Survivors of primary breast cancer 5 years after surgery: follow-up care, long-term problems, and treatment regrets. Results of the prospective BRENDA II-study.

PURPOSE: This study aims to answer the questions where breast cancer patients in Germany receive follow-up care (with what types of doctors) and what are the long-term problems and treatment regrets of breast cancer patients. METHODS: In the prospective multicenter cohort study BRENDA II ("Breast Cancer under Evidence-Based Guidelines"), 456 patients with primary breast cancer were sampled consecutively over a period of 4 years (2009-2012) and contacted again 5 years after surgery. Long-term problems were elicited on a 4-point Likert scale ranging from 0 ('not at all') to 3 ('very much'). RESULTS: 82% of the patients receive follow-up (FU) at the private practice gynecologist. In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner does this (multiple answers possible). Long-term problems attributed to the treatment were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94). Most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was most often for endocrine therapy (5%) and chemotherapy (4%). CONCLUSION: In Germany, different specialists are involved in the patients' FU care for BC. The detection of long-term problems due to BC treatment is an essential part of FU care.

Does the number of removed axillary lymphnodes in high risk breast cancer patients influence the survival?

BACKGROUND: The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed? METHODS: A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines. RESULTS: 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy. CONCLUSION: The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients.

Association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer: Results from the prospective multicenter BRENDA II study.

BACKGROUND: This study examined the association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer. PATIENTS AND METHODS: In the prospective multicenter cohort study BRENDA II, patients aged ≥65 years with primary breast cancer were sampled over a period of 4 years (2009-2012). A multiprofessional team (tumor board) discussed recommendation for adjuvant chemotherapy according to the German S3 guideline. Cognitive impairment was screened by the clock-drawing test (CDT) prior to adjuvant treatment. RESULTS: Two hundred and sixty-three patients were included in the study and CDT data were available for 193 patients. Thirty-one percent of the patients had cognitive impairment with different degree of severity. In high-risk patients (n = 61) tumor board recommendation in favor of chemotherapy was 90% and in intermediate-risk patients (n = 170) 27%. Not receiving recommendation for chemotherapy in spite of guideline recommendation was more frequent in patients with cognitive impairment (67%) vs patients without cognitive impairment (46%) with P = 0.02 (OR 2.4, 95% confidence interval (CI) 1.2-4.9). Age, education, migration background and comorbidities were not associated with chemotherapy recommendation by the tumor board among cognitively impaired patients. Once the tumor board had recommended chemotherapy, application of chemotherapy was similar in both groups of patients with or without cognitive impairment. CONCLUSION: Almost one third of older patients with breast cancer are affected by cognitive impairment prior to adjuvant treatment. In these patients, cognitive impairment was associated with tumor board decision against chemotherapy in spite of a positive guideline recommendation.

Comorbidity-dependent adherence to guidelines and survival in breast cancer-Is there a role for guideline adherence in comorbid breast cancer patients? A retrospective cohort study with 2137 patients.

In the treatment of breast cancer, decisions on adjuvant treatment reflect individual patient characteristics like age and comorbidity. This study assessed the association between adherence to guidelines for adjuvant treatment and survival while taking into account age at diagnosis and comorbidities. We collected the Charlson comorbidity index at baseline for 2179 women treated for primary breast cancer from 1992 to 2008 who participated in a German retrospective multicenter cohort study. We assessed subsequent adjuvant therapy guideline adherence and survival in relation to baseline comorbidities. Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in patients with higher Charlson score. Patients with higher Charlson scores received chemotherapy and radiotherapy less often and had higher rates of mastectomy. Irrespective of comorbidity (Charlson score 0, 1-2, ≥3), patients with 100% guideline-adherent adjuvant treatment showed better overall and disease-free survival (DFS) compared to patients with guideline violations (GVs). Controlling for age, comorbidity and tumor characteristics, the hazard ratio for at least one GV was 1.65 (95% confidence interval [CI]: 1.33-2.07) for overall survival and 1.84 (95% CI: 1.53-2.22) for DFS. Guideline-adherent treatment was significantly less frequent in comorbid patients, although guideline adherence was strongly associated with improved survival, irrespective of severity, and number of comorbid diseases.

Is extracapsular nodal extension in sentinel nodes a predictor for nonsentinel metastasis and is there an impact on survival parameters?-A retrospective single center cohort study with 324 patients.

