Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study

Background: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients. Methods: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor–positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT. Results: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment. Conclusions: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process. Trial registration Clinical Trials Number: CFEM345DDE1

Diagnostische und klinische Wertigkeit der Dopplersonographie der beiden Arteriae uterinae in einem "low-risk"-Kollektiv zwischen der 21. und 24. Schwangerschaftswoche

0. Title page and contents 1. Introduction 1 2. Patients and methods 5 2.1. Patients 5 2.2. Method of examination 10 2.3. Evalution 12 3. Results  16 4. Discussion  55 4.1. Definition of "risk pregnancies" 55 4.2. Problems of evaluation 56 4.2.1. Time of assessment 56 4.2.2. Definition and registration of outcome variables 57 4.2.2.1. Preeclampsia 57 4.2.2.2. Placental abruption 61 4.2.2.3. Intrauterine growth retardation 61 4.2.2.4.  Preterm delivery 62 4.2.2.5. Perinatal mortality 63 4.2.3. Therapeutic interventions 64 4.2.4. Definition of abnormal waveform 66 5. Summary and conclusions  68 6. References 71 Curriculum vitae 81 Acknowledgements 84Objective: To identify the definition of pathological waveform which optimises the diagnostic value of Doppler sonography of the uterine arteries (DSUA) at 20-23 gestational weeks as a screening procedure in a low risk population Patients and methods: In a prospective study, 7502 singleton pregnancies with well known outcome were evaluated. Outcome variables included preeclampsia, intrauterine growth retardation, placental abruption, intrauterine / early neonatal death and preterm delivery before 28 respectively 32 completed gestational weeks. Results: Best performance was reached by the use of a combination of impedance and presence of notch (no notch and mean PI>P95 or unilateral notch and mean PI>P90 or bilateral notch and mean PI>P50). With this method, the sensitivity for preeclampsia was 54.91% with a specificity of 93.4%, the sensitivity for placental abruption was 42.3% with a specificity of 93.2%, the sensitivity for preterm delivery <32 completed gestational weeks was 41.5% with a specificity of 93.5%, the sensitivity for delivery of an SGA-fetus was 31.2% with a specificity of 94.0%. Uni- or bilateral notching alone, elevated impedance alone and another combination of notching and elevated impedance (no notch and mean PI>P90, unilateral notch and mean PI>P50 or bilateral notch in combination with any impedance) performed worse. Conclusion: Best results of DSUA are reached using an appropriate definition of pathological waveform which combines presence of notch and elevated impedance. Preconditions are adequate time of assessment and adequate definition of outcome variables. Our data support the hypothesis that under these circumstances, DSUA as primary screening test even in a "low-risk obstetric population" seems to be a useful tool to identify a relevant part of those women who are at elevated risk for some of the major pregnancy complications.Ziel: Klaerung der diagnostischen Wertigkeit verschiedener Definitionen eines pathologischen Flussmusters der Arteriae uterinae bei klar definierter Schwangerschaftsphase unter vollstaendiger Erfassung der vorhersagbaren Schwangerschaftskomplikationen. Patientinnen und Methodik: In einem "low risk" Kollektiv untersuchten wir prospektiv 7502 Patientinnen, von denen uns nach Durchführung der Dopplersonographie der Arteriae uterinae das outcome der Schwangerschaft bekannt war. Die Untersuchungen fanden zwischen der 21. und 24. Schwangerschaftswoche statt. Die beruecksichtigten Zielgroeßen waren Prae- Eklampsie, intrauterine Wachstums-retardierung, vorzeitige Plazentaloesung, perinatale Mortalitaet sowie die Fruehgeburt vor Ende der 32. Schwangerschaftswoche. Ergebnisse: Wir verglichen 4 verschiedene Definitionen von pathologischem Flussmuster. Die beste diagnostische Aussage erreichten wir mit der Kombination des Widerstandes (PI) und dem Auftreten eines Notch (kein Notch und mean PI>P95, unilateraler Notch und mean PI>P90, bilateraler Notch und mean PI>P50).Mit dieser Kombination fanden wir eine Sensitivitaet fuer Prae- Eklampsie von 54.9% mit einer Spezifitaet von 93.4%, eine Sensitivitaet fuer vorzeitige Plazentaloesung von 42.3% mit einer Spezifitaet von 93.2%, eine Sensitivitaet fuer Fruehgeburt vor Ende der 32. Schwangerschaftswoche von 41.5% mit einer Spezifitaet von 93.5%, sowie eine Sensitivitaet fuer intrauterine Wachstumsretardierung von 31.2% mit einer Spezifitaet von 94.0%. Andere Definitionen eines pathologischen Flussmusters erbrachten schlechtere Ergebnisse. Diskussion: Voraussetzungen fuer eine rationelle Anwendung der Dopplersonographie der Arteriae uterinae sind die Durchfuehrung zu einem vernuenftigen Zeitpunkt, eine vernuenftige Definition der Zielgroessen sowie optimale Definition eines pathologischen Flussmusters. Unter diesen Vorraussetzungen sind in einem "low risk" Kollektiv Entdeckungsraten von ueber 30% schwerer pathologischer Schwangerschaftsverlaeufe, mit einer falsch positiven Rate von unter 8% erreichbar

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

Background: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. (C) 2016 S. Karger GmbH, Freibur

Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

Background. Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods. The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Results. Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly (P 65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. Conclusions. This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor