Awareness, offer, and use of psychosocial services by breast cancer survivors in Germany: a prospective multi-centre study.

PURPOSE: This study examined the pattern of psychosocial care in breast cancer survivors. METHODS: In a prospective study with measurements before surgery, 1 month, 8 months, and 5 years thereafter, we examined the proportion of breast cancer survivors who were aware about, had been offered and received various types of psychosocial services from psychologists, social workers, doctors, self-help groups etc. The degree of helpfulness per service among users was ascertained with Likert scales. Determinants of awareness, offer and use were investigated using binary logistic regression analyses. How the services are inter-related was tested with principal component analyses. RESULTS: Among 456 breast cancer survivors who participated until 5 years, psychological services were known by 91%, offered to 68%, and used by 55% of patients. Social services were known by 86%, offered to 65%, and used by 51%. Women ≥ 65 years were less likely to be informed about (odds ratio (OR) 0.2) and get offers for psychosocial services (OR 0.4 for social and 0.5 for psychological services) than women < 65 years. The services rated most helpful were social services in the hospital, psychological counselling by a consultant and psychotherapy in private practices. CONCLUSION: These findings underline the importance of psychosocial support by physicians in addition to the "professional" mental health and social care providers. They also show that elderly women in need for support might be in danger of not being well-informed about the services available.

Association of social service counseling in breast cancer patients with financial problems, role functioning and employment-results from the prospective multicenter BRENDA II study.

BACKGROUND: This study examined the relationship between social service counseling (SSC) and financial and role functioning problems in primary breast cancer (BC) patients over a 5-year observation period. METHODS: In the multicenter prospective study, patients were approached before surgery (t1), before initiation of adjuvant treatment (t2), after therapy completion (t3), and 5 years after surgery (t4). We examined the proportion of BC survivors who had financial and role functioning problems and the proportion who were employed at t4. We examined how frequently patients were informed about, offered, or used SSC, and we used multivariate logistic regression analyses to examine the relationship between this and financial and role functioning problem prevalence. RESULTS: Of the 456 BC survivors, 33% had financial problems and 22% reported role functioning problems at t4. There was no evidence that women with increased financial problems were informed about SSC more often than those without (OR 1.1, p = 0.84) or that they used SSC more often (OR 1.3, p = 0.25). However, women with role functioning problems were informed about SSC significantly more often (OR 1.7, p = 0.02) and attended counseling significantly more often (OR 1.6, p = 0.03). Among participants aged < 65 years at t4 (n = 255), 70% were employed. Patients who had received SSC were more likely to be employed at t4 than patients who did not (OR 1.9, p = 0.04). CONCLUSION: These findings underline the importance of SSC for BC patients with role functioning issues. They indicate that individuals who use SSC are more likely to be employed later on than individuals who do not.

Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa).

PURPOSE: Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. METHODS: A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. RESULTS: After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85-1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88-1.25). CONCLUSIONS: Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

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.

Quality of life during and after adjuvant anthracycline-taxane-based chemotherapy with or without Gemcitabine in high-risk early breast cancer: results of the SUCCESS A trial.

PURPOSE: In high-risk early breast cancer, adjuvant taxane-Gemcitabine combinations result in a recurrence-free survival similar to single-agent taxanes. However, haematologic toxicities and need for dose reductions are more frequent in combinations. Which option ultimately provides a better quality of life (QoL) is unknown. We compared the QoL curves before, during, and up to one year after three cycles of Fluorouracil-epirubicin-cyclophosphamide followed by three cycles of Docetaxel-Gemcitabine or Docetaxel. METHODS: Overall, 3691 women with recent R0-resection of a primary epithelial breast cancer participated in the nationwide SUCCESS A clinical trial. The centres sent QoL questionnaires of the European Organisation for Research and Treatment of Cancer before and up to 15 months after randomisation to Docetaxel-Gemcitabine versus Docetaxel. Multilevel analysis by chemotherapy arm estimated the QoL time curves, questionnaire return, and dropout. RESULTS: The combination caused one-point higher global QoL (95% confidence ±1; p = 0.05) and 1.1 lower odds of adherence to the outcome (95% confidence 1.0-1.1; p = 0.23) than the monotherapy. In both groups, a 10-point decrease during therapy preceded a 16-point increase after chemotherapy (p < 0.001). The secondary QoL outcomes showed transient superiority of the combination at the end of chemotherapy. Discontinuation from chemotherapy and its reasons were equal in both groups. CONCLUSIONS: While patients perceive a one-point QoL difference as meaningless, a six-point increase is clinically relevant for them. That is, both regimens cause the same relevant long-term QoL improvement. With the similar recurrence-free survival, the lower toxicity, and the shorter chemotherapy duration in mind, taxanes without Gemcitabine are the preference. This challenges previous recommendations supporting combinations.

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.

Cardiac late events in German breast cancer patients: a validation study on the agreement between patient self-reports and information from physicians.

