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Study question Does cryopreservation and transplantation of bovine ovarian medulla-containing cortex tissue improve the viability and vascularization of the graft? Summary answer: Transplantation of bovine ovarian cortex containing medulla has a positive effect on follicular viability and neovascularization of the graft compared to cortex transplantation alone. What is known already For female fertility protection, cryopreservation and retransplantation of ovarian tissue is a widely used method. During cryopreservation, ovarian tissue is exposed to mechanical and hypoxic stress resulting in follicular loss. Moreover, after retransplantation tissue vitality and follicle survival is limited due to ischemia. As follicular viability is of major importance for fertility and hormonal activity, the main focus is on improving vitality and viability of the grafts. In current protocols, ovarian medulla is discarded and merely cortex tissue is preserved. However, medulla tissue predominantly contains blood vessels, thereby obtaining high potential for revascularization processes and thereby supporting tissue vitality. Study design, size, duration This experimental laboratory work was performed during a period of ten months. The rapidly vascularized chorioallantoic-membrane (CAM) of fertilized chicken eggs was used as model system to investigate neovascularization, follicle survival and tissue vitality of different bovine ovarian grafts. In four independent experimental rows four different tissue types (isolated cortex, thick medulla-containing cortex (8 x 10 x 3 mm), thin medulla-containing cortex (5 x 10 x 3 mm) and sole medulla tissue were compared. Participants/materials, setting, methods Out of four bovine ovaries preserved from the slaughterhouse, in total 117 samples of the four different tissue types were primed and cryopreserved by the common slow-freezing protocol. After thawing, grafts were transplanted on separate CAMs at day four of fertilized eggs. After four days of incubation, blood vessels growing towards the grafts were counted. Subsequently, grafts were harvested, digested with collagenase and stained with Neutral Red® to determine the total amount of vital follicles. Main results and the role of chance To investigate the neovascularization, all graft-supplying blood vessels were determined and distinguished between small and thick vessels. Compared to sole cortex, there were more small vessels in the medulla-containing grafts (9,72 vs. 8,65). Especially thin medulla- containing cortex pieces exhibited the highest number of small vessels (9,90). Also in isolated medulla tissue an increased amount of small vessels was observed (9,79). However, the average number of big vessels was not significantly different in all four test groups (Cortex: 2,12; thin medulla-containing cortex: 1,69; thick medulla-containing cortex: 1,5; medulla: 2). The total number of all vessels differed from 10,76 (sole cortex) to 11,75 (medulla-containing grafts), indicating a support of neoangiogenesis by medulla tissue. To further examine whether medulla tissue also alters the amount of vital follicles, Neutral Red® stained vital follicles were determined in all different sample groups. Indeed, in medulla-containing cortex samples was an augmented average number of vital follicles (342,4) compared to sole cortex tissue (256,11). Most vital follicles were detectable in the thick medulla-containing cortex tissue (346,61), closely followed by the thin medulla-containing cortex grafts (338,19). As expected, there was just a rare amount of vital follicles in sole medulla grafts (8,13). Limitations, reasons for caution As the ovarian reserve in cattle is very individual, the prepared ovaries are different in their follicle amount. These individual differences may influence the number of counted follicles. Furthermore, the CAM model is only a short term experimental approach to investigate neovascularization and follicle survival. Wider implications of the findings: According to our results, transplantation of human medulla-containing cortex appears promising. Keeping medulla tissue on the graft seems to improve both follicle viability and revascularization. Our findings need to be proven with human tissue, but might change the preparation of human ovarian tissue for fertility preservation in future. Trial registration number Not applicable

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.

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.

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.

The term 'extreme' whole-body hyperthermia (WBH) describes the procedure of raising a patients' body-core temperature to 41.5-42.0 degrees C for 60 min. WBH represents the only hyperthermia technique that enables systemic heat treatment in patients with disseminated malignancies and is, therefore, usually combined with systemic chemotherapy. Up to now, several WBH-approaches have proved to be safe and associated with acceptable toxicity rates when radiant heat devices are employed. Until the late 1990s, the use of radiant WBH was restricted to a few specialized treatment centres worldwide. During the last 5 years, a larger number of WBH-devices were put into operation particularly in Germany. As a result, a novel generation on phase II trials on chemotherapy and adjunctive WBH in patients with various malignancies has been completed. Based on the promising results observed herein, first multi-centric phase III-trials on chemotherapy +/- WBH have been initiated, with a considerable number of patients treated at German institutions. The authors are members of the 'Interdisciplinary Working Group for Hyperthermia' ('Interdisziplinäre Arbeitsgruppe Hyperthermie'), a sub-group of the German Cancer Society. They formulated these guidelines in order to standardize the WBH treatment procedure and supportive measures, to provide some uniformity in the selection of patients to be treated and to define criteria of a successful WBH-treatment. These recommendations may be helpful to ensure the quality of WBH performed at different institutions.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

