Financial difficulties in breast cancer survivors with and without migration background in Germany-results from the prospective multicentre cohort study BRENDA II.

PURPOSE: We aimed to explore the trajectory of financial difficulties among breast cancer survivors in the German health system and its association with migration background. METHODS: In a multicentre prospective study, breast cancer survivors were approached four times (before surgery, before and after adjuvant therapy, five years after surgery) and asked about their migration history and financial difficulties. Migrants were defined as born/resided outside Germany or having citizenship/nationality other than German. Financial difficulties were ascertained with the financial difficulties item of the European Organisation for Research and Treatment of Cancer Core Instrument (EORTC QLQ-C30) at each time-point (cut-off > 17). Financial difficulties were classified in trajectories: always (every time-point), never (no time-point), initial (first, not fourth), delayed (only fourth), and acquired (second and/or third, not first). A logistic regression was conducted with the trajectories of financial difficulties as outcome and migration background as exposure. Age, trends in partnership status, and educational level were considered as confounders. RESULTS: Of the 363 participants included, 49% reported financial difficulties at at least one time-point. Financial difficulties were reported always by 7% of the participants, initially by 5%, delayed by 10%, and acquired by 21%. Migrants were almost four times more likely to report delayed (odds ratio [OR] = 3.7; 95% confidence interval [CI] 1.3, 10.5) or acquired (OR = 3.6; 95% CI 1.6, 8.4) financial difficulties compared to non-migrant participants. CONCLUSION: Survivors with a migration background are more likely to suffer from financial difficulties, especially in later stages of the follow-up. A linguistically/culturally competent active enquiry about financial difficulties and information material regarding supporting services/insurances should be considered.

To which extent do breast cancer survivors feel well informed about disease and treatment 5 years after diagnosis?

OBJECTIVE: In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. METHODS: In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. RESULTS: There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (ß 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (ß - 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (ß -0.34, p 0.03) and by immigrants (ß -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (ß 0.19/0.19/0.20/0.25; each p < 0.01). CONCLUSION: Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST).

Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included. Univariable/multivariable analyses were performed for 13 clinical/pathological parameters to predict a positive pathological axillary status after chemotherapy using logistic regression models. Odds ratios and 95%-confidence-intervals were reported. Model performance was assessed by leave-one-out cross-validation. Calculations were performed using the SAS Software (Version 9.4, SAS Institute Inc., Cary, NC, USA). 369 of 553 patients in Arm C were included in multivariable analysis. Stepwise backward variable selection based on a multivariable analysis resulted in a model including estrogen receptor (ER) status (odds ratio (OR) 3.916, 95% confidence interval (CI) 2.318-6.615, p < 0.001), multifocality (OR 2.106, 95% CI 1.203-3.689, p = 0.0092), lymphovascular invasion (OR 9.196, 95% CI 4.734-17.864, p < 0.001), and sonographic tumor diameter after PST (OR 1.034, 95% CI 1.010-1.059, p = 0.0051). When validated, our model demonstrated an accuracy of 70.2% using 0.5 as cut-point. An area under the curve of 0.81 was calculated. The use of individual parameters as predictors of lymph node status after chemotherapy resulted in an inferior accuracy. Our model was able to predict the probability of a positive axillary nodal status with a high accuracy. The use of individual parameters showed reduced predictive performance. Overall, tumor biology was the strongest parameter in our models.

Predictors of the course of quality of life during therapy in women with primary breast cancer.