BACKGROUND: Self-administered health-status questionnaires are important tools in epidemiology. The objective of the presented validation study is to measure the agreement between breast cancer patients' self-reports and their physicians' information on late cardiac events, and to investigate determinants of agreement. To estimate possible misclassification is an important requirement for observational studies on cardiovascular endpoints. METHODS: A retrospective, multi-center cohort study included 11,982 women diagnosed with breast cancer in Germany in 1998-2008. In 2014, a questionnaire survey assessed cardiovascular risk factors and incident cardiac events after therapy. A validation study was conducted, based on a sample of 3091 breast cancer patients from two university hospitals. Among them, 2261 women (73%) sent back the questionnaire on cardiovascular events, and 1316 women gave consent to request medical records from their general practitioners. A total of 1212/1316 (92.1%) medical records could be obtained for validation. Cohen's kappa coefficient was calculated, and multivariate regression was applied to study the influence of patient characteristics on agreement between both data sources. RESULTS: Overall agreement for the composite endpoint of any cardiac event was 84.5% (kappa 0.35). Of 1055 breast cancer patients reporting no cardiac event, 950 (90%) had no such diagnosis in physicians' medical records. A total of 157 breast cancer survivors indicated a cardiac event, and the same diagnosis was confirmed by GPs for 74 (47%) women. For specific diagnoses, moderate to substantial agreement of self-reports was found for myocardial infarction (kappa 0.54) and stroke (kappa 0.61). Poor to fair agreement was present for angina pectoris, valvular heart disease, arrhythmia, and congestive heart failure. Younger age, higher education and a more recent cancer diagnosis were found to be associated with greater total agreement. CONCLUSIONS: For the composite endpoint, survivors of breast cancer report the absence of cardiac disease accurately. However, for specific diagnoses, self-reported morbidity data from breast cancer patients may not fully agree with information from physicians. The agreement is moderate for acute events like myocardial infarction and stroke, but poor to fair for chronic diseases.

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.

3D conformal radiotherapy is not associated with the long-term cardiac mortality in breast cancer patients: a retrospective cohort study in Germany (PASSOS-Heart Study).

PURPOSE: In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. In a retrospective cohort study, we investigated the long-term cardiac mortality risk of breast cancer survivors treated with modern RT in Germany. METHODS: A total of 11,982 women were included who were treated for breast cancer between 1998 and 2008. A systematic mortality follow-up was conducted until December 2012. The effect of breast cancer laterality on cardiac mortality and on overall mortality was investigated as a surrogate measure of exposure. Using Cox regression, we analyzed survival time as the primary outcome measure, taking potential confounding factors into account. RESULTS: We found no evidence for an effect of tumor laterality on mortality in irradiated patients (N = 9058). For cardiac mortality, the hazard ratio was 0.94 (95% CI 0.64-1.38) for left-sided versus right-sided tumors. For all causes of death, the hazard ratio was 0.95 (95% CI 0.85-1.05). A diagnosis of cardiac illness prior to breast cancer treatment increased both cardiac mortality risk and overall mortality risk. CONCLUSIONS: Contemporary RT seems not to be associated with an increased risk of cardiac mortality or overall mortality for left-sided breast cancer relative to right-sided RT. However, an extended follow-up period and exact dosimetry might be necessary to confirm this observation.

Self-reported long-term cardiac morbidity in breast cancer patients: a retrospective cohort study in Germany (PASSOS Heart Study).

PURPOSE: Improved survival after locoregional breast cancer has increased the concern about late adverse effects after therapy. In particular, radiotherapy was identified as a risk factor for major cardiac events in women treated until the 1990s. While modern radiotherapy with computerized planning based on 3D-imaging can help spare organs at risk, heart exposure may remain substantial. In a retrospective cohort study of women treated for locoregional breast cancer, we investigated whether current radiotherapy is associated with an elevated long-term cardiac morbidity risk. METHODS: The study included 11,982 women diagnosed with breast cancer in Germany in 1998-2008. After an individual mortality follow-up, 9338 questionnaires on cardiac events before or after therapy and on associated risk factors were sent out in 2014. Based on 4434 questionnaires from women with radiotherapy, we used Cox regression to analyze the association between self-reported cardiac morbidity and breast cancer laterality as a surrogate measure of radiation exposure. RESULTS: After a median follow-up of 8.3 years, there was no significant association of tumor laterality with cardiac morbidity in irradiated patients (458 events, hazard ratio for left-sided vs. right-sided tumors 1.07, 95% CI 0.89-1.29). Significant risk factors for any cardiac event included age at diagnosis, chemotherapy, hypertension, hypercholesteremia, and chronic kidney disease. CONCLUSIONS: For contemporary radiotherapy, we found no evidence for a significantly elevated cardiac morbidity risk in left-sided versus right-sided breast cancer. Possible reasons for failing to confirm earlier reports on increased risk include shorter follow-up, application of newer radiotherapy techniques, and improved health monitoring.

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.

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.

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.

The course of psychiatric co-morbidity in patients with breast cancer--results from the prospective multi-centre BRENDA II study.

