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Purpose The COVID-19 vaccination is probably the most important source to fight the COVID-19 pandemic. However, recommendations and possibilities for vaccination for pregnant and breastfeeding women are inconsistent and dynamically changing. Methods An anonymous, online, cross-sectional survey was conducted among pregnant and breastfeeding women in Germany between 30th March and 19th April 2021 addressing COVID-19 vaccination attitudes including the underlying reasons for their decision. Additionally, anxiety regarding a SARS-CoV-2 infection and a symptomatic course of the infection were evaluated. Results In total, 2339 women (n = 1043 pregnant and n = 1296 breastfeeding) completed the survey. During pregnancy the majority (57.4%) are not in favour of receiving the vaccine, 28.8% are unsure and only 13.8% would get vaccinated at the time of the survey. In contrast, 47.2% would be in favour to receive the vaccine, if more scientific evidence on the safety of the vaccination during pregnancy would be available. Breastfeeding women show higher vaccination willingness (39.5% are in favour, 28.1% are unsure and 32.5% not in favour). The willingness to be vaccinated is significantly related to the women’s anxiety levels of getting infected and to develop disease symptoms. Main reasons for vaccination hesitancy are the women’s perception of limited vaccination-specific information, limited scientific evidence on vaccination safety and the fear to harm the fetus or infant. Conclusions The results provide important implications for obstetrical care during the pandemic as well as for official recommendations und information strategies regarding the COVID-19 vaccination.

PURPOSE: The aim of the present study was to compare birth expectations and antenatal bonding of women pregnant prior to and during the COVID-19 pandemic. MATERIALS AND METHODS: In total, 74 pregnant women (mean age: 33.9 ± 4.1 years, gestational age: 36 ± 2 weeks) participated in the study, who were pregnant either during the the COVID-19 pandemic (corona group, N = 35, April-July 2020) or before the pandemic (control group, N = 39, October 2017-January 2019). Birth expectations were measured using the Wijma Delivery Expectancy Questionnaire (WDEQ) and Salmon's Item List (SIL) and antenatal bonding with the Maternal Antenatal Attachment Scale (MAAS). Additionally, the corona group indicated their level of worry regarding different pandemic-related aspects using visual analogue scales. RESULTS: The corona group displayed significantly elevated fear of childbirth measured by the WDEQ and lower antenatal bonding quality compared to the control group. The additional items regarding COVID-19 burdens highlighted that the aspects that the partner may not be present during labour and that no visitors will be allowed in hospital were associated with the highest worries. CONCLUSIONS: Midwives and gynaecologists should be aware of the negative impact of the COVID-19 pandemic on fear of childbirth and antenatal bonding .

Purpose Stress and impaired mother–infant bonding during pregnancy can lead to adverse effects for the expectant mother and the unborn child. The present study investigates whether a prenatal music and singing intervention can improve maternal well-being as well as mother–infant bonding. Methods A total of 172 pregnant women took part in this prospective, randomised, three-armed (music, singing or control group) study. Depressive symptoms, self-efficacy, maternal well-being and mother–infant bonding were assessed with visual analogue scales and questionnaires before the intervention phase (30th week of gestation) and afterwards (36th week of gestation). Additionally, immediate changes regarding experienced stress and mood from before until after the music and singing interventions were explored with questionnaires as well as saliva samples (for cortisol, alpha-amylase and oxytocin determination). Results Regarding immediate effects, both interventions showed positive effects on the emotional state, stress (cortisol) and bonding (oxytocin). Additionally, the singing group showed a larger reduction in cortisol and a larger improvement in valence than the music group. Looking at more prolonged effects, significant effects on general self-efficacy and perceived closeness to the unborn child (measured with a visual analogue scale) were found. No significant effects were revealed for the mother–infant bonding questionnaire and for depressive symptoms. Conclusion In the present study, promising effects of music and in particular singing on maternal well-being and perceived closeness during pregnancy appeared. Prenatal music and singing interventions could be an easy to implement and effective addition to improve mood and well-being of the expectant mother and support mother-infant bonding. Trial registration number DRKS00012822, date of registration: 17.10.2017