PURPOSE: Multimodal therapies affect the quality of life (QoL) of patients with primary breast cancer (PBC). The objectives of this prospective study were to explore the changes in QoL from diagnosis to conclusion of adjuvant therapy and to identify predictive factors of QoL. METHODS: Before surgery (t1), before onset of adjuvant treatment (t2) and after completion of adjuvant chemo- or radiotherapy (t3), patients with PBC (n = 759) completed the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire, Charlson Comorbidity Index, Patient Health Questionnaire and Perceived Involvement in Care Scales. Predictors of the course of global QoL were estimated using multinomial logistic regression. Effect estimates are odds ratios (OR) and their 95% confidence intervals (CIs). RESULTS: Global QoL improved between t1 and t3, while physical functioning, emotional functioning and fatigue deteriorated. QoL before surgery was more often poor in patients <60 years (OR 2.2, 95% CI 1.5-3.1) and in those with comorbid mental illnesses (OR 8.6, CI 5.4-13.7). Forty-seven percentage reported good global QoL both at t1 and at t3. QoL improved in 28%, worsened in 10% and remained poor in 15%. Compared to patients with consistently good global QoL, a course of improving QoL was more often seen in patients who had received a mastectomy and in those with intense fear of treatment before surgery. A course of decreasing QoL was more often found in patients who were treated with chemotherapy. QoL stayed poor in patients with chemotherapy, mastectomy and intense fear. There was no evidence that radiotherapy, progressive disease or perceived involvement impact the course of QoL. CONCLUSIONS: Younger age and comorbid mental illnesses are associated with poor QoL pre-therapeutically. QoL is more likely to stay or become poor in patients who receive chemotherapy.

Identifying the impact of inflammatory breast cancer on survival: a retrospective multi-center cohort study.

PURPOSE: Inflammatory breast cancer (IBC) represents a rare and aggressive form of cancer with negative prognosis and high rate of recurrence. The purpose of this retrospective multi-center study was to evaluate the effect of IBC on overall and disease-free survival. Furthermore we analyzed the influence of hormone and Her2 receptor expression on inflammatory breast cancer cells on the clinical outcome of patients. METHODS: This retrospective German multi-center study included 11,780 patients with primary breast cancer recruited from 1992 to 2008. In this sub-group analysis we focused on 70 patients with IBC. RESULTS: Despite the relatively small sample size, we could confirm the aggressiveness of inflammatory breast cancer and the different clinical behavior of IBC subtypes. It could be demonstrated that the lack of expression of hormone receptors on tumor cells is associated with a more aggressive clinical course and decreased overall and disease-free survival. Higher incidence of Her2 overexpression, that is typically associated with poor prognostic outcome among women with non-IBC tumors, seems however to have no prognostic significance. CONCLUSIONS: This BRENDA sub-group analysis, on a German cohort of breast cancer patients confirmed the negative outcome of IBC and the different clinical behavior of IBC subtypes. The best management of IBC requires intensive coordination and cooperation between various clinical disciplines involved in the treatment of IBC patients. Moreover there is a need to identify IBC-specific targeted therapies to improve the curing prospects of this subtype of cancer.

Is guideline-adherent adjuvant treatment an equal alternative for patients aged >65 who cannot participate in adjuvant clinical breast cancer trials? A retrospective multi-center cohort study of 4,142 patients.

INTRODUCTION: It is well accepted that innovation in oncology is transported through randomized clinical trials (CT), furthermore there is some evidence that patients profit from participation in CT. However, especially elderly patients aged >65 usually do not have access to clinical trials; we therefore used an unselected patient cohort to investigate the following questions: (1) Is there a difference in survival parameters between study participants <65 and elderly 65-80 non-participants? (2) Is guideline-adherent adjuvant treatment an equal alternative for elderly patients aged 65-80? MATERIALS AND METHODS: This German retrospective multi-center cohort study included 4,142 patients (study participants <65 and elderly breast cancer patients 65-80) with primary breast cancer recruited from 1992 to 2008 in 17 participating breast cancer centers. RESULTS: Applying the exclusion criteria, we included 960 (23.2%) study participants (PA) <65 and 3,182 (76.8%) elderly >65. Elderly non-participants (NPA) >65 demonstrate a significantly inferior RFS [RFS: HR = 1.67; p < 0.001] and OS [OS: HR = 1.98; p < 0.001] compared to PA <65. Within the elderly group, 1,868 (58.7%) patients received guideline-adherent adjuvant treatment. When comparing guideline conform elderly >65 versus PA <65, we found no significant difference in RFS [RFS: HR = 1.17; p = 0.218] and OS [OS: HR = 1.34; p = 0.054]. In contrast, non-guideline-adherent elderly demonstrated significantly inferior survival parameters [RFS: HR = 2.06; p < 0.001] [OS: HR = 2.50; p < 0.001] compared to <65 PA. CONCLUSION: Guideline-adherent adjuvant treatment seems to be an equivalent option for elderly breast cancer patients. There is a strong association between guideline adherence and improved outcome parameters in elderly breast cancer patients.

