Epithelial­mesenchymal transition was identified as a potential marker for breast cancer aggressiveness using reverse transcription­quantitative polymerase chain reaction.

The primary cause of breast cancer­associated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT). As a different set of genes is upregulated during EMT, such genes may serve as marker genes for the detection of CTCs based on reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Therefore, EMT­ and breast cancer­related genes were selected as RT­qPCR markers. These genes were tested for performance in a model system of blood samples from healthy donors, to which a number of various breast cancer cell lines were added. The genes with optimal performance were subsequently used in RT­qPCR with 35 breast cancer patient samples. The genes which showed the highest and most consistent increase in gene expression with the increase in the number of cancer cell line cells added were CK19, Snail, FoxC2 and Twist. Following RT­qPCR for all patient samples, two subgroups were arranged: One group in which all genes were downregulated and the second group with at least one gene indicated an upregulation of gene expression. Comparisons were made between the tumour characteristics from these two groups. Results suggested that carcinomas of the first group exhibited a less aggressive tumor biology compared with those in the second group. The present study indicated a novel RT­qPCR based test for tumor malignancy.

LKB1 pro-oncogenic activity triggers cell survival in circulating tumor cells.

During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the epithelial-to-mesenchymal transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress. The aim of this study was to assess LKB1 expression in epithelial-negative CTCs isolated from patients with metastatic breast cancer and to characterize its possible association with EMT and stemness features. Transcriptome analysis of EpCAM-negative CTCs indicated that over 25% of patients showed enhanced LKB1 levels, while almost 20% of patients showed enhanced levels of an EMT transcription factor known as ZEB1. Transcriptome and immunofluorescence analyses showed that patients with enhanced LKB1 were correspondingly ZEB1 negative, suggesting complementary activity for the two proteins. Only ZEB1 was significantly associated with cancer stem cell (CSC) markers. Neither LKB1 nor ZEB1 upregulation showed a correlation with clinical outcome, while enhanced levels of stemness-associated CD44 correlated with a lower progression-free and overall survival. Ex vivo models showed that MDA-MB-231, a mesenchymal tumor cell line, grew in suspension only if LKB1 was upregulated, but the MCF-7 epithelial cell line lost its ability to generate spheroids and colonies when LKB1 was inhibited, supporting the idea that LKB1 might be necessary for CTCs to overcome the absence of the extracellular matrix during the early phases of intravasation. If these preliminary results are confirmed, LKB1 will become a novel therapeutic target for eradicating metastasis-initiating CTCs from patients with primary breast cancer.

Preference of elderly patients' to oral or intravenous chemotherapy in heavily pre-treated recurrent ovarian cancer: final results of a prospective multicenter trial.

BACKGROUND: Palliative systemic treatment in elderly gynaecological cancer patients remains a major challenge. In recurrent ovarian cancer (ROC), treosulfan an active alkylating drug showed similar cytotoxicity whether as oral (p.o.) or intravenous (i.v.) application. The aim of this innovative trial was to evaluate the preference of elderly patients (≥65 years) for p.o. or i.v. chemotherapy focusing compliance, outcome, toxicities, and geriatric aspects as secondary endpoints. METHODS: Patients with ROC had the free choice between treosulfan i.v. (7000 mg/m2 d1, q29d) or p.o. (600 mg/m2 daily d1-28, q57d). Only indecisive participants were randomized. RESULTS: Overall 123 patients with 2nd to 5th recurrence were registered and 119 received at least one cycle of chemotherapy. 85.7% preferred treosulfan i.v. and 14.3% oral, where only three patients were randomized. Main reasons for i.v. preference associated with individual expectations of lower rate of gastrointestinal disorders, higher activity and tolerability of treatment. Median of applied chemotherapies was three (range 1-12 cycles), with most common grade 3/4 toxicities thrombopenia (18.7%), leukopenia (15.7%), ascites (7.6%), bowel obstruction (6.7%), and abdominal pain (4.2%). Median time until progression/overall survival was 5.2/7.8 months (i.v.), and 5.6/10.4 months (p.o.), respectively, without significant differences in efficacy. CONCLUSIONS: Elderly patients with recurrent ovarian cancer asked and demonstrated active participation in the decision-making process of their oncological treatment and favoured predominantly the i.v. application. Treosulfan was generally well-tolerated despite comorbidities and heavy pre-treatment. Our study demonstrates that patients' preference did not influence prognosis negatively and remains important in gynaecologic oncology decision practice. EUDRACT NR: 2004-000719-25; NCT 00170690.