The caesarean section is one of the most frequently performed surgeries. Due to growing economic challenges, hospitals are encouraged to improve their cost-efficiency. One factor that influences hospital costs of caesarean sections is a prolonged hospital stay.The aim of the current prospective study was to investigate psychosocial factors, with an emphasis on anxiety, and sociodemographic factors that are associated with longer hospital stay after caesarean sections with no medical complications. Data of 195 women who gave birth by caesarean section was analyzed. As possible predictors anxiety levels measured pre-, peri- and postoperative as well as age, parity (primiparous/multiparous), repeated caesarean (yes/no), BMI (30/ ≥30), STAI-Trait scores, duration of surgery, PH arterial and Apgar 5 min. were entered into a backward linear regression with duration of hospital stay as the dependent factor.The analysis revealed that higher age, primiparity as well as higher anxiety scores during the postoperative phase are significant factors associated with prolonged hospital stay. The significant model explains 22.1 % of the variance.The results should sensitize the medical team to these risk factors in order to improve patients' recovery and shorten hospital stays.

Around 30% of births are through caesarean section and repetition rates for receiving a caesarean section are high.The aim of the prospective study was to compare the course of anxiety in women undergoing their first caesarean section and women experiencing a repeated caesarean section.304 women with an indication for an elective caesarean section took part. 155 received their first caesarean section and 149 received a repeated caesarean section.In order to measure the course of anxiety on the day of the caesarean section subjective anxiety levels were measured and saliva samples for cortisol determination were taken at admission, during skin closure and two hours after the surgery. Blood pressure and heart rate were documented at skin incision and skin closure.Women experiencing their first caesarean section displayed significantly higher anxiety levels compared to women with a repeated caesarean section. Scores of the STAI-State and visual analogue scale for anxiety differed significantly at admission (p=.006 and p.001) and heart rate and alpha amylase levels were significantly higher at skin closure (p=.027 and p=.029).The results show that previous experience with a caesarean section has a soothing effect. The study aims to sensitize surgeons, anesthetists, nurses and midwives when treating women receiving a caesarean section and encourage them to incorporate soothing interventions, especially for women receiving their first caesarean section to reduce anxiety levels and consequently improve postoperative recovery and patients' satisfaction.

In developed countries, around 25% of all births involve labour induction. Studies have indicated that labour induction negatively influences the birth experience as well as the birth process. However, the impact of labour induction when only considering vaginal deliveries has not been studied yet, which was the purpose of the present study. 186 women who gave birth vaginally took part in this prospective study. 95 women gave birth after spontaneous onset of labour (SL-group) and 91 women received a labour induction (LI-group). Eight to 72 h after birth, the women filled in the revised version of the standardised Childbirth Experience Questionnaire, which examines the birth experience in four dimensions (Own Capacity, Perceived Safety, Participation and Professional Support). Medical details regarding birth and fetal outcomes were taken from the medical records. Birth outcomes (the number of epidural anaesthesia, the duration of birth, birth risks and childbirth injuries) as well as fetal outcomes (APGAR after 1 and 5 min and arterial cord pH) did not differ between the groups. Regarding the subjective birth experience, the LI-group indicated significantly lower values for Perceived Safety and Participation compared to the SL-group, while there were no differences for the dimensions Own Capacity and Professional Support. Successful labour induction resulting in a vaginal birth did not negatively influence birth and fetal outcomes and only partly affected the women’s birth experience. The negative impact of labour induction on the dimensions Perceived Safety and Participation should sensitize midwives in order to provide optimal support.