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2 mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.

A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study.

PURPOSE: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). METHODS: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). RESULTS: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838-1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31). CONCLUSION: Both PLD and capecitabine are effective first-line agents for MBC.

Are There Breast Cancer Patients with Node-Negative Small Tumours, Who Do Not Benefit from Adjuvant Systemic Therapy?

OBJECTIVE: To identify subgroups of patients with pT1 pN0 breast cancer (BC) who might not profit from adjuvant systemic therapy (AST). METHODS: Data of 3,774 pT1 pN0 BC patients from 17 certified BC centres within the BRENDA study group were collected between 1992 and 2008 and retrospectively analysed. Uni- and multivariate analyses were performed using Kaplan-Meier methods and Cox regression models. RESULTS: 279 (7.4%) of the pT1 pN0 BC patients were T1a, 944 (25.0%) were T1b and 2,551 (67.6%) were T1c. There was no significant difference (p > 0.1) in recurrence-free survival (RFS)/overall survival (OAS) between patients with pT1a, pT1b, and T1c. Patients receiving any type of AST had a better outcome compared to women without AST after adjusting for age, tumour size, and intrinsic subtypes (RFS: p < 0.001; OAS: p < 0.001). AST was the most important prognostic parameter for RFS followed by intrinsic subtypes and age. CONCLUSION: Patients with pT1 pN0 BC profit from AST independently of molecular subtypes, tumour size, age or comorbidity, with 5-year RFS of more than 95%. The correct definition of subgroups of patients who do not need AST is still an open question.

Pattern of metastatic spread and subcategories of breast cancer.

PURPOSE: The development of metastases is the most aggressive attribute of breast cancer. In this retrospective multicenter study, we evaluated if and how the different pathological breast cancer subtypes influence the spreading of tumor cells, the development of metastasis and the survival of breast cancer patients. METHODS: This retrospective German multicenter study is based on the BRENDA collective including 9625 breast cancer patients treated in the adjuvant setting. We used the χ 2 tests for the analysis of the categorical variables between groups of patients with different sites of metastasis. Survival distributions and median survival times were estimated using the Kaplan-Meier product-limit method. The log-rank test was applied to compare survival rates. The Cox proportional hazards model was used to estimate the hazard ratio and confidence intervals. RESULTS: 886 women developed metastases during a time interval of 53 months after primary diagnosis. Luminal A tumor patients were more likely to get bone metastases than lung, liver or CNS metastases. Patients with a triple-negative subtype were, however, the least affected by metastasis in the skeleton. They were most likely to develop visceral metastases. Location, numbers of metastases herein and the subtype influenced the overall survival (OAS). Altogether, the best OAS was found in patients with the luminal A subtype, the worst in patients with the triple-negative subtype. CONCLUSIONS: Knowledge of the typical metastatic pattern of the subtypes of breast cancer will help to personalize therapeutic options and follow-up examinations of cancer patients.

The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients.

BACKGROUND: Mammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study. METHODS: We retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup. RESULTS: Overall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p < 0.01). For invasive lobular cancers, the mammography showed better correlation with histology than ultrasound (p = 0.01), whereas there was no such advantage for invasive ductal cancers. Ultrasound was significantly superior for HR negative cancers (p < 0.001). HER2/neu positive cancers were also more precisely assessed by ultrasound (p < 0.001). The size of HER2/neu negative cancers could be more accurately predicted by mammography (p < 0.001). CONCLUSION: This multicentered health services research approach demonstrates that predicting tumor size by mammography and ultrasound provides accurate results. Biological tumor features do, however, affect the diagnostic precision.

Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer.

BACKGROUND: The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. METHODS: This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms "exhausted CHAID (Chi-square Automatic Interaction Detectors)" and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. RESULTS: Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 % CI: 3.52-15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 % CI: 1.36-6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases. CONCLUSION: The bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases.

Exploring patient- and physician-related factors preventing breast cancer patients from guideline-adherent adjuvant chemotherapy-results from the prospective multi-center study BRENDA II.