Comparison of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients.

PURPOSE: The detection of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients is an independent prognostic factor. In recent years, the focus of research was on finding methods for the detection of circulating tumor cells (CTC) in peripheral blood (PB). In this study, we investigated the presence of DTC-BM and CTC by simultaneous examinations in 202 patients at different stages of the disease. METHODS: Immunocytochemical examination of DTC-BM (10-20 ml of BM) with the anti-cytokeratin (CK) antibody A45B/B3 followed a standardized protocol. Analysis of PB (7.5 ml) for the presence of CTC was performed with the CellSearch Analyzer system (Veridex, Raritan, NJ, USA). RESULTS: Overall, DTC-BM were detected in 57/202 (28.2 %, 1->1,000 DTC) and CTC in 41/202 (20.3 %, 1-411 CTC) patients. Congruence of findings was 71.3 % (144/202, p = .002). In 147 pts with primary diagnosis, congruence of results was 69.4 % (102/147). There was no significant correlation between DTC or CTC and the established pathological factors. After a median follow-up time of 34 months (0-82), presence of CTC was borderline significant for tumor-associated death (p = .060). For 41 patients at recurrence-free follow-up, congruence of results was 75.6 % (31/41, p = .018). In this group, there was a patient with both the highest DTC (>1,000) and CTC (411) count, and she presented with distant metastases 3 months later and had died 5 months after that. Of 14 patients with metastatic disease, 9 showed both DTC and CTC (overall congruence 78.6 %, p = .176). CONCLUSION: There was significant congruence between DTC and CTC, which even increased in patients at follow-up and in those with metastases. Repeated CTC examinations could be a valuable tool for monitoring patients or the effectiveness of therapies.

Assessment of existing roadside swales with engineered filter soil: I. Characterization and lifetime expectancy.

Roadside infiltration swales with well-defined soil mixtures (filter soil) for the enhancement of both infiltration and treatment of stormwater runoff from roads and parking areas have been common practice in Germany for approximately two decades. Although the systems have proven hydraulically effective, their treatment efficiency and thus lifetime expectancies are not sufficiently documented. The lack of documentation restricts the implementation of new such systems in Germany as well as other countries. This study provides an assessment of eight roadside infiltration swales with filter soil from different locations in Germany that have been operational for 6 to16 yr. The swales were assessed with respect to visual appearance, infiltration rate, soil pH, and soil texture, as well as soil concentration of organic matter, heavy metals (Cd, Cr, Cu, Pb, Zn), and phosphorus. Visually, the swales appeared highly variable with respect to soil color and textural layering as well as composition of plants and soil-dwelling organisms. Three swales still comply with the German design criteria for infiltration rate (10 m/s), while the remaining swales have lower, yet acceptable, infiltration rates around 10 m/s. Six of the eight studied soils have heavy metal concentrations exceeding the limit value for unpolluted soil. Provided that the systems are able to continuously retain existing and incoming pollutants, our analysis indicates that the soils can remain operational for another 13 to 136 yr if the German limit values for unrestricted usage in open construction works are applied. However, no official guidelines exist for acceptable soil quality in existing infiltration facilities.

Final results of an international retrospective observational study in patients with advanced breast cancer treated with oral vinorelbine-based chemotherapy.

