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In den letzten Jahrzehnten sind zwar Fortschritte in der Behandlung des metastasierten Mammakarzinoms erzielt worden, jedoch orientieren sich nur wenige Therapien an den individuellen Eigenschaften der Patientin oder der Tumorerkrankung. Mehr als 10 Jahre nach der Veroffentlichung der menschlichen genetischen Sequenz haben sich die Analysemethoden dahingehend verbessert, dass grose Hoffnung besteht, die Therapie weiterzuentwickeln und im Sinne einer „Prazisionsmedizin“ individuell fur die Patientin und die Tumorerkrankung zu gestalten. Hierbei werden Biomarker auf jeder Ebene der Systembiologie herangezogen (Genetik, Epigenetik, Genexpression, micro-RNA, Proteomics und weitere). Diese Individualisierung hat zu einer neuen Generation von Studien gefuhrt, sodass manche Arzneimittelentwicklungen nur noch fur sehr kleine Patientinnen-Subgruppen durchgefuhrt werden. Die Organisation der Erfassung von Patientinnen und molekularen Tumordaten ist deswegen von besonderer Bedeutung fur die erfolgreiche Durchfuhrung von klinischen Studien. Diese neue Form der Medizin stellt eine besondere Herausforderung fur Patientinnen und Arzte dar. Der Erhalt der Lebensqualitat sollte auch in diesem neuen Zeitalter der Medizin als zentrales Therapieziel im Fokus stehen. In diesem Ubersichtsartikel werden wir die Entwicklungen der letzten Jahre aufzeigen und das PRAEGNANT-Studiennetzwerk vorstellen, welches die oben genannten Probleme und Ziele angeht und eine professionalisierte Infrastruktur hierfur aufbaut.

Einleitung: Die EvaluateTM-Studie (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor positive breast cancer patients receiving letrozole treatment) ist eine prospektive, nicht interventionelle Studie, die das Therapiemanagement und die Compliance im Rahmen der Routineversorgung unter einer Therapie mit Letrozol bei postmenopausalen Patientinnen mit einem invasiven, hormonrezeptorpositiven Mammakarzinom als Studienziel hatte. In dieser Publikation werden die Parameter bei Studieneinschluss berichtet. Material und Methoden: Von Januar 2008 bis Dezember 2009 wurden insges. 5045 Patientinnen in 310 Prufzentren in die EvaluateTM-Studie eingeschlossen. Zugelassen waren Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom in der adjuvanten und metastasierten Therapiesituation. 373 Patientinnen mussten aus unterschiedlichen Grunden aus den Analysen ausgeschlossen werden. Ergebnisse: Insgesamt wurden 4420 Patientinnen in der adjuvanten und 252 Patientinnen in der palliativen (metastasierten) Situation in die Studie eingeschlossen. Bei 4181 Patientinnen in der adjuvanten Situation wurde direkt nach operativer Therapie mit einer Aromataseinhibitortherapie mit Letrozol begonnen (upfront). Bei 200 Patientinnen wurde zunachst Tamoxifen gegeben und in den Jahren 2 – 5 nach Diagnosestellung mit der Aromatasehemmertherapie mit Letrozol begonnen (switch), und bei 39 Patientinnen erst 6 – 10 Jahren nach Diagnosestellung (extended endocrine therapy). Die Patientinnen- und Tumorcharakteristika lagen ebenso wie die Begleiterkrankungen und die Begleitmedikation im Bereich des Erwarteten. Schlussfolgerung: Die Daten der EvaluateTM-Studie werden einen guten Einblick in das Therapiemanagement von postmenopausalen Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom im Rahmen der Routineversorgung geben. Geplante Analysen beinhalten die Therapiepersistenz und die Zufriedenheit mit den Informationsstrukturen und dem Aufklarungsinhalt.

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.

Standard der postoperativen Strahlentherapie des brusterhaltend operierten Mammakarzinoms ist die Bestrahlung der gesamten Restbrust mit einer anschliesenden Aufsattigung des Tumorbetts (sog. „boost“). Aufgrund der haufigeren Diagnose kleinerer Mammakarzinome bei postmenopausalen Patientinnen durch das Mammographie-Screening ergibt sich die Notwendigkeit, uber mogliche Veranderungen der bisherigen Therapiealgorithmen nachzudenken. Der Grosteil der Lokalrezidive tritt im Bereich der ehemaligen Tumorhohle auf. Infolgedessen wird aktuell diskutiert, ob eine alleinige Bestrahlung des Tumorbetts die Radiotherapie der gesamten Restbrust ersetzen kann.