Background Despite suitable analgesia procedures and interventions only approximately 24% of inpatients with strong to very strong pain receive adequate treatment. Besides opioids, which are associated with numerous side effects and risks, non-pharmacological approaches are increasingly being used. In this context, one of the oldest known methods are music interventions; however, the state of evidence is heterogeneous and there are no explicit manuals and recommendations for the effective implementation of music interventions. Objective This review aimed to determine the optimal time point at which perioperative music interventions can most effectively relieve pain. Material and methods A PubMed search was conducted and publications investigating the effect of music during the preoperative, intraoperative and postoperative stages of various interventions were identified. Results During the preoperative phase, only positive effects of music on pain relief have been reported but availability of data is sparse. During the intraoperative stage of a medical intervention the effect of music seems to be mediated by the type of anesthesia procedure and sedation depth. Only patients who can consciously perceive the music seem to profit from it. Positive alleviating effects on subjective pain perception and analgesia needs were shown in the postoperative stage. Conclusion Music is a non-pharmacological method to alleviate pain, which is free of side effects. Important considerations for the use of music interventions for relief of acute pain associated with surgery are discussed taking into account numerous mediating factors, which influence the efficacy of the treatment.

A positive birth experience for the mother is an important goal in obstetric health care and is influenced by several factors. For this study, 186 women filled in questionnaires between 24 and 72 hours after giving birth vaginally. We evaluated the Big-Five personality traits (extraversion, neuroticism, openness, conscientiousness and agreeableness), trait anxiety, different dimensions of childbirth experience and pain management. Correlation analysis revealed that trait anxiety and neuroticism were negatively associated with several dimensions of the birth experience. Furthermore, conscientiousness and extraversion were positively correlated with the dimension Participation. Regression analysis for the individual dimensions and overall score respectively, confirmed the independent impact of anxiety trait on Perceived Safety, Participation and Professional Support and the overall score as well as of neuroticism on Perceived Safety and conscientiousness on Participation. The significant regression models showed small R2-scores (.084-.154). The birth experience did not differ whether the women received an epidural or not. Women who did not receive an epidural displayed higher scores on the personality trait conscientiousness. The study highlights small but important associations between personality traits and birth experience in vaginal births which should sensitize the medical staff when supporting women during labor.

ObjectiveThere is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.MethodsThe SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24–40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.PerspectiveThis study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.

In recent years, the effect of music interventions and music therapy has experienced increased attention in the literature. It has been shown that music has positive effects on cognitive and physical performance, such as concentration and endurance, as well as on psychological parameters, such as anxiety and relaxation. Studies within the context of medicine in particular are increasingly indicating that music may be used as an intervention for relief against anxiety, stress and pain. Music is therefore seen in actual practice as a supplement to conventional pharmacological and non-pharmacological forms of treatment - and the trend is rising. Studies involving music interventions in the field of obstetrics have shown, amongst other things, that music improves the ability to relax during pregnancy and can reduce anxiety. It was also discovered that during childbirth music interventions resulted in a reduction of pain and stress. Music also has the effect of reducing stress, pain and anxiety in expectant mothers during deliveries by caesarean section. This review intends to provide an overview of the literature on music interventions in the field of obstetrics and to give a resume on the current state of research around the topic of music in relation to pregnancy, spontaneous deliveries and caesarean sections. Furthermore, the relevance of music for everyday obstetrics will be illustrated.In den letzten Jahren wurde die Wirkung von Musikinterventionen und Musiktherapie in der Literatur vermehrt dargestellt. Dabei konnten positive Effekte der Musik auf kognitive und körperliche Leistungen, wie Konzentration oder Ausdauer, sowie auf psychologische Parameter, wie Angst oder Entspannung, gezeigt werden. Vor allem im medizinischen Kontext weisen Studien zunehmend darauf hin, dass Musik als angst-, stress- und schmerzlindernde Intervention eingesetzt werden kann. Daher wird Musik in der Praxis mit steigender Tendenz als Zusatz zu herkömmlichen pharmakologischen und nicht pharmakologischen Behandlungen gesehen. Bei Untersuchungen von Musikinterventionen im Bereich der Geburtshilfe zeigte sich unter anderem, dass Musik während der Schwangerschaft die Entspannungsfähigkeit verbessert sowie Ängste vermindern kann. Auch während der Geburt konnte festgestellt werden, dass Musikinterventionen eine Schmerz- und Stressreduktion zur Folge haben. Bei Geburten durch eine Sectio caesarea wirkt sich Musik ebenfalls stress-, schmerz- und angstreduzierend auf die werdenden Mütter aus. Dieses Review soll einen Überblick über die Literatur der musiktherapeutischen Interventionen im Bereich der Geburtshilfe geben und den aktuellen Forschungsstand zum Thema Musik in Bezug auf Schwangerschaft, spontane Geburten sowie Sectio caesarea zusammenfassen. Des Weiteren wird die Relevanz von Musik für den geburtshilflichen Alltag aufgezeigt.