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: (1)Are there differences in survival dependent on chemotherapy regimens in stratified by number of positive lymph nodes/grading (G)/hormone receptor-status (HR)/T-stage? (2)Is it possible to attribute these effects to chemotherapy by only investigating patients who received 100% guideline-conform surgery, radiotherapy and endocrine therapy? 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.

Background The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline–taxane–based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. Patients and methods Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, β = 0.8) 379 events had to be observed in the bevacizumab arms. Results With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1–3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. Conclusions Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline–taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. Clinical trial number NCT 00567554, www.clinicaltrials.gov .

UNLABELLED A randomized, double-blind, placebo-controlled, phase 3 trial comparing SMS 201-995 pa LAR plus tamoxifen versus tamoxifen plus placebo in women with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS Numerous studies have proved the efficacy of tamoxifen treatment in women with receptor-positive breast cancer. Preclinical and phase I/II-studies showed that tumor control can be improved if Octreotid is added. In this randomized controlled double blind phase III study women received 20 mg tamoxifen daily and either 160 mg Octreoid-Depot i. m. injection once a month or a placebo injection. Until 1998 a total of 263 women were randomized. RESULTS The study medication was tolerated well by all patients in the treatment group (n = 133). The most frequent moderate side effects were diarrhea (n = 73), nausea (n = 26), abdominal pain (n = 19), bone pain (n = 24) and fatigue (n = 20). No patient dropped out because of these side effects. Surprisingly, several complete remissions occured. Neither the total survival nor the progression free survival was significantly different between groups. Therefore the study was stopped before the originally planned number of patients (n = 416) had been enrolled. CONCLUSION Octreotid plus tamoxifen does not improve tumor control. It is necessary to define subgroups that might benefit from Octreotid.

Fragestellung: Die Tumordokumentation ist fur Qualitatssicherung onkologischer Behandlungen sowie als Quelle zuverlassiger Information uber die sektorubergreifende Versorgung essentiell. Am Beispiel der Mammakarzinomerkrankung wird untersucht, welcher Dokumentationsaufwand und damit verbundener Ressourcenverbrauch besteht. Material und Methoden: Die Versorgungskette bei Patientinnen mit primarem Mammakarzinom in standardisierter Erkrankungssituation wurde von initialer Diagnostik bis Abschluss der Nachsorge definiert. Nach Pilotphase erfolgte mit Unterstutzung des Bundesgesundheitsministeriums eine multizentrische Validierung (n=7 Zentren). Die Dokumentationszeitpunkte wurden horizontal erhoben und mit Lange und Personalaufwand erfasst. Ergebnisse: Das arztliche Personal hat einen Anteil von 57 % der Dokumentationskosten. Je nach Klinik bzw. Zentrum entstehen Kosten von 352,82 bis 1 084,08 € fur den Gesamtablauf der Behandlung von Erstdiagnose bis Abschluss der Nachsorge. In nicht-zertifizierten Zentren zeigt sich ein reduzierter Aufwand und somit geringere Kosten. Schlussfolgerungen: Die Ergebnisse zeigen die Notwendigkeit der Reduktion des Dokumentationsaufwandes – insbesondere fur die arztliche Profession, die kostenintensivste Berufsgruppe im Gesundheitswesen. Da von einer Qualitatsverbesserung durch die Zertifizierung mit ihren speziellen Anforderungen auszugehen ist, ergibt sich die Forderung nach einer adaquaten Vergutung fur die Dokumentation. Des Weiteren ist es erforderlich eine reduzierte Anzahl an Variablen fur die Qualitatssicherung zentral festzulegen und eine flachendeckende berufsubergreifende Dokumentation zu erreichen. Investitionen in einen einheitlichen Datensatz und in Schnittstellenoptimierungen der vorhandenen Dokumentationssysteme sollten erfolgen.