Assessing the impact of CMF-like/Anthracycline-based/Anthracycline-Taxane-based/dose-dense chemotherapy in dependency of positive axillary lymph nodes/hormone receptor-status/grading/T-stage on survival - A retrospective multi-centre cohort study of 3677 patients receiving adjuvant chemotherapy.

AIM: Adjuvant chemotherapy has changed dramatically in the last decades. Anthracycline-/Taxane-based and dose-dense chemotherapy regimens improved survival in node positive breast cancer. This study tries to answer the following questions: METHODS: This is a German multi-centre (17 participating hospitals all certified as breast cancer centres) retrospective cohort study. We included patients that received CMF-like (CMF) (n=1308), Anthracycline-based (A) (1046), Anthracycline-Taxane-based (AT) (1110) and dose-dense chemotherapy (DD) (213) into this analysis. RESULTS: In case of N0 and 1-3 pos LN we did not observe statistically significant differences in overall (OS) and disease-free survival (DFS) between CMF/A/AT and (for 1-3 pos LN) DD. In the group of 4-10 pos LN we observe an improvement by the use of AT-based chemotherapy, which cannot further be improved by DD chemotherapy. However in the highest risk group, defined as ⩾11 pos LN, we observed a statistically significant improvement in survival by the use of DD chemotherapy. Also a statistically slightly non-significant trend towards improvement of survival parameters by the use of DD compared to AT chemotherapy could be observed. Only for G3 subtypes we could observe a survival benefit for DD. These results remain consistent after exclusion of non-guideline adherent patients (surgery, radiotherapy and endocrine therapy) in order to reduce the bias of guideline violations in other adjuvant treatment modalities. CONCLUSION: DD chemotherapy is associated with improved survival parameters in patients with ⩾11 positive LN.

The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects.

BACKGROUND: Radiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients: 1. Does guideline-adherent RT improve primary breast cancer patient survival? 2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters? 3. Does adjuvant RT compensate for an incomplete tumor resection (R1)? PATIENTS AND METHODS: In this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines. RESULTS: The patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613]. CONCLUSION: Our study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.

Comparing the outcome between multicentric and multifocal breast cancer: what is the impact on survival, and is there a role for guideline-adherent adjuvant therapy? A retrospective multicenter cohort study of 8,935 patients.

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, and their outcomes have been compared with unifocal (UF) tumors. We attempted to answer the following questions: (1) Does MF/MC presentation influence the outcome concerning BC mortality?, (2) Is there an impact of guideline-adherent adjuvant treatment in these BC subtypes?, and (3)What is the influence of guideline violations concerning surgery (breast-conserving surgery versus mastectomy) on the survival of MF/MC BC patients? Between 1992 and 2008, we retrospectively analyzed 8,935 breast cancer patients from 17 participating breast cancer centers within the BRENDA study group. Of 8,935 breast cancer patients, 7,073 (79.2 %) had UF tumors, 1,398 (15.6 %) had MF tumors, and 464 (5.2 %) had MC tumors. RFS was significantly worse for MF/MC BC patients compared to patients with UF tumors (MF p = 0.007; MC p = 0.019). OAS was significantly worse for MC patients but not for MF patients compared to patients with UF tumors (MF p = 0.321; MC p = 0.001). Guideline adherence was significantly lower in patients with MF (n = 580; 41.5 %) and MC (n = 204; 44.0 %) compared to patients with UF (n = 3,871; 54.7 %) (p < 0.001) tumors. Guideline violations were associated with a highly significant deterioration in survival throughout all subgroups except for MC, with respect to RFS and OAS. For 100 %-guideline-adherent patients, we could not find any significant differences in RFS and OAS after adjusting by nodal status, grade, and tumor size. Furthermore, we could not find any significant differences in RFS and OAS in patients with MF or MC stratified by breast-conserving therapy (BCT lumpectomy and radiation therapy) and mastectomy. There is a strong association between improved RFS and OAS in patients with MF/MZ BC. There are no significant differences in RFS and OAS for patients with breast-conserving therapy or mastectomy.