BACKGROUND: Full oral chemotherapy (CT) is an active and convenient therapeutic option for patients with advanced breast cancer (ABC). In this retrospective analysis, we reviewed the characteristics and the outcome of patients treated by oral vinorelbine either as a single-agent or in combination with capecitabine as first- or second-line CT in the metastatic setting. PATIENTS AND METHODS: We analysed 216 patients with ABC who started treatment with a full oral CT at 13 centers and seven countries between 2006 and 2008. To be eligible, patients must have received either as a first-(56%) or second-line (44%) therapy oral vinorelbine as a single-agent (54%) or in combination with capecitabine (46%). RESULTS: Main patients' characteristics in the full population (n=216): median age (range): 61 (32-87) years; categories of age: <50 years: 18%, 50-65 years: 44%, ≥ 65 years: 38%; hormone receptor-positive: 63%; ≥ 2 metastatic sites: 58%; visceral metastases: 49%; prior CT: 86%; prior CT for ABC: 44%; prior anthracycline treatment: 69%; prior taxane treatment: 43%, prior anthracycline plus taxane: 38%; prior endocrine therapy: 63%. Median number of cycles: 6 (range=1-54); 48% of patients received more than 6 cycles. G3/4 toxicities: neutropenia 8%, anaemia 2%, thrombocytopenia 1%, febrile neutropenia/neutropenic infection 2%, nausea 6%, vomiting 4%, diarrhea 6%, fatigue 6%, hand-foot syndrome 14% (combination with capecitabine), neuropathy 1%, alopecia (grade 2) 1%. EFFICACY: disease control was achieved in 77% of patients [95% confidence interval=71-83%], 74% as single-agent, 81% in combination, 82% in first-line, 71% in second-line. Median progression-free survival was 9.7 months [95% confidence interval=8.2-12.6 months] in first-line and 6.6 months [95% confidence interval=5.5-8.5 months] in second-line therapy. Caregivers described these oral regimens as convenient (81%), well-tolerated (84%) and with a good compliance by patients (76%). CONCLUSION: These data from everyday practice confirm, as shown in different clinical trials, that oral vinorelbine is an active and well-tolerated CT for ABC, either as a first- or second-line in patients pre-treated with anthracyclines or taxanes. The convenience of its oral administration in association with its good tolerance profile, allows for continuation of treatment until disease progression without a pre-planned maximum of cycles.

Health-related quality of life during sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: a multicenter phase ii study of the North Eastern German Society of Gynecological Oncology.

AIM: We describe the impact of a sequential dose-dense schedule of carboplatin and paclitaxel on the quality of life (QoL) of patients with ovarian cancer. PATIENTS AND METHODS: In this multicenter phase II trial, four cycles of carboplatin followed by 12 cycles of weekly paclitaxel were applied after cytoreductive surgery. QoL was assessed using the QoL questionnaires EORTC QLQ-C30 and QLQ-OV28 before chemotherapy (baseline), after four cycles of carboplatin, at the end of treatment (EOT), and after 6, 12, and 24 months. RESULTS: Out of 104 eligible patients 87 (84%) participated in at least one QoL assessment. At baseline, all QLQ-C30 scales and symptoms were significantly worse than age-adjusted values for the general population. Subsequently QoL improved in general. During chemotherapy with paclitaxel, most functioning scales and symptoms worsened slightly (not significantly). However, peripheral neuropathy and chemotherapy-related side-effects increased to clinically important levels. At the end of treatment, most QoL scores were similar to those of the general population, but physical functioning and fatigue were worse. Sexual functioning and peripheral neuropathy remained problematic. CONCLUSION: QoL was affected mainly by the weekly paclitaxel schedule, but effects were in most cases only temporary. A dose-dense regimen using a sequential protocol may be favourable in terms of QoL.

A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis.