In order to better understand stress responses, neuroimaging studies have investigated the underlying neural correlates of stress. Amongst other brain regions, they highlight the involvement of the prefrontal cortex. The aim of the present study was to explore haemodynamic changes in the prefrontal cortex during the Maastricht Acute Stress Test (MAST) using mobile functional Near-Infrared Spectroscopy (fNIRS), examining the stress response in an ecological environment. The MAST includes a challenging mental arithmic task and a physically stressful ice-water task. In a between-subject design, participants either performed the MAST or a non-stress control condition. FNIRS data were recorded throughout the test. Additionally, subjective stress ratings, heart rate and salivary cortisol were evaluated, confirming a successful stress induction. The fNIRS data indicated significantly increased neural activity of brain regions of the dorsolateral prefrontal cortex (dlPFC) and the orbitofrontal cortex (OFC) in response to the MAST, compared to the control condition. Furthermore, the mental arithmetic task indicated an increase in neural activity in brain regions of the dlPFC and OFC; whereas the physically stressful hand immersion task indicated a lateral decrease of neural activity in the left dlPFC. The study highlights the potential use of mobile fNIRS in clinical and applied (stress) research.

Background Stress and anxiety during pregnancy and childbirth have negative consequences for both mother and child. There are indications that music has a positive effect in this situation. The present study investigates the influence of music during the caesarean on anxiety and stress of the expectant mother. Methods The SAMBA study is a single-centre, controlled, randomized study including 304 patients. Women in the intervention group heard music via loudspeakers from one of four self-selected genres. The control group had standard treatment without music. The caesarean was performed in regional Anesthesia. At admission, at skin incision, during skin suture and two hours after completion of surgery, different subjective (State-Trait Anxiety Inventory, visual analogue scale for anxiety) and objective parameters (salivary cortisol/amylase, heart rate, blood pressure) were collected. Mixed-factorial Analysis of variances as well as independent sample t-tests were applied for data analysis. Results At skin suture, significantly lower anxiety levels were reported in the intervention group regarding State anxiety (31.56 vs. 34.41; p = .004) and visual analogue scale for anxiety (1.27 vs. 1.76; p = .018). Two hours after surgery, the measured visual analogue scale for anxiety score in the intervention group was still significantly lower (0.69 vs. 1.04; p = .018). The objective parameters showed significant differences between the groups in salivary cortisol increase from admission to skin suture (12.29 vs. 16.61 nmol/L; p = .043), as well as systolic blood pressure (130.11 vs. 136.19 mmHg; p = .002) and heart rate (88.40 vs. 92.57/min; p = .049) at skin incision. Conclusions Music during caesarean is an easy implementable and effective way of reducing stress and anxiety of the expectant mother. Trial registration German registry for clinical trials (DRKS00007840). Registered 16/06/2015. Retrospectively registered.

Background: Evidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up. Patients and Methods: The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs. FEC followed by docetaxel plus gemcitabine, and 2 vs. 5 years of treatment with zoledronic acid in 3,754 patients with node-positive or high-risk node-negative early-stage breast cancer. CA27.29 was measured with the ST AIA-PACK CA27.29 reagent (Tosoh Bioscience, Belgium). The cutoff for CA27.29 positivity was >31 U/ml. CTCs were assessed with the CellSearch System (Veridex, USA). The cutoff for CTC positivity was >= 1 CTC/15 ml whole blood. The relationship between CTC positivity and CA27.29 positivity was assessed based on Chi-square statistics and Cramer's V, which varies from 0 (no association between the variables) to 1 (complete association). Samples for CA27.29 and CTC determinations during follow-up were only drawn from patients that had no relapse. Results: Both CA27.29 and CTC data were available for 1,981, 1,602, 1,159 and 707 patients before, immediately after and at 2 and 5 years after CHT, respectively. Positivity rates for CTC were 21.3%, 22.8%, 18.6% and 8.5%, respectively. CA27.29 was positive in 7.9%, 21.0%, 2.8% and 7.5%, respectively. Positivity for both CA27.29 and CTC was found in 2.4%, 4.2%, 0.7% and 1.8% of patients, respectively. The association between CA27.29 and CTC was significant but weak before CHT (p=0.0015;Cramer's V=0.063) and 5 years after CHT (p