Trends in patient characteristics, treatment and survival in breast cancer in a non-selected retrospective clinical cohort study of 2,600 patients.

PURPOSE: Breast cancer epidemiology and survival recently saw major changes resulting from improved screening and treatment modalities. This paper aims to provide an overview of changes in recent years in patient characteristics and treatment procedures. METHODS: Using data from BRENDA, an unselected cohort with universal coverage of a constant catchment area over a 13-year observation period, this study provides an overview of key trends. RESULTS: Beside steady increases in overall and disease-free survival, main trends in recent years included a gradual increase in new patients' average ages. Grading, but not T stages, improved. Node negative, endocrine responsive patient shares increased; node positive, endocrine responsive shares decreased. HER2neu screening went from uncommon to ubiquitous. Sentinel node biopsy reduced excised numbers of lymph nodes. Second and third generation chemotherapies replaced CMF. Neoadjuvant therapy was gradually introduced. Aromatase inhibitors pushed down Tamoxifen use. 90 % of endocrine responsive patients now receive endocrine therapy. Our results suggest that improved survival only partially results from improved prognostic factors, but rather seems mainly due to improved treatment modalities. CONCLUSIONS: Treatment procedures have changed dramatically over recent years. This was associated with steady increases in favorable outcomes among patients.

Participation in adjuvant clinical breast cancer trials: does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9,433 patients.

UNLABELLED: Adjuvant clinical trials (CTs) usually compare a standard treatment regime versus an innovative new substance or regimen. Participation in CT however, is available for only few patients and exclusion criteria are usually very strict. Therefore we used an unselected patient cohort to investigate the following questions: MATERIAL AND METHODS: This German retrospective multi-centre cohort study included 9433 patients with primary breast cancer recruited from 1992 to 2008. RESULTS: One thousand two hundred and fifty-five (13.3%) patients participated in adjuvant clinical trials (PA) and 8178 (86.7%) did not (NPA). RFS was higher among participants (PA) than among non-participants (NPA) [p=0.006], but differences in overall survival (OAS) were not significant [p=0.15]. When stratified for guideline adherence, the outcome was not different for guideline conform NPA [RFS: p=0.88] [OAS: p=0.37] compared to PA. Survival parameters however, were significantly poorer in non-guideline conform PA [RFS: p<0.001] [OAS: p<0.001] and non-guideline conform NPA [RFS: p<0.001] [OAS: p<0.001] as compared to guideline adherent PA. DISCUSSION: There is a strong association between guideline adherence in adjuvant treatment in BC and survival. PA in clinical trials tended to higher survival rates, but only if guideline-adherent treatment was applied. Patients who do not have access to clinical trials may profit substantially from guideline-adherent adjuvant treatment.

A comparison of international breast cancer guidelines - do the national guidelines differ in treatment recommendations?

AIM OF THE STUDY: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS: We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS: Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT: Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle.

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15-1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03-1.65)). In hormone-receptor-negative (HR-) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80-1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24-2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82-2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63-2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29-1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.

Triple-negative breast cancer: the impact of guideline-adherent adjuvant treatment on survival--a retrospective multi-centre cohort study.

Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.