BACKGROUND: Treosulfan, an alkylating agent, has demonstrated activity in recurrent ovarian carcinoma. It is equieffective as oral (p.o.) and intravenous (i.v.) formulation. To explore the preference and compliance of elderly patients regarding p.o. or i.v. treosulfan for the treatment of relapsed ovarian carcinoma, women aged 65 years or older were included in this prospective multicenter study. Since elderly patients usually have several concomitant diseases and experience more treatment toxicity, an interim safety analysis was planned and performed after 25 patients finished therapy to assess the tolerability of the treatment regimens. METHODS: Patients had a free choice of treosulfan i.v. (7,000 mg/m(2) day 1 of a 28-day cycle) or p.o. (600 mg/m(2) day 1-28 of a 56-day cycle) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). Indecisive patients were randomized. Toxicity was evaluated according to the NCI-CTC version 2.0. RESULTS: Twenty-five of 51 recruited patients completed therapy at the time of the planned interim analysis (median age, 75 years; range, 70-82). Median ECOG was 1, and median number of prior chemotherapy regimens was 2. A median number of 4 cycles (range, 1-12) were administered per patient. Anemia was the most common hematological toxicity (88 % of patients). Most frequent non-hematological toxicities were nausea (76 %), constipation (68 %), and fatigue (64 %). CONCLUSION: Treatment was generally well tolerated despite the fact that most patients suffered from multiple comorbidities and were heavily pretreated. There were no unexpected hematological or non-hematological toxicities. Based on this safety analysis, the next step of study recruitment was continued.

Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study.

PURPOSE: Observational studies suggested that luteinizing hormone-releasing hormone agonists (LHRHa) might prevent premature ovarian failure resulting from adjuvant chemotherapy in premenopausal patients. We aimed to test the efficacy of ovarian function preservation with the LHRHa goserelin in patients with breast cancer. PATIENTS AND METHODS: In a prospective, randomized, open-label, controlled multicenter study, 60 patients younger than age 46 years with hormone-insensitive breast cancer were allocated to receive anthracycline/cyclophosphamide (with or without taxane) -based neoadjuvant chemotherapy with or without goserelin. The first goserelin injection was administered at least 2 weeks before the first chemotherapy cycle, continuing at 3.6 mg subcutaneously every 4 weeks until the end of the last cycle. The primary objective was the reappearance of normal ovarian function, defined as two consecutive menstrual periods within 21 to 35 days at 6 months after end of chemotherapy. RESULTS: Fifty-three patients (88.3%) experienced temporary amenorrhea (93.3% with v 83.3% without goserelin). No significant difference was observed regarding the reappearance of menstruation at 6 months after chemotherapy (70.0% with v 56.7% without goserelin; difference of 13.3%; 95% CI, -10.85 to 37.45; P = .284). All but one evaluable patient reported regular menses at 2 years after chemotherapy. Time to restoration of menstruation was 6.8 months (95% CI, 5.2 to 8.4) with goserelin and 6.1 months (95% CI, 5.3 to 6.8) without goserelin (P = .304). Chemotherapy resulted in a decreased ovarian reserve measured by inhibin B and anti-Müllerian hormone during follow-up, supporting the other findings. CONCLUSION: Premenopausal patients with breast cancer receiving goserelin simultaneously with modern neoadjuvant chemotherapy did not experience statistically significantly less amenorrhea 6 months after end of chemotherapy compared with those receiving chemotherapy alone.

Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse--a European pooled analysis.