D The present study examined the association between granulocyte colony-stimulating factor (G-CSF) and prognostic markers cancer antigen (CA)27.29 and circulating tumor cells (CTCs) in 2646 early-stage breast cancer patients. Those with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy than those without any G-CSF application during chemotherapy, although no association with CTCs was found. Background: Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA) 27.29 and circulating tumor cell (CTC) levels during therapy. Patients and Methods: A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy. Results: Overall, 1324 of the 2646 patients (50.0%) available for analysis had >= 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (chi(2) = 30.6, df = 3;P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test;Z - -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (chi(2) = 1.2, df = 3;P = .75). Conclusion: Cautious interpretation is needed regarding elevated levels of MUC-1 - derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy.

Uterus myomatosus und Endometriose gehoren zu den haufigsten benignen, gynakologischen Erkrankungen der Frau. Beide sind heutzutage eine Domane der laparoskopischen Therapie. Der aktuelle Stellenwert der fertilitatserhaltenden minimal-invasiven Chirurgie zur Behandlung von Uterus myomatosus und Endometriose wird anhand der verfugbaren Evidenz aufgezeigt. Mithilfe einer Pubmed-Suche wurde die aktuelle Literatur auf Relevanz gepruft, ebenso wurden die einschlagigen Leitlinien der Fachgesellschaften konsultiert. Die Laparoskopie konnte die Therapie dieser Erkrankungen sowohl in Hinsicht auf die Symptomkontrolle als auch auf die Fertilitat weiter verbessern. Durch die flachendeckende Einfuhrung laparoskopischer Behandlungsansatze in der Myom- und Endometriosetherapie kann einer Vielzahl von Patientinnen, die einen oft langen Leidensweg hinter sich haben, nicht nur effizient, sondern auch schonend und nicht zuletzt mit dem optimalen kosmetischen Ergebnis geholfen werden.

Background: Recent trials have provided evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients (pts). The SUCCESS C study is the first randomized Phase III trial to evaluate the effect of an intensive lifestyle intervention program, focusing on both physical activity and healthy diet following adjuvant chemotherapy on disease-free survival in women with early breast cancer. Methods: SUCCESS C is a German multicenter, 2×2 factorial design, randomized phase III study comparing disease-free survival (DFS) in pts with HER2-negative early breast cancer treated with either 3 cycles of epirubicine, fluorouracil, cyclophosphamide chemotherapy followed by 3 cycles of docetaxel (FEC-D) or 6 cycles of docetaxel-cyclophosphamide (DC). The second randomization compares DFS in pts with a body mass index (BMI) of 24—40 kg/m2 receiving either a telephone-based individualized lifestyle intervention (LI) program aiming at moderate weight loss for 2 years (LI arm) or general recommendations for a healthy lifestyle alone (non-LI arm). DFS according to lifestyle intervention was analyzed using both univariable cox regressions and multivariable cox regressions adjusted for age (years, continuous), BMI (kg/m2, continuous), menopausal status (premenopausal, postmenopausal), tumor size (pT1, pT2, pT3/pT4), nodal stage (pN0, pN1, pN2, pN3), hormone receptor status (positive, negative), grading (G1, G2, G3), histological type (ductal, lobular, other) and chemotherapy randomization (FEC-D, DC). Median follow-up was 64.2 months. Results: Overall, 2292 of the 3643 pts recruited for the SUCCESS C study were randomized for the lifestyle intervention program (1146 pts in both the non-LI arm and the LI arm). The Intention-to-treat analysis revealed no difference in DFS between the two treatment arms (LI vs. non-LI) in univariable analysis (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.76 — 1.28, p = 0.922) and in adjusted multivariable cox regression (HR 0.91, 95% CI 0.70 — 1.18, p = 0.48). At the 2-year follow up, pts in the LI arm lost on average 1.0 kg weight compared to the start of the LI program, while pts in the non-LI arm gained on average 0.95 kg (p < 0.001). Overall, 1477 pts completed the 2-year LI program (non-LI arm: 80.7%, 925 of 1146 pts; LI arm: 48.2%, 552 of 1146 pts; p < 0.001). Pts that completed the 2-year LI program had a significant better DFS than non-completers (HR 0.35, 95% CI 0.27 — 0.45, p < 0.001). Among completers, pts in the LI arm had a significantly better DFS than pts in the non-LI arm both in univariable analysis (HR 0.53, 95% CI 0.35 — 0.82, p = 0.004) and in adjusted multivariable cox regression (HR 0.51, 95% CI 0.33 — 0.78, p = 0.002). Conclusions: This explorative and non-planned interim analysis indicates that the completion of a systematic telephone life style intervention program may positively impact patient outcome in early breast cancer. Citation Format: Janni W, Rack BK, Friedl TW, Müller V, Lorenz R, Rezai M, Tesch H, Heinrich G, Andergassen U, Harbeck N, Schochter F, De Gregorio A, Tzschaschel M, Huober J, Hepp P, Fehm TN, Schneeweiss A, Lichtenegger W, Blohmer J, Hauner D, Beckmann MW, Häberle L, Fasching PA, Hauner H. Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-03.

Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and therapy in systemic cancer. However, their infrequent and unreliable detection, especially in nonmetastatic cancer, currently impedes the clinical use of CTCs. Because leukapheresis (LA) targets peripheral blood mononuclear cells, which have a similar density to CTCs, and usually involves processing the whole circulating blood, we tested whether LA could substantially increase CTC detection in operable cancer patients. Therefore, we screened LA products generated from up to 25 L of blood per patient in two independent studies, and found that CTCs can be detected in more than 90% of nonmetastatic breast cancer patients. Interestingly, complete white blood cell sampling enabled determining an upper level for total CTC numbers of about 100,000 cells (median, 7,500 CTCs) per patient and identified a correlation of CTC numbers with anatomic disease spread. We further show that diagnostic leukapheresis can be easily combined with the US Food and Drug Administration-approved CellSearch system for standardized enumeration of CTCs. Direct comparison with 7.5 mL of blood revealed a significantly higher CTC frequency in matched LA samples. Finally, genomic single-cell profiling disclosed highly aberrant CTCs as therapy-escaping variants in breast cancer. In conclusion, LA is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of CTCs as in the sense of a liquid biopsy. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring of early systemic cancer.

Die SUCCESS‑A-Studie ist eine prospektive multizentrische Phase-III-Studie beim primaren Mammakarzinom. Verglichen wird die rezidivfreie Uberlebenszeit nach Randomisierung bei Patientinnen nach 5-Fluorouracil-Epirubicin-Cyclophosphamid (FEC), gefolgt von 3 Zyklen Docetaxel (D) vs. 3 Zyklen FEC, gefolgt von 3 Zyklen Gemcitabin-Docetaxel (DG). Nach erneuter Randomisation erfolgt ein Vergleich einer 2-jahrigen vs. 5‑jahrigen Zoledronat-Therapie. 251 Zentren rekrutierten 3754 Patientinnen in einem Zeitraum von 18 Monaten. Die Auswirkungen der Studienteilnahme auf die Behandlungs- und Versorgungssituation sollten durch einen an die Studienzentren versandten Fragebogen erfasst werden. Nach Auswertung der 78 zuruckgesandten Fragebogen zeigte sich, dass 40 % der Zentren ihre Patientinnen zuvor nicht in klinische Studien eingebracht hatten. 4 % verabreichten in einer High-Risk-Situation vor Studienteilnahme CMF- oder ein anderes nicht naher gekennzeichnetes Protokoll. 46 % indizierten eine anthrazyklinbasierte und 50 % eine taxanbasierte Chemotherapie. Die Halfte der Zentren bemerkten eine grosere Betreuungsintensitat und eine Verbesserung der Gesamtqualitat der medizinischen Betreuung – unabhangig von der rein studienbedingten Zuwendung – sowie einen grosen Informationszugewinn durch die Integration in das Studiennetzwerk. Alle Zentren wurden nach den Erfahrungen im Rahmen der SUCCESS-A-Studie wieder an einer klinischen Phase-III-Studie teilnehmen. Diese Daten geben einen Hinweis darauf, dass Patientinnen und Arzte von der Teilnahme an einer Studienteilnahme profitieren, da – unabhangig von der erhofften studienspezifischen Therapieverbesserung – eine bessere Behandlungsqualitat erreicht werden kann.

