The use of axillary ultrasound (AUS) to assess the nodal status after neoadjuvant chemotherapy (NACT) in primary breast cancer patients.

INTRODUCTION: Axillary Ultrasound (AUS) is standard for pre-therapeutic axillary staging in early breast cancer patients. 35-75 % of the breast cancer (BC) patients with positive axillary lymph nodes receiving neoadjuvant chemotherapy (NACT) convert to pathological node negative. For those patients, axillary surgery after NACT could be de-escalated, if an accurate prediction of the pathologic nodal status following NACT was possible. This study aims to answer the question, whether AUS can be used as a reliable diagnostic tool for restaging of axillary nodal status after NACT. PATIENTS AND METHODS: We collected data of 96 patients with nodal positive primary breast cancer who received NACT between 2009 and 2015 at the Breast Cancer Center of the University Hospital Ulm. Patients were classified as node negative or positive by AUS after NACT (ycN + or ycN0) and the results were compared to the pathological result obtained after axillary lymph node dissection (ypN + vs ypN0) in all patients. RESULTS: 58.3 % of the patients had pathological complete remission of axillary lymph nodes after NACT (ypN0). The sensitivity and specificity of AUS were 57.5 % and 78.6 %, respectively. The FNR was 42.5 %. The Positive and Negative Predictive Values (PPV and NPV) were 65.7 % and 72.1 %, respectively. The accuracy of AUS was 69.8 % and not associated with any of the investigated clinico-pathological parameters. CONCLUSION: AUS alone is not accurate enough to replace surgical restaging of the axilla after NACT in initially node positive breast cancer patients.

Psycho-Oncological Care Provision in Highly Distressed Breast Cancer Patients.

Objective To evaluate the proportion of breast cancer (BC) patients with distress or psychological comorbidity as well as offer and use of psychological support in subgroups of BC patients with different extents of distress. Methods 456 patients with BC were evaluated at baseline (t1) and until 5 years after diagnosis (t4) at the BRENDA certified BC centers. Logistic regression was used to analyze if patients with distress at t1 received offers and actual psychological support more often than patients without distress at t1. Regression analyses were used to examine if acute, emerging or chronic disease was associated with higher rates of offer and use of psychotherapy as well as intake of psychotropic drugs. Results In 45% of BC patients psychological affection was detected at t4. The majority of patients with moderate or severe distress at t1 (77%) received the offer for psychological service, while 71% of those received the offer for support at t4. Patients, who were psychologically affected at t1, have not been offered psychological services more often than those without, but they significantly more often used services if offered. Especially patients with acute comorbidity received significantly more often an offer for psychotherapy compared to unimpaired patients, while those patients with emerging or chronic disease did not. 14% of BC patients took psychopharmaceuticals. This mainly concerns patients with chronic comorbidity. Conclusion Psychological services were offered to and used by a fair amount of BC patients. All subgroups of BC patients should be addressed, in order to improve the comprehensive supply with psychological services.

Predictors of Decreased Quality of Life in Breast Cancer Survivors Five Years After Diagnosis.

PURPOSE: Due to improved therapy, early diagnosis, and growing incidence rates, the number of long-term breast cancer survivors is increasing. Survivors can still be affected by aftercare, resulting in reduced quality of life (QoL). Thus, in this study, we investigated possible predictors of decreased physical and social functioning in breast cancer survivors. METHODS: In a German multicenter prospective study, we enrolled 759 female patients with breast cancer before surgery (t1), and contacted them again 5 years after surgery (t4). Data on QoL were assessed at t4 using the European Organization for Research and Treatment of Cancer QoL Core Questionnaire (EORTC QLQ-C30) and its breast cancer module EORTC QLQ-BR23. Predictors of decreased physical and social functioning were analyzed using logistic regression with odds ratios as effect estimates and 95% confidence intervals. Thresholds for the clinical importance of detrimental effects on QoL were defined according to Giesinger. RESULTS: Questionnaires from 759 patients were retrieved at t1. Of these, 456 participated in the study at t4. Poor QoL 5 years after diagnosis was reported by 20%-50% of the participants. Age, mastectomy, chemotherapy, education, employment, cohabitation, psychiatric comorbidities at t1, anxiety, depression, and intensity of physical activity emerged as predictors of decreased physical and social functioning 5 years after diagnosis. CONCLUSION: Relief of symptoms and improvement in the QoL should be priorities in aftercare. Detecting patients with a decreased QoL is a rising challenge. Healthcare providers should take special care of patients aged 50-59 years, patients with psychiatric comorbidities and depression, and patients who have undergone mastectomy.

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.

A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany.

BACKGROUND: Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. METHODS: In a cohort of 11,982 BC patients diagnosed in 1998-2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. RESULTS: Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94-1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98-1.01, P = .68). CONCLUSIONS: Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

Outcome analysis of primary breast cancer patients who declined adjuvant chemotherapy-results from the prospective multi-center BRENDA II study.