BACKGROUND: This study examined which patient- and physician-related factors influence guideline violations in adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective multi-center cohort study, patients with primary breast cancer were sampled consecutively over a period of four years (2009-2012). Patients completed a questionnaire prior to surgery and prior to adjuvant therapy. This questionnaire assessed health-related quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, psychiatric co-morbidity with the Patient Health Questionnaire (PHQ), demographic characteristics (age, education), and the intensity of fear for chemotherapy. After surgery, a multi-professional team discussed recommendation for adjuvant chemotherapy, and this decision was documented in a database together with the indication for chemotherapy according to the German S3 guideline. This multi-professional team was blinded to that algorithm-based decision. Six months later, it was documented whether the patient had received adjuvant chemotherapy or not. RESULTS: Altogether, 857 patients were included in the study. In 391 of these patients, the tumor board (TB) decided to recommend chemotherapy. The most important reasons for not recommending chemotherapy were somatic co-morbidity not allowing adjuvant chemotherapy and age >75 years. Of these 391 patients, 73 (19 %) patients eventually did not receive chemotherapy. Deviations from the initial therapy decision were more frequent in older patients (≥75 years) with poor QoL. If the QoL was good, higher age was not related to deviation. There was some evidence that patients with higher education less frequently received chemotherapy (CT). Furthermore, if patients were very afraid of chemotherapy, deviations from the initial therapy decision were more likely. Co-morbidity and fear of CT were not related to the likelihood of deviating from the initial therapy decision. CONCLUSION: Nineteen percent of patients eventually did not receive chemotherapy, despite guideline and TB recommendations. In these patients, this mainly occurred in association with poor QoL in elderly patients >75 years old. In the group with a chemotherapy recommendation, patients' fear of chemotherapy is another factor preventing patients from undergoing adjuvant chemotherapy.

Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer.

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer. METHODS: We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk. RESULTS: Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P=0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P=0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P=1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications. CONCLUSIONS: The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.).

Guidelines are advantageous, though not essential for improved survival among breast cancer patients.

The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100% guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95% CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95% (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100% guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.

Does patient education work in breast cancer? Final results from the global CARIATIDE study.

AIM: To determine the impact of educational materials (EMs) on the treatment compliance of postmenopausal women with hormone receptor-positive (HR+) early-stage breast cancer. PATIENTS & METHODS: Patients (n = 2757) were randomized to standard aromatase inhibitors (AI) alone (group A) or with EMs (group B) in a global, real-world setting. RESULTS: The 2-year results (n = 2242) showed EMs had no impact on compliance (82 vs. 82%, group A vs. B), compliance with initial AI (82 vs. 81%) or persistence (90 vs. 88%), confirming the 1-year interim analysis (n = 2567). Of the 2082 patients considered compliant at 1 year, 77% remained compliant at 2 years. Discontinuations (9%) were mainly attributed to AI-related side effects (68% of discontinuations). Exploratory analyses suggest a relationship between patient characteristics and compliance behaviors. CONCLUSION: EMs do not improve compliance in this patient population. Compliance and persistence are complex end points influenced by multiple variables. Side effects were the main reasons for discontinuations.

Predicting fatigue in older breast cancer patients receiving radiotherapy. A head-to-head comparison of established assessments.

OBJECTIVES: Because of substantial toxicities in older adults, chemotherapy is often omitted while the frequency of radiotherapy changes only minimally. In this study, we addressed the value of different assessments for predicting fatigue after radiotherapy in older breast cancer patients. PATIENTS AND METHODS: We included 74 women with primary breast cancer over the age of 65 years treated with radiotherapy (26 % with additional chemotherapy). Assessments were conducted before adjuvant treatment and after radiotherapy. The assessments included the Vulnerable Elders Survey (VES-13), the Karnofsky Performance Status (KPS), the EORTC Quality of Life assessment (EORTC-QLQ-C30), a cancer-specific comprehensive geriatric assessment (cancer-specific CGA), and the Fried frailty score. Multiple linear regression analyses were used to assess correlations with the FACIT-fatigue scale. RESULTS: Patients were on average 71 years old (range, 65-86 years). Most tumors (n=62) were classified as intermediate risk according to the St. Gallen consensus. The cancer-specific CGA was best associated with fatigue (p < 0.001, ß estimate = 1.75), followed by the Fried frailty score (for the score of 1 versus reference of 2 and higher: p = 0.035, ß estimate = - 5.74). There were no significant ceiling effects but there were substantial floor effects for the VES-13, KPS, and frailty score. CONCLUSION: The cancer-specific CGA and the Fried frailty score (driven mainly by the item "exhaustion") outperformed the other indices in predicting fatigue in a group of rather well-functioning older women with primary breast cancer.