Das Skelettsystem ist als Metastasierungsort beim fortgeschrittenen Mammakarzinom am haufigsten betroffen. Die wichtigsten physiologischen Aufgaben des Knochens sind seine Stutzfunktion und die Kalziumspeicherung. Am Knochenstoffwechsel sind vornehmlich zwei Zellpopulationen mit gegenlaufiger Funktion beteiligt, Osteoblasten und Osteoklasten. Wird deren Gleichgewicht gestort, beispielsweise durch die Invasion von Tumorzellen und Freisetzung osteolytischer Faktoren, kommt es in einer Art Circulus vitiosus zur Destruktion des Knochens. Daraus ergeben sich die unter dem Begriff „skeletal related events“ (SRE) zusammengefassten Komplikationen. Zur Diagnostik von Knochenmetastasen stehen neben der Anamnese verschiedene Verfahren der Bildgebung zur Verfugung (Skelettszintigraphie, Rontgen, Computer- und Magnetresonanztomographie). Die Therapie ist interdisziplinar zu entscheiden, sie richtet sich vor allem nach dem Benefit fur die Patientin. Im Vordergrund stehen dabei Schmerzreduktion und Funktionserhalt. Neben der Radiatio und der operativen Intervention zur lokalen Metastasenkontrolle sind Systemtherapien mit Bisphosphonaten oder einem RANKL-Inhibitor indiziert.

Background: Breast cancer patients make frequent use of complementary and alternative medicine (CAM), but few prospectively collected data are available specifically for postmenopausal breast cancer patients receiving adjuvant antihormonal therapy. The aim of the study was to identify the characteristics of patients who are interested in integrative medicine (IM). Methods: The EvAluate-TM study is a prospective noninterventional study, in which treatment with letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. 5,045 patients were enrolled at 339 certified breast centers. As part of the data collection process, patients were asked at the baseline about their interest in and information needs about IM. Results: 3,411 patients responded to the questionnaire on IM and took part in the analysis. 1,583 patients expressed an interest in IM. Relevant predictors of interest in IM were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in IM declined highly significantly (P < 0.001) with age. In addition, these women were mostly interested in receiving information about their disease from a physician. Conclusions: This study shows that postmenopausal women have a strong interest in IM. Information about IM should therefore be included in patient care for this patient group. Especially the patients receiving concomitant medication, which is one of the main predictors for women not being interested in IM, may need special attention. In addition, most patients were interested in obtaining the relevant information from their doctor, indicating that responsibility for this lies with the treating physicians.

Tumour documentation is essential for quality assurance of oncological therapies and as a source of reliable information about the in- and outpatient care. The documentation effort and the associated resource consumption were analysed for the example of breast cancer.The different steps in the care of patients with primary breast cancer in a standardised disease situation were defined from initial diagnosis to the end of the follow-up. After the pilot phase, a multicentre validation (n=7 centres) was performed with the support of the Federal Ministry of Health. The documentation time points were horizontally collected and analysed with regard to amount, duration and personnel expenses.57% of the documentation costs are caused by the physicians. Regarding the different centres, documentation costs were calculated between € 352.82 and € 1 084.08 per patient from diagnosis to completion of aftercare. Non-certified centres had a reduced documentation effort and thus lower costs.The results demonstrate the need for a reduction of the documentation effort - particularly for physicians - the most expensive profession in the health system. A quality improvement is expected from the certification with its special requirements. In this context, there is a justified demand for an adequate remuneration of the documentation effort for certified centres. Furthermore, it is necessary to reduce the number of variables for quality assurance and to define them centrally. A comprehensive multi-disciplinary documentation should be achieved. Investments in a single data set and interface enhancements of existing documentation systems should be realised.