BACKGROUND: The prognostic significance of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients at the time of primary diagnosis has been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTCs after adjuvant therapy increases the risk of subsequent relapse and death. PATIENTS AND METHODS: Individual patient data from 676 women with primary diagnosis of early breast cancer stages I-III from 3 follow-up studies were pooled. During clinical follow-up, patients underwent BM aspiration (BMA) to determine the presence of DTC. Tumor cells were detected by the standardized immunoassays. Univariate and multivariable proportional hazards models were estimated to assess the prognostic significance of DTC for disease-free survival (DFS) and overall survival (OS). RESULTS: Patients were followed for a median of 89 months. BMA was performed at median 37 months after diagnosis of breast cancer. At follow-up BMA, 15.5% of patients had DTCs. The presence of DTC was an independent indicator of poor prognosis for DFS, distant DFS (DDFS), cancer-specific survival, and OS during the first 5 years following cancer diagnosis (log-rank test P < 0.001 values for all investigated endpoints). CONCLUSION: Among breast cancer patients, persistent DTCs during follow-up significantly predicted the increased risk for subsequent relapse and death. Analysis of DTC might serve as a clinically useful monitoring tool and should be tested as an indicator for secondary adjuvant treatment intervention within clinical trials.

Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group.

PURPOSE: Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with platinum-resistant recurrent ovarian cancer. We conducted a randomized phase II trial (TOWER [Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer]) to better define the ratio between benefits and risks with either treatment approach. PATIENTS AND METHODS: Patients were randomly assigned to two independent two-stage protocols of Tw (4 mg/m(2)/wk administered on days 1, 8, and 15) or Tc (1.25 mg/m(2)/d on days 1 to 5). We evaluated risk ratios (RRs) for the primary end point of clinical benefit (complete response, partial response, and stable disease), the duration of progression-free survival (PFS) and overall survival (OS), associated hazard ratios (HRs), and RRs of toxicity with 95% CIs. RESULTS: In total, 194 patients were randomly assigned at 54 centers to Tw (n = 97) or Tc (n = 97). Clinical benefit was observed in 36 of 76 (47%; 95% CI, 36% to 59%) Tw and 46 of 80 (58%; 95% CI, 46% to 68%) Tc patients (RR, 1.21; 95% CI, 0.90 to 1.64; P = .205). Patients in the Tw group had a slightly shorter PFS (HR, 1.29; 95% CI, 0.96 to 1.76) but similar OS (HR, 1.04; 95% CI, 0.74 to 1.45) compared with Tc. Tw was associated with significantly lower risks of anemia (RR, 0.35; 95% CI, 0.16 to 0.79), neutropenia (RR, 0.38; 95% CI, 0.23 to 0.65), and thrombocytopenia (RR, 0.23; 95% CI, 0.09 to 0.57). CONCLUSION: With regard to effectiveness in terms of response and PFS, Tc remains the standard of care in patients with platinum-resistant recurrent ovarian cancer. However, comparable OS rates and a favorable toxicity profile make Tw another viable treatment option in this setting.

Effect of zoledronate on persisting isolated tumour cells in patients with early breast cancer.

BACKGROUND: There is strong evidence for the isolated tumour cells (ITCs) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up. The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC. PATIENTS AND METHODS: A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up. Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy. In a matched-pair analysis, these patients were compared to 141 patients who did not receive additional zoledronate treatment. The bone marrow was re-examined after a median of 7.9 months (SD 0.89) and 11.5 months (SD 12.41; p=0.11), respectively. Patients were followed-up prospectively for a median of 39 months after the first aspiration. RESULTS: While ITCs were detected in all 172 patients at the time of first bone marrow aspiration, ITCs were detected in four patients (13%) following 6 months of zoledronate therapy in contrast to 38 patients (27%) of the control group (p=0.099). The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group (p=0.02 vs. p=0.14). Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival (p=0.05). CONCLUSION: These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state.

Prevalence of CA 27.29 in primary breast cancer patients before the start of systemic treatment.