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients.

BACKGROUND: The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL). METHODS: Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data. RESULTS: Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm. CONCLUSION: No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid.

Work-life balance of German gynecologists: a web-based survey on satisfaction with work and private life.

PURPOSE: Work-life balance is an upcoming issue for physicians. The working group "Family and Career" of the German Society for Gynecology and Obstetrics (DGGG) designed a survey to reflect the present work-life balance of female and male gynecologists in Germany. METHODS: The 74-item, web-based survey "Profession-Family-Career" was sent to all members of the DGGG (n = 4,564). In total, there were 1,036 replies (23%) from 75% female gynecologists (n = 775) aged 38 ± 7 (mean ± standard deviation [SD]) years and 25% male (n = 261) gynecologists aged 48 ± 11 years. Statistical analyses were performed using the mean and SD for descriptive analysis. Regression models were performed considering an effect of p ≤ 0.05 as statistically significant. RESULTS: 47% women and 46% men reported satisfaction with their current work-life balance independent of gender (p(gender) = 0.15). 70% women and 75 % men answered that work life and private life were equally important to them (p(gender) = 0.12). While 39% women versus 11% men worked part-time (p gender < 0.0001), men reported more overtime work than women (p(gender) < 0.0001). 75 % physicians were not satisfied with their salary independent of gender (p(gender) = 0.057). Work life affected private life of men and women in a similar way (all p(gender) > 0.05). At least 37% women and men neglected both their partner and their children very often due to their work. CONCLUSIONS: Female physicians often described their work situation similar to male physicians, although important differences regarding total work time, overtime work and appreciation by supervisors were reported. Work life affected private life of women and men in a similar way.

Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9,156 patients.

BACKGROUND: Triple-negative breast cancer (TNBC) remains a challenging topic for clinical oncologists. This study sought to evaluate TNBC versus other breast cancer subtypes with respect to survival parameters. We evaluated possible differences in survival in TNBC by age and by the extent to which evidence-based treatment guidelines were adhered. METHODS: This German retrospective multi-center cohort study included 9156 patients with primary breast cancer recruited from 1992 to 2008. RESULTS: The rates of guideline adherence are significantly lower in TNBC compared to non-TNBC subtypes. These lower rates of guideline adherence can be observed in all age groups and are most pronounced in the >65 subgroup [<50 (20.9% vs. 42.0%), 50-64 (25.1% vs. 51.1%), and >65 (38.4% vs. 74.6%)]. In TNBC patients of all age groups, disease-free survival and overall survival were associated with an improvement by 100% guideline-adherent adjuvant treatment compared to non-adherence. Furthermore, TNBC patients of all ages had similar outcome parameters if 100% guideline-adherent adjuvant treatment was applied. CONCLUSION: The rates of guideline-adherent treatment were significantly lower in TNBC, even though guideline adherence was strongly associated with improved survival. In the case of 100% guideline-adherent treatment, no difference in survival was observed over all the age groups examined, even in the group of >65-year-old TNBC patients.

The power of DNA double-strand break (DSB) repair testing to predict breast cancer susceptibility.

Most presently known breast cancer susceptibility genes have been linked to DSB repair. To identify novel markers that may serve as indicators for breast cancer risk, we performed DSB repair analyses using a case-control design. Thus, we examined 35 women with defined familial history of breast and/or ovarian cancer (first case group), 175 patients with breast cancer (second case group), and 245 healthy women without previous cancer or family history of breast cancer (control group). We analyzed DSB repair in peripheral blood lymphocytes (PBLs) by a GFP-based test system using 3 pathway-specific substrates. We found increases of microhomology-mediated nonhomologous end joining (mmNHEJ) and nonconservative single-strand annealing (SSA) in women with familial risk vs. controls (P=0.0001-0.0022) and patients with breast cancer vs. controls (P=0.0004-0.0042). Young age (<50) at initial diagnosis of breast cancer, which could be indicative of genetic predisposition, was associated with elevated SSA using two different substrates, amounting to similar odds ratios (ORs=2.54-4.46, P=0.0059-0.0095) as for familial risk (ORs=2.61-4.05, P=0.0007-0.0045). These findings and supporting validation data underscore the great potential of detecting distinct DSB repair activities in PBLs as method to estimate breast cancer susceptibility beyond limitations of genotyping and to predict responsiveness to therapeutics targeting DSB repair-dysfunctional tumors.