„Schon wieder Myome?“ – werden Sie sich vielleicht gefragt haben, als Sie dieses Themenheft zur Hand genommen haben. Ja, schon wieder. Denn Uterusmyome gehoren zur frauenarztlichen Tatigkeit, wie der Umgang mit Hormonen, Schwangerschaft und Malignomen. Aufgrund ihrer Haufigkeit und der Komplexitat im therapeutischen Umgang fordern sie uns regelmasig heraus: F Myome sind die haufigsten soliden Tumore des weiblichen Genitaltraktes. F Zwischen 20 und 40% der Frauen im reproduktiven Alter entwickeln Myome . F In Europa haben etwa 24 Mio. Frauen Myome. F 20−30% der Hysterektomien erfolgen zur Behandlung von Myomen. F Eine aktuelle amerikanische Studie geht von direkten Gesundheitskosten (Chirurgie, stationare Krankenhausaufenthalte, Arzneimittel) von 4−9 Mrd. US-Dollar jahrlich aus.

154 Background: An earlier published series of neoadjuvant radio-chemotherapy (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. 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—a 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 2 months) increases the probability of a pCR after NRT-CHX.

TPS1146 Background: HER2 status may change over the course of disease in breast cancer pts. Approx. 20-30% of pts with initially HER2-negative breast cancer have HER2-positive metastasis (Zidan et al. 2005; Tewes et al. 2009). Determining HER2 status on CTC is one option to re-evaluate HER2 status at the time metastasis is diagnosed. Currently it is unclear if HER2-targeted therapy based on the assessment of HER2 status of CTC reveals a clinical benefit. Methods: This is a randomized, open-label, two arm phase III study to investigate the clinical efficacy of lapatinib, as a HER2-targeted therapy in initially HER2-negative metastatic breast cancer pts with HER2-positive CTC at the time of distant disease. As only half of the pts with HER2-negative metastatic breast cancer show CTC-positivity and of those approx. 32% will exhibit HER2-positive CTC (Fehm et al. 2010), screening of about 1420 pts is required to enroll 228 pts. Main inclusion criteria: metastatic breast cancer with HER2-negative primary tumor tissue and/or biopsies from metastatic sites or locoregional recurrences, evidence of ≥1 HER2-positive CTC and ≥1 measurable metastatic lesion according to RECIST. Eligible pts will be randomized 1:1 to receive standard treatment vs. standard treatment plus lapatinib. Standard chemo- or endocrine therapy must be approved in combination with lapatinib or been investigated in prior clinical trials. Primary endpoint is progression free survival. Secondary endpoints include overall response rate, clinical benefit rate, overall survival and dynamic of CTC. The DETECT III trial is one of the first trials where treatment is based on phenotypic characteristics of CTC. If this trial succeeds in proving efficacy of lapatinib in pts with initially HER2-negative metastatic breast cancer but HER2-positive CTC, this will establish a new strategy in the treatment of metastatic breast cancer.

e11556 Background: In contrast to neoadjuvant chemotherapy they are no predictive factors to estimate the pathologic complete remission (pCR) rate after preoperative chemotherapy (NRT-CHX) in locally advanced breast cancer (LABC). Methods: 315 LABC patients were included in this trial. They were treated during 1991-1998. The last follow up was in November 2011. Radiotherapy was applied with 50 Gy (5x2 Gy / week) to the breast and the supra-/infraclavicular lymph nodes. 101 patients received a 10 Gy interstitial boost (breast conservation). Chemotherapy (CMF, EC or Mitoxantron was applied in 192 patients prior to radiotherapy and in 113 patients simultaneously. Ten patients had no chemotherapy. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time period up to surgery were examined in multivariate terms for pCR and overall survival. Results: The pCR rate for NRT-CHX after surgery was 29.2%. In multivariante analysis a longer time interval to surgery increased the probability of a pCR (HR 1,17 [95% CI 1,05-1,31], p 2 months) increases the probability of a pCR after NRT-CHX. Like in neoadjuvant CHX the achievement of a pCR is an important prognostic factor for long term survival.

