-HER-2/neu-targeted therapy should play no role in the treatment of non-Hodgkin's lymphoma.

Elevated levels of the extracellular domain of HER-2/neu in serum (sHER-2/neu) have been shown to be of prognostic importance. In this phase II study with weekly paclitaxel in metastatic breast cancer, we investigated the predictive quality of this serum oncoprotein by correlating the outcome of therapy to sHER-2/neu levels. Paclitaxel (90 mg/m2 weekly x6, q9w) was administered to 35 patients with complete outcome assessment and biochemical follow-up. sHER-2/neu was measured using standardized enzyme-linked immunoassays. We found that 62.9% (22/35) of the patients had elevated levels (> or = 15 ng/ml) of sHER-2/neu. The overall response rate (RR) to weekly paclitaxel was 40.0% (14/35). There was no difference in RR between sHER-2/neu-positive patients (40.9%) and sHER-2/neu-negative patients (38.5%; p = 0.4). The progression-free interval was longer for sHER-2/neu-negative patients (53.2 weeks) in comparison to sHER-2/neu-positive patients (31.2 weeks; p = 0.098). Responses were significantly more durable in sHER-2/neu-negative patients (65.2 weeks) than in the sHER-2/neu-positive subgroup (25.7 weeks; p = 0.042). Introducing hypothetical cut-offs into the sHER-2/neu-positive subset, we found that in patients with a sHER-2/neu level of greater than 22 ng/ml, the progression-free survival decreased significantly with increasing sHER-2/neu levels (p < or = 0.022). Considering the high impact of progression-free survival and duration of response as outcome parameters, the sHER-2/neu status is a predictive indicator for benefit from paclitaxel chemotherapy.

The clinical role of HER-2/neu, a 185 kD epithelial transmembranous protein, has evolved after the approval of the anti-HER-2/neu targeted monoclonal antibody trastuzumab (Herceptin) for the therapy of metastatic breast cancer. The extracellular domain of HER-2/neu undergoes proteolytic cleavage from the full-length protein by metalloproteases, and is shed into the blood as a circulating antigen. While HER-2/neu gene amplification and/or protein overexpression are detected in approximately 25% of primary breast cancers, serum HER-2/neu levels are elevated beyond the upper limit of normal in 50 to 60% of stage IV breast cancer patients. HER-2/neu in serum can be detected by enzyme immunoassays (manual and automated versions). It has been shown to have prognostic and predictive information in breast cancer patients. Monitoring for recurrence by serum HER-2/neu reaches a high sensitivity for HER-2/neu positive tumors. Longitudinal follow-up of patients during any kind of systemic therapy allows for monitoring of the therapeutic success. When utilized in these applications, serum HER-2/neu testing is complementary to HER-2/neu tissue results and to the determination of classical tumor markers such as CA 15-3, CA 27.29 and CEA, which are not targeted by specific forms of systemic therapy.

Purpose: The objective of this study was to evaluate the efficacy and tolerability of leuprorelin acetate in adjuvant treatment in comparison to standard chemotherapy with CMF in premenopausal, estrogen-receptor-positive or unknown, node-positive patients with early breast cancer., Patients and Methods: The patients were randomly assigned to receive either 2 years of hormone ablation with leuprorelin acetate 11.25 mg as a subcutaneous injection every three months or six courses of CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1 and 8, q 4 weeks). The primary study end-point was recurrence-free survival (RFS) after 2 years. Secondary end-points included overall survival, adverse events and hormonal suppression., Results: Between 1995 and 1999, a total of 589 patients with breast cancer were randomized to treatment with leuprorelin acetate or CMF. The data of 227 patients were available for this first interim analysis. One hundred and ten and 117 patients were assigned to leuprorelin acetate and chemotherapy, respectively. Both treatment arms were well balanced for baseline characteristics. So far, no difference between the groups has emerged with respect to recurrence-free or overall survivaL Suppression of serum estradiol levels and menstruation was less marked in the CMF-group compared to the leuprorelin arm. The most common adverse events were low-grade hot flushes, weight gain and increased sweating in the leuprorelin-treated patients and alopecia, nausea and vomiting in the CMF-group., Conclusion: According to these preliminary results, ovarian suppression with leuprorelin acetate was as effective as standard chemotherapy for premenopausal women with hormone-sensitive, node-positive early breast cancer.

Breast cancer remains a leading cause of cancer death in women despite widespread screening, in part because screening mammography has high rates of false-negative results and because many women decline to have routine mammograms. The development of sensitive and specific assays for breast tumor markers would improve detection and facilitate screening, diagnosis, therapeutic monitoring and surveillance for recurrence. Nuclear matrix proteins (NMPs) are promising candidates for tumor markers because they are involved in malignant transformation. Therefore, they may be useful for screening and early diagnosis of small tumors. Proteomic analysis was used to demonstrate that a 28.3 kD serum protein, designated NMP66, can distinguish malignant disease from benign conditions and normal controls. NMP66 is now being evaluated as a potential biomarker for early breast cancer detection in large-scale clinical trials.