BACKGROUND: Several trials show that tumor markers at primary diagnosis of cancer have prognostic relevance and can predict dissemination of the disease. While MUC-1 markers are frequently used to monitor treatment efficacy in metastatic breast cancer, their role at primary diagnosis or during follow-up remains unclear. This translational research project within the SUCCESS trial evaluates the role of the tumor marker CA 27.29 before and after adjuvant chemotherapy, as well as after two and then five years in patients with early breast cancer. PATIENTS AND METHODS: The SUCCESS trial compared FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) and two vs. five years of zoledronate treatment in node-positive and high-risk node-negative patients with primary breast cancer. CA 27.29 was measured before chemotherapy in 2669 patients with the reagent ST AIA-PACK CA 27.29 for AIA-600II-Analyzer (Tosoh Bioscience, Belgium). Results of CA 27.29 above 31 U/ml were regarded as positive. RESULTS: 7.6% of patients had elevated marker levels after the completion of primary surgical treatment but before initiation of chemotherapy (n=202, mean 19, range 3-410 U/ml). No correlation between nodal status (p=0.55), grading (p=0.85), hormonal status (p=0.21), HER2/neu status on the primary tumor (p=0.58) and CA 27.29 was shown. However, larger tumor size (p=0.02), lobular histology (p<0.0001), older age (p<0.001) and postmenopausal hormone status before the start of treatment (p=0.006) were significantly associated with higher CA 27.29 levels. CONCLUSION: These data indicate a close relationship between CA 27.29 and tumor mass persisting even several weeks after surgery, but also identify potential confounding factors that should be considered in interpreting tumor marker results. Further follow-up of the SUCCESS trial will clarify whether CA 27.29 measured after surgery but before the start of systemic treatment is prognostically relevant and whether it is a useful marker for treatment monitoring in the adjuvant setting.

Quality of life, anxiety, and oncological factors: a follow-up study of breast cancer patients.

BACKGROUND: The number of long-term survivors of breast cancer has increased over recent decades because of many treatment advances. Thus, long-term quality of life (QoL) and factors affecting it are of growing research interest. OBJECTIVE: The authors investigated longitudinal changes in QoL and anxiety in breast cancer patients and differences in QoL and anxiety in various oncological subgroups. METHOD: A group of 236 women with a primary diagnosis of breast cancer or carcinoma in-situ completed questionnaires after surgical treatment, 6 months, and 12 months post-surgery. RESULTS: QoL scores of breast cancer patients improved over time, but impairments in terms of anxiety, body image, and sexual functioning were still observed. Younger patients were more likely to be distressed by cancer diagnosis and treatment. DISCUSSION: Surgical modality and tumor prognostic factors, however, seemed to play a minor role in patients' subjective QoL, which is discussed in terms of the "well-being paradox."

The German SUCCESS C Study - The First European Lifestyle Study on Breast Cancer.

SUMMARY: Cohort trials have shown evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients. The SUCCESS C study is the first European trial to evaluate the effect of an intensive lifestyle intervention program on disease-free survival in women with early breast cancer and to examine the predictive value of selected biomarker candidates. A total of 3,547 women with early-stage, Her2/neu-negative breast cancer will be included. The first randomization will compare disease-free survival in patients treated with either 3 cycles of FEC (epirubicine, fluorouracil, cyclophosphamide), followed by 3 cycles of docetaxel or 6 cycles of docetaxel-cyclophosphamide, and thus assess the role of anthracycline-free chemotherapy. The second randomization compares disease-free survival in patients with a body mass index of 24-40 kg/m(2) receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. In addition, the study will evaluate the predictive role of cancer-associated and obesity-related biomarkers for the prediction of disease recurrence and survival. This SUCCESS C trial will provide valuable information on the effects of a lifestyle intervention program on the prognosis of early breast cancer patients.

Worldwide first experiences with vacuum-assisted closure as alternative treatment method to repair defects of an extended thoracic wall recurrence of breast cancer.

INTRODUCTION: Loco-regional recurrences of the breast cancer are associated with a bad prognosis. Often costly autologous-tissue treatment as a surgery aiming at repairing the defects is necessary. PATIENTS AND METHODS: Four female patients were treated with the vacuum-assisted closure (VAC)-system in context with the recurrence resection. In all cases a primary local masking was not possible. RESULTS: In the described cases the wounds healed well during the post-operative phase. There occurred no problems either during the radiation treatment or during chemotherapy in the case of lying VAC-Systems. CONCLUSION: Using vacuum-assisted wound closure one can avoid autologous-tissue treatment in the case of extensive loco-regional recurrences.