BACKGROUND: This study examined 5-year overall, recurrence and distant metastasis-free survival (OS, RFS, MFS) of high- and intermediate-risk breast cancer (BC) patients who declined guideline-recommended adjuvant chemotherapy (CHT). METHODS: In the prospective multicenter cohort study BRENDA II, patients with primary BC were sampled over a period of four years (2009-2012). A multi-professional team (tumorboard) discussed recommendation for adjuvant CHT according to the German guideline. Potential differences in 5 year survival were analyzed using Kaplan-Meier curves and Cox regression. The hazard ratios (HR) were adjusted for age, Charlson Comorbidity Score, American Society of Anesthesiologist (ASA) physical status classification, and endocrine therapy. RESULTS: A total of 759 patients were enrolled of which 688 could receive CHT according to the guidelines (n = 219 had a clear indication, in n = 304 it was possible). For 360 patients, the tumorboard advised to perform CHT, for 304 it advised against and in 24 cases, no decision was documented. Of those with a positive suggestion, 83% received CHT. Until 5 years after diagnosis, 57 patients were deceased, 41 had at least one distant metastasis and 29 a recurrence. There was no evidence for differences in OS and MFS in patients who declined CHT despite tumorboard recommendation (HR 3.5, 95% CI 0.8-15.1 for OS, HR 1.9, 95% 0.6-6.6 for MFS). Patients who received CHT had significantly better 5-year RFS compared to those who declined (HR 0.3, 95% CI 0.1-0.9, p = 0.03). There was no evidence for different survival in those who had no CHT because of comorbidity and those who declined actively, neither for OS, MFS nor RFS. CONCLUSION: The prospective BRENDA II study demonstrates benefit in RFS by guideline adherence in adjuvant breast cancer treatment, indicating prospectively the value of internationally validated guidelines in breast cancer care.

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.

BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients.

Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project [1]. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7-3.3); intermediate risk: HR = 5.0, 95%CI.(3.6-6.9); high risk: HR = 10.3, 95%CI (7.4-14.3) and very high risk: HR = 18.1, 95%CI (13.2-24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.

Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases - a transSENTINA Analysis.

Background Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear. Methods Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Results Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR. Conclusions Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.

Correction: Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases - a transSENTINA Analysis.

[This corrects the article DOI: 10.1055/a-1298-3453.].

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.

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.

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.

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.

Prevalence of Cardiac Disease in Breast Cancer Patients at Time of Diagnosis Compared to the General Female Population in Germany.

BACKGROUND: Advances in oncological therapy have significantly improved breast cancer survival; therefore comorbid conditions are becoming more relevant. We investigated the prevalence of prior cardiovascular diseases and risk factors in patients with breast cancer compared to those in the general female population in Germany. METHODS: The PASSOS heart study is a retrospective multicenter cohort study on cardiac late effects in breast cancer patients treated between 1998 and 2008. We analyzed the frequencies of cardiac diseases and cardiovascular risk factors in patients from this cohort as documented in anesthesia protocols compared to self-reported frequencies in the general female population in Germany. RESULTS: 3,496 patients aged between 40 and 79 years who underwent breast surgery were considered for analysis. The age-standardized prevalence of cardiac diseases or cardiovascular risk factors was 6.75 versus 7.52% and 69 versus 80.92%, respectively. Coronary heart disease (3.96 vs. 5.18%) and angina pectoris (0.37 vs. 1.03%) prevalence was lower in breast cancer patients, while non-fatal myocardial infarction (2.06 vs. 1.81%) and stroke (2.64 vs. 2.34%) were more frequent (not statistically significant). CONCLUSION: Pre-existing cardiac diseases and cardiovascular risk factors are common in both study populations, being slightly less frequent in the PASSOS cohort. When making therapy decisions, the cardiac risk profile should be carefully monitored and taken into account.

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.

Validation of a Nomogram Predicting Non-Sentinel Lymph Node Metastases among Patients with Breast Cancer after Primary Systemic Therapy - a transSENTINA Substudy.

BACKGROUND: Prediction of non-sentinel lymph node (SLN) status after primary systemic therapy (PST) may allow tailored axillary staging. The aim of this analysis was to compare established nomograms from i) the primary operative (n = 6) and ii) the neoadjuvant (n = 1) setting with an optimized nomogram to predict non-SLN status in patients after PST. METHODS: 181 patients converting from cN1 prior to PST to ycN0 but found to have a histologically positive SLN in the SENTINA trial were analyzed. Established models were applied. An optimized model was compiled using univariate and subsequent multivariable logistic regression (backward selection, likelihood ratio test). RESULTS: Area-under-the-curve (AUC) values from the primary operative models showed sufficient performance (0.82-0.71). For the neoadjuvant model, the AUC was found to be inferior to prior analyses (0.66) but within published confidence intervals. The SENTINA nomogram comprised the diameter of the largest lymph node (p = 0.006, odds ratio (OR) = 1.19), tumor size prior to PST (p = 0.085, OR = 1.31), and number of all positive SLN (p = 0.083, OR = 2.04). This model was validated using a separate cohort of arm C (n = 168, AUC 0.79, 95% confidence interval 0.74-0.85). CONCLUSION: We validated 7 models of prediction of non-SLN among patients showing axillary conversion through PST. Our own 'SENTINA nomogram' yielded AUC values comparable to previous nomograms.