Fragestellung: Patienten mit fruhem oder metastasierten Mammakarzinom bei denen im peripheren Blut zirkulierende Tumorzellen (CTCs) nachgewiesen wurden, haben eine schlechtere Prognose. Werden nach einer (neo-)adjuvanten Chemotherapie CTCs gefunden, konnten sie moglicherweise von einer zusatzlichen systemischen Therapie profitieren (Rack 2014). Neue Daten bestarken die Hypothese, dass Trastuzumab Tumorzellen auch durch eine Antikorper-vermittelte Immunreaktion eliminiert und dass der therapeutische Nutzen mit einer Wirkung auf Tumorstammzellen in Zusammenhang stehet (Ithimaki 2013). Unabhangig vom HER2 Status der CTCs oder des Primartumors, konnte Trastuzumab in einer Pilotstudie CTCs eliminieren und die Rezidivrate senken (Georgoulias 2012). Methodik: TREAT CTC ist eine europaweite randomisierte Phase-II-Studie unter der Sponsorschaft der EORTC und der Schirmherrschaft der BIG. Es wird die Effektivitat von Trastuzumab bei der Elemination von CTCs nach (neo-) adjuvanter Chemotherapie und Operation beim HER2-negabitebn fruhen Mammakarzinom gepruft. Haupteinschlusskriterien: Eingeschossene Patienten werden zu entweder 6 Zyklen Trastuzumab alle 3 Woche oder zur Beobachtung randomisiert. Anschliesend wird erneut die CTC-Last im periphereren Blut bestimmt. Europaweit sollen in 100 Zentren 2175 Patienten gescreent werden, um 174 Studienteilnehmer zu randomisieren. Ergebnisse: Bis heute konnten in Deutschland 394 Patienten gescreent und 15 Patienten randomisiert werden. Schlussfolgerung: TREAT CTC ist die erste randomisierte Multizenter-Studie, die CTCs zur Therapieentscheidung beim fruhen Mammakarzinom nutzt Angesichts der prognostischen Relevanz von CTCs wird diese Studie dazu beitragen, den klinischen Nutzen des Nachweises von CTCs in diesem Setting zu prufen.

Purpose: The WSG BCIST study was designed to assess the influence of Prosigna results, on physicians’ adjuvant treatment recommendations by determining the extent of change in pre-test treatment recommendations following assay results. Secondary objectives were to assess the influence of Prosigna results on physicians’ confidence in their therapeutic recommendations and on patients’ decisional conflict status, anxiety levels, and functional status. Methods: This prospective, observational, decision impact study enrolled consecutive postmenopausal patients with ER-positive, HER2-negative, lymph-node negative early-stage breast cancer in 11 centers in Germany. Physicians based their pre-test adjuvant treatment recommendations on standard clinico-pathological parameters. Tumor specimens were assayed using the Prosigna test in the WSG central pathology laboratory following manufacturer’s guidelines. An independent pathology laboratory performed subsequent Prosigna assays on tumor sections to assess assay results concordance with the central laboratory. Physicians completed treatment confidence questionnaires prior to and after receiving Prosigna test results. Patients completed standardized questionnaires on decisional conflict, anxiety, and health status both before and after Prosigna testing. Results: The present study population consisted predominantly of low-to-intermediate risk patients (N=198). Prosigna had 29.3% discordance in intrinsic subtyping with local immunohistochemistry test results. After Prosigna test results, a change in the adjuvant therapy recommendation occurred in 36 (18.2%) patients; 22 (11.1%) patients switched from no chemotherapy to chemotherapy. After Prosigna results, physicians expressed increased confidence in their prognostic assessment in 87.9% of patients, and increased confidence in their treatment recommendation in 89.4%. Patients reported improved anxiety and emotional/functional well-being after receiving Prosigna results. Conclusions: Use of the Prosigna assay led to a change in 18.2% of adjuvant treatment decisions. Prosigna testing was associated with increased patient and physician confidence in treatment decisions, and with decreased patient anxiety and improved well-being. Any comparison of the therapeutic decision-making impacts of different genomic assays must account for potential confounding factors.