Prospective multicenter randomized phase III study of weekly versus standard docetaxel (D2) for first-line treatment of metastatic breast cancer.

PURPOSE: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. METHODS: Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly [75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. RESULTS: Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia ≥grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to nonhematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). CONCLUSION: The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status.

Prospective multicenter randomized phase III study of weekly versus standard docetaxel plus doxorubicin (D4) for first-line treatment of metastatic breast cancer.

PURPOSE: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. METHODS: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age <65 years or a Karnofsky Performance Status of 70-100%. All patients in the D4 study received doxorubicin (50 mg/m(2)) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m(2) every 3 weeks (q3w) or at a weekly dose of 35 mg/m(2) (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. RESULTS: Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≥ grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). CONCLUSION: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.

Personality traits and psychosocial stress: quality of life over 2 years following breast cancer diagnosis and psychological impact factors.

OBJECTIVE: The aim of this study was to investigate changes in the quality of life (QoL) and body image among breast cancer patients over 2 years and to examine different predictive factors for QoL 2 years after the primary operation. METHODS: A total of 203 women with a primary diagnosis of breast cancer completed the questionnaires 2 weeks and 6, 12, 18, and 24 months after surgery. Quality of Life Questionnaire (QLQ-C30), Breast Cancer Specific Quality of Life Questionnaire Module (QLQ-BR23), Questionnaire on Stress in Cancer Patients (QSC-R23), Freiburg Personality Inventory (FPI-R), Life Orientation Test (LOT) were used as standardized measures. RESULTS: The overall QoL and most functional and symptom scales improved during the 2-year period. However, cognitive functioning, body image, and the three symptom scales of insomnia, constipation, and diarrhea did not change. Age was only capable of predicting physical functioning, whereas tumor size, axillary surgery, and adjuvant chemotherapy were not predictive of the long-term QoL functional scores. Initial distress was the most potent predictive factor for long-term QoL. Baseline functioning predicted functional QoL scores 2 years later. And higher scores for neuroticism were associated with a poorer QoL. However, optimism was not capable of predicting the QoL 2 years later. CONCLUSION: Screening measures should be implemented at the time when breast cancer is diagnosed, in order to identify psychologically vulnerable patients and offer them professional psycho-oncological help.

Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes.

PURPOSE: Effective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and effective in first-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Forty patients (median age 52 years) with MBC received the combination of oral VRL 60 mg/m(2) on days 1, 8 and 15 plus capecitabine 1,000 mg/m(2) bid given from day 1 to day 14 in an open-label, international, multicentre, phase II study. Cycles were repeated every 3 weeks. The primary endpoint was response rate (RR) evaluated by an independent panel review. Secondary objectives included safety, duration of response, progression-free survival, overall survival and quality of life. RESULTS: All the patients had received prior chemotherapy with anthracyclines and taxanes, 75% were refractory/resistant to anthracycline and/or taxane, 72.5% presented with visceral involvement and the last prior chemotherapy for 87.5% of the patients was for advanced disease setting. The median number of administered cycles per patient was 4 (range 1-31). Eight responses were documented and validated by an independent panel review, yielding RRs of 20% [95% CI: 9-35.6] in the intent-to-treat (treated) population and 23.5% [95% CI: 10.7-41.2] in the 34 evaluable patients. Median progression-free survival and median overall survival were 3.4 months [95% CI: 2.3-5.5] and 11.3 months [95% CI: 8.1-16.4], respectively. The principal toxicities were anaemia, neutropenia (rarely complicated; only one patient experienced febrile neutropenia), fatigue and gastrointestinal toxicities with very few grade 3-4 non-haematological toxicities. CONCLUSIONS: In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an efficacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients' population. Moreover, this well-tolerated combination offers the advantages of an all oral regimen.