PURPOSE: This study examined the frequency of psychiatric co-morbidity in patients with breast cancer, its changes over time and predictors for these changes. METHODS: In a prospective study with measurements before surgery (t1, baseline), 1 month (t2) and 8 months thereafter (t3) using the Patient Health Questionnaire, we examined the course of psychiatric co-morbidity in breast cancer patients. The co-morbidity courses were grouped into healthy (no co-morbidity during the study), acute (co-morbidity at t1 and/or t2, but not at t3), emerging (no co-morbidity at t1, but at t3) and chronic (co-morbidity at t1 and t3). RESULTS: Of the 598 participants, 19% had acute, 10% emerging and 9% chronic psychiatric co-morbidity. Acute co-morbidity was more common in patients with poor quality of life (odds ratio (OR) 9.6, 95% confidence interval (CI) 4.4-20.8) and somatic co-morbidity (OR 3.8, CI 1.1-12.4). Patients who perceived support from their doctors had acute co-morbidity less frequently (OR 0.7, CI 0.5-1.0). Emerging co-morbidity occurred more often in younger patients (OR 2.4, CI 1.2-4.7) and in patients with another cancer in their own (OR 2.0, CI 1.1-3.9) or family (OR 2.1, CI 1.1-4.3) histories, less often in patients with support from doctors (OR 0.6, CI 0.4-1.0). Chronic co-morbidity was related to poor quality of life (OR 12.1, CI 3.6-39.9). CONCLUSION: We found acute and emerging psychiatric co-morbidities less often in patients who reported having a supportive doctor-patient relationship. Patients that require psycho-oncological support often have poor quality of life and have experienced cancer before. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Do T1a breast cancers profit from adjuvant systemic therapy? A multicenter retrospective cohort study of 325 T1a-patients.

UNLABELLED: Small tumor size (≤5 mm, T1a) carries an excellent prognosis. Controversy exists over the extent of the variety of treatment approaches. We therefore explored the effect of adjuvant systemic therapy (AST) on recurrence free survival (RFS) and overall survival (OAS) for the group of T1a-tumors. METHODS: The multicenter study population included 9625 early breast cancer patients, diagnosed between 1992 and 2008. 5196 patients were T1 (54.0 %) and 325 of these patients (3.4 %) were T1a. RESULTS: Compared to patients with AST RFS and OAS were significantly worse for patients who did not receive AST (RFS: p = 0.001; OAS: p = 0.021). Even N0-T1a-patients (n = 279) significantly profited from AST (RFS: p = 0.001; OAS: p = 0.006). Patients with at least one poor prognostic factor (HR-, HER2+, N1 or G3) without AST also showed a significantly worse outcome (RFS: p = 0.026; OAS: p = 0.024) compared to pT1a-patients with AST. Consensus guidelines state that the prognosis of patients with T1a that are N0 is uncertain even if HER2 is amplified or overexpressed. In our study nodal-negative (N0) T1a-patients (n = 279) without AST showed a significantly worse RFS (p = 0.001), and a significantly worse OAS (p = 0.006) compared to those patients with AST. In multivariate analysis even after adjusting by age, grading, hormonal receptor status, HER2/neu-status and nodal status T1a-patients without AST were associated with a significantly worse RFS resp. OAS compared to patient with AST (RFS: p = 0.002; OAS: p = 0.007). CONCLUSIONS: There is an association between AST and improved RFS or OAS for breast cancer patients with T1a tumors.

The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial.

INTRODUCTION: Obese breast cancer patients have worse prognosis than normal weight patients, but the level at which obesity is prognostically unfavorable is unclear. METHODS: This retrospective analysis was performed using data from the SUCCESS A trial, in which 3754 patients with high-risk early breast cancer were randomized to anthracycline- and taxane-based chemotherapy with or without gemcitabine. Patients were classified as underweight/normal weight (body mass index (BMI) < 25.0), overweight (BMI 25.0-29.9), slightly obese (BMI 30.0-34.9), moderately obese (BMI 35.0-39.9) and severely obese (BMI ≥ 40.0), and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated (median follow-up 65 months). In addition, subgroup analyses were conducted to assess the effect of BMI in luminal A-like, luminal B-like, HER2 (human epidermal growth factor 2)-positive and triple-negative tumors. RESULTS: Multivariate analyses revealed an independent prognostic effect of BMI on DFS (p = 0.001) and OS (p = 0.005). Compared with underweight/normal weight patients, severely obese patients had worse DFS (hazard ratio (HR) 2.70, 95 % confidence interval (CI) 1.71-4.28, p < 0.001) and OS (HR 2.79, 95 % CI 1.63-4.77, p < 0.001), while moderately obese, slightly obese and overweight patients did not differ from underweight/normal weight patients with regard to DFS or OS. Subgroup analyses showed a similar significant effect of BMI on DFS and OS in patients with triple-negative breast cancer (TNBC), but not in patients with other tumor subtypes. CONCLUSIONS: Severe obesity (BMI ≥ 40) significantly worsens prognosis in early breast cancer patients, particularly for triple-negative tumors. TRIAL REGISTRATION: Clinicaltrials.gov NCT02181101 . Registered September 2005.

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.