Background: In younger patients (pts) breast cancer (BC) is associated with a worse prognosis compared to older pts. Only few data are available presenting the development of prognostic factors regarding a period of several decades. This 40 year (y) longitudinal comparison of the main prognostic factors was performed to investigate differences in younger women with primary BC in contrast to older women over time. Patients and Methods: In this retrospective analysis a consecutive pts cohort of 4010 pts was analyzed. Pts were documented and treated for primary invasive breast cancer between 1963 and 2003 at two University Hospitals in Germany. To be eligible, pts were required to have identified tumor characteristics, including TNM-status. Pts with carcinoma in situ or distant metastases were excluded. The cohort was divided in two age groups, ≤40y and >40y. Furthermore to reveal trends and changes over the duration of 41 years the period of analysis was split into 3 time frames: 1963–1976, 1977–1989 and 1990–2003. We analyzed the main prognostic factors for BC including tumor size, grading, nodal status and HR-status in longitudinal comparison regarding the three time frames, respectively. During 1963–77 HR-status was determined in just 12.6% of pts. Thus, this time frame was excluded in the analysis of HR-status. Results: In 41 yrs, 747 (18.6%) pts were treated between 1963–76, 1722 pts (42.9%) in 1977–89 and 1541 pts (38.4%) in 1990–2003. Overall 358 pts were ≤40y and 3652 pts were over the age of 40. A significant reduction of tumor size (metric assessment) at primary diagnosis was observed for both age groups (pts≤40y: p = 0.012; pts>40y: p < 0.0001) with no difference between the time frames, respectively (1963–76: p = 0.289; 1977–89: p = 0.647; 1990–2003: p = 0.937). The number of node-positive pts significantly decreased in pts >40 y (p = 0.001) whereas no difference could be seen in pts aged ≤40 y (p = 0.991). In both age groups the number of G2/3 tumors increased over the yrs (pts≤40y: p = 0.001; pts>40y: p < 0.0001). Between 1963–76 more G1-tumors were diagnosed in younger pts (p = 0.041) whereas in the two following periods significantly more G2/3 tumors (p = 0.001; p = 0.002) were observed in this group. In young pts, 54.2% were HR-negative in 1977–89 and 47.6% in 1990–2003 (p = 0.323). In pts >40y 38.4% and 21.7% were HR-negative, respectively (p < 0.0001). Comparing the age groups, significantly more pts were HR-negative in the young patient group (p = 0.001 (1977–89) and p < 0.0001 (1990–2003)). Conclusions: Concerning the large period of 40yrs, technical improvement and increasing awareness for BC are reasons for decreasing tumor size at the time of primary diagnosis. However, the rate of node-positive pts in the young patient group remained stable. Furthermore, the high percentage of HR-negative pts and the increasing number of pts with unfavorable tumor grade demonstrate more aggressive tumor types in younger pts. These data confirm the need to improve screening tools to early identify young women with the risk to develop breast cancer, and for personalized treatment approaches in these patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-11.

Background: An earlier published series of neoadjuvant radio-chemotherapy (NRT-CHX) in locally advanced non-inflammatory breast cancer (LABC) has now been updated with a follow up of more than 15 years. Long- term outcome data and predictive factors for pathologic complete response (PCR) were analyzed. Patients and Methods: 315 LABC patients (cT1-cT4/cN0-N1) were treated during 1991–1998 with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or – in case of breast conservation – an 10-Gy interstitial boost with 192Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time interval between end of RT and surgery were examined in multivariate terms with as endpoint pCR and overall survival. Results: The total PCR rate after neoadjuvant RT-CHX reached 29.2 % with LABC breast conservation becoming possible in 50.8%. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1,17 [95% CI 1,05-1,31], p < 0,01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80 to 0.99], p = 0.03) could be obtained. Importantly, a pCR was the strongest prognostic factor for long term survival (HR 0.28 [95% CI 0.19–0.56], p < 0.001). Conclusions: A PCR identifies patients with a significant better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of a pCR after NRT-CHX. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-04.

An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed.During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 ? 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point.The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p 2 months) increases the probability of pCR after NRT-CHX.

Die Inzidenz der gestationsbedingten Trophoblasterkrankungen ist zwar mit 1 pro 100.000 Schwangerschaften gering, doch diese Erkrankungen konnen mit einer relevanten maternalen Morbiditat assoziiert sein. Als sichere Risikofaktoren gelten ein maternales Alter unter dem 20. und uber dem 35. Lebensjahr, eine Blasenmole oder das Auftreten von Aborten in der Anamnese sowie bestimmte Blutgruppenantigenkonstellationen. Wahrend komplette und partielle Blasenmolen lediglich mit dem Risiko einer persitierenden Trophoblasterkrankung assoziiert sind, zeichnen sich die invasive Mole, das Chorionkarzinom und der „placental site trophoplastic tumor“ (PSTT) durch eine gesteigerte Proliferationstendenz aus und konnen in andere Organe metastasieren. Typische klinische Symptome sind Blutungen in der Fruhschwangerschaft, ein vergroserter Uterus und Hyperemesis gravidarum. Diagnostisch wegweisend sind deutlich erhohte HCG-Werte sowie die Ultrasonographie. Ziel der Therapie ist die vollstandige Entleerung des Uterus, ggf. auch eine Hysterektomie bei abgeschlossener Familienplanung. Eine Chemotherapie ist in Abhangigkeit von Risikofaktoren fur eine persistierende Trophoblasterkrankung erforderlich.