5097 Background: Micro RNAs (miRNAs) are small non-coding RNAs which plays an important role in tumorigenesis and mutation of a miRNA gene or miRNA regulation-related gene may cause butterfly effect on alteration of global gene expression.In order to investigate this hypothesis,high resolution melting analysis (HRM) and denaturing high-performance liquid chromatography (DHPLC) were used to screen 20 miRNA genes and 6 miRNA regulation-related genes for mutations in gynecologic cancers. Methods: In this study,182 DNA samples from breast cancer tumors,42 from ovrian cancers and 28 from endometrial cancers were obtained.18 human cancer cell lines were also included.We used HRM and/or DHPLC to screen mutations of these genes in human cancer cell lines and tumor tissues. All samples with curves that differed in shape compared to wild-type were directly sequenced for confirmation.Secondary structures for the wild-type and variant primary precursor of miRNA sequences obtained from sequencing were predicted using RNAfold software.Western blot and immunohistochemistry were used to evaluate the related protein change in cancer cell line and tumor tissues. Results: Polymorphisms of these genes were very frequently observed in gynecologic cancers.Two rare variants were found in the primary precursor sequences of mir-200c and mir-142 gene.Moreover,a novel frameshift mutation( c.3547_3548insA) in TNRC6A gene was found in two endometrial cacner cell lines (RL95-2 and Hec-1A) and endometrial cancers (1/28).Western blot and immunohistochemistry showed loss of expression of TNRC6A protein in the endometrial cacner cell lines and endometrial cancers with this mutation. Conclusions: Two rare novel variants in 20 miRNA genes and a novel frameshift mutation in TNRC6A gene were identified in gynecologic cancers.Oue data indicate that mutations in TNRC6A gene may contribute to the cancer development and might be a potential new therapeutic target in endometrial cacner.

1020 Background: The prevalence of obesity increases throughout most industrialized countries. Epidemiological studies have shown not only an increase in breast cancer (BC) among obese women but al...

10626 Background: While evidence for the prognostic value of circulating tumor cells (CTC) in the adjuvant setting is swiftly increasing the role of tumor markers like CA27.29 in this setting is still controversial. In the SUCCESS Trial CTC and CA27.29 have been measured before, after and 2 years after adjuvant chemotherapy. Our goal was to examine the correlation of these 2 factors at the 3 points in time. Methods: The SUCCESS Trial compared FEC-docetaxel (Doc) vs. FEC-Doc-gemcitabine (Doc-G) regime and 2 vs. 5 year treatment with zoledronat in 3754 patients with primary breast cancer (N+ or high risk). CA27.29 has been measured with ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Belgium). The cutoff for positivity of CA27.29 was >31 U/ml. CTC were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish between epithelial cells and le...

Methods: A retrospective study was performed of all pregnancies diagnosed with an oligoor anhydramnios and associated renal anomalies during the period 2000–2008. Outcome included mortality and morbidity. Morbidity included renal function; glomerular filtration rate (GFR) at one year. Results: The total group encompassed 71 fetus; 40 fetus with renal dysplasia, 12 fetus with polycystic kidney disease, 19 fetus with obstructive uropathy. Associated anomalies were found in 25/71 (35%) foetus. In 48 patients, renal oligohydramnios was diagnosed before 24 weeks of gestational age (GA); in 41/48 patients the pregnancy was terminated. Twenty-five neonates were born: 10 survived, 15 died of pulmonary hypoplasia. Prognostic factors for survival included GA at diagnosis (32.1 weeks for survivors versus 27.3 weeks for non-survivors; P = 0.02), diagnosis of obstructive uropathy (7 in the survivors versus 4 in the non-survivors: P = 0.05), isolated anomaly (9 in the survivors versus 7 in the non-survivors: P = 0.04) and the severity of the oligohydramnios (1 had anhydramnios in the survivors versus 7 in the non-survivors: P = 0.08). In 80% of the survivors (n = 8) the one-year GFR could be determined: 80% (n = 6) had chronic renal insufficiency. Conclusion: The prognosis of early onset renal oligohydramnios is poor. Determinants for predicting survival included: GA at diagnosis, severity of the oligohydramnios, the diagnosis (obstructive versus non-obstructive renal anomalies) and the presence of associated anomalies.

Effects of G-CSF on circulating tumor cells (CTC) and CA 27.29 in breast cancer patients Andergassen Ulrich 1, Rack Brigitte 1, Schneider Achim 2, Rezai Mahdi 3, Tesch Hans 4, Beck Thomas 5, Soling Ulrike 6, Beckmann Mathias W. 7, Lichtenegger Werner 8, Janni Wolfgang 9 All the following institutions are located in Germany: 1 Ludwig-Maximilians University of Munich; 2 Charite Berlin; 3 Luisenkrankenhaus Dusseldorf; 4 Praxis Prof. Dr. Tesch Frankfurt am Main; 5 Klinikum Rosenheim; 6 Praxis Dr. Soling Kassel; 7 Friedrich-Alexander University of Erlangen; 8 Charite Berlin; 9 Heinrich Heine University of Dusseldorf

551 Background: In several randomized trials, taxane-containing regimens have demonstrated superiority compared to mere anthracycline-containing schedules for the adjuvant treatment of patients wit...