Die SUCCESS‑A-Studie ist eine prospektive multizentrische Phase-III-Studie beim primaren Mammakarzinom. Verglichen wird die rezidivfreie Uberlebenszeit nach Randomisierung bei Patientinnen nach 5-Fluorouracil-Epirubicin-Cyclophosphamid (FEC), gefolgt von 3 Zyklen Docetaxel (D) vs. 3 Zyklen FEC, gefolgt von 3 Zyklen Gemcitabin-Docetaxel (DG). Nach erneuter Randomisation erfolgt ein Vergleich einer 2-jahrigen vs. 5‑jahrigen Zoledronat-Therapie. 251 Zentren rekrutierten 3754 Patientinnen in einem Zeitraum von 18 Monaten. Die Auswirkungen der Studienteilnahme auf die Behandlungs- und Versorgungssituation sollten durch einen an die Studienzentren versandten Fragebogen erfasst werden. Nach Auswertung der 78 zuruckgesandten Fragebogen zeigte sich, dass 40 % der Zentren ihre Patientinnen zuvor nicht in klinische Studien eingebracht hatten. 4 % verabreichten in einer High-Risk-Situation vor Studienteilnahme CMF- oder ein anderes nicht naher gekennzeichnetes Protokoll. 46 % indizierten eine anthrazyklinbasierte und 50 % eine taxanbasierte Chemotherapie. Die Halfte der Zentren bemerkten eine grosere Betreuungsintensitat und eine Verbesserung der Gesamtqualitat der medizinischen Betreuung – unabhangig von der rein studienbedingten Zuwendung – sowie einen grosen Informationszugewinn durch die Integration in das Studiennetzwerk. Alle Zentren wurden nach den Erfahrungen im Rahmen der SUCCESS-A-Studie wieder an einer klinischen Phase-III-Studie teilnehmen. Diese Daten geben einen Hinweis darauf, dass Patientinnen und Arzte von der Teilnahme an einer Studienteilnahme profitieren, da – unabhangig von der erhofften studienspezifischen Therapieverbesserung – eine bessere Behandlungsqualitat erreicht werden kann.

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: MUC1 based tumor markers like CA27.29 (TM) in breast cancer are routinely used in metastatic disease as early marker for treatment efficacy. However, in early stage disease data is sparse. In this analysis, we looked at the impact of individual change in CA27.29 on prognosis instead of using a threshold. Methods: The SUCCESS Trial compares FEC-docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in 3754 patients (pts) with primary breast cancer (N+ or high risk N0). We measured CA27.29 after surgery but before chemotherapy (CHT) as baseline and compared it to CA27.29 levels 2 years thereafter with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Results: CA27.29 data is available of 2,015 pts. 119 pts (5.9%) had TM over the threshold of 32U/ml before CHT and 56 (2.8%) 2years thereafter. To examine the relative change of tumor marker, pts were divided into 3 groups: increase: change >=5 U/ml; stable: change = −5 U/ml. 123 (6.1%) pts had increasing (>=5 U/ml), 1419 (70.4%) had stable, 473 (23.5%) had decreasing TM levels from before CHT to 2 years thereafter. The majority of pts with increasing TM (86 pts; 69.9%) had levels below the usual threshold of 32U/ml at all times. Patients with an increase >=5 U/ml had an 81% increased risk for recurrence (HR = 1.810 [CI: 1.111–2.948]) and reduced overall survival (HR = 1.020 [CI: 1.004–1.037]). In the multivariate analysis taking into account tumor size, nodal status, grading, age, hormonal and HER2/neu receptor status increasing CA27.29 levels were an independent prognostic marker. Conclusions: An increase of the tumor marker CA27.29 2 years after CHT compared to pre-chemotherapy baseline was associated with a worse prognosis. By using this approach, more patients at risk for recurrence were detected than with the standard threshold approach. Therefore, the use of relative change could help to identify more patients at risk for relapse who might benefit from an intensified follow up. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-25.

Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer.The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility.Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009).The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.Metaanalysen zeigten die Überlegenheit von taxanhaltigen Chemotherapien gegenüber rein anthrazyklinbasierten Therapieregimen bei Hochrisiko-Mammakarzinompatientinnen.Die ADEBAR-Studie, als multizentrische Phase-III-Studie, randomisierte nodalpositive Mammakarzinompatientinnen entweder in den sequentiellen Anthrazyklin-Taxan-Arm oder in den FEC120-Arm. Die Patientinnen erhielten 4× Epirubicin (90 mg/mHämatologische Toxizität fand sich signifikant häufiger im FEC-Arm. Febrile Neutropenie trat bei 11,3% der Patientinnen im FEC-Arm auf sowie bei 8,4% der Patientinnen im EC-Doc-Arm (p = 0,027). Schwere nicht-hämatologische Nebenwirkungen Grad 3/4 traten in beiden Armen selten auf. Aufgrund von Toxizitäten musste die Therapie bei 3,7% der Patientinnen im EC-Doc-Arm sowie bei 8,0% der Patientinnen im FEC-Arm abgebrochen werden (p = 0,0009).Das sequentielle Anthrazyklin-Taxan-Regime ist eine gut verträgliche Alternative zu FEC120.

Background Disseminated tumor cells (DTCs) in bone marrow and circulating tumor cells (CTCs) in blood are found in patients with epithelial carcinomas (breast cancer) and are often correlated with poor prognosis of the disease. In current models circulating tumor cells (CTCs) dissolved from the primary tumor are thought to be responsible for the occurrence of metastases. However, the detection of CTCs is still a technical challenge. In this study, two methods for tumor cell detection of patients’ samples are presented (Real-Time-PCR and immunohisto-chemical staining). Both are simple and known methods with a high sensitivity and a spread marker panel. Materials and Methods For the implementation of both methods, different breast cancer cell lines have been used (Cama-1, MCF-7; ZR-75-1). For Real-Time-PCR, blood samples of a healthy donors were spiked with different cell counts (0, 10, 100, 1000, 10.000 and 100.000) per ml blood sample. Total RNA was isolated from the samples, reversely transcribed into cDNA and used for TaqMan Real-Time-PCR reaction with probes against CK8, 18 and 19, while 18S was used as reference. Relative Quantification Curves were drawn by Microsoft™ Excel®. For immunohistochemical staining, cytospins were prepared from spiked blood samples, fixed with acetone, air dried and stained with antibodies against Her2- and Thomsen-Friedenreich-Antigen (CD176). In a second staining step fluorescently labelled secondary antibodies were applied. Nuclei were counterstained with DAPI, TF-Antigen was stained by Cy2 and Her2-Antigen by Cy3. The staining was controlled and documented by an epifluorescence microscope. Results The curve of Relative Quantification for MCF-7 and ZR-75-1 cells shows an increasing slope starting from 1000 cells. For the Cama-1 cell line this trend is already seen from 10–100 cells. In ZR-75-1 all three genes analysed reveal this trend, whereas in Cama-1 and MCF-7 cells a strong increase in Relative Quantification is especially seen for CK8 and 18. In the immunohistochemical staining, the cells were considered as tumour cells if they showed staining with the antibody-combinations used. Stained cells were counted and recovery rates were determined. For ZR-75-1, 17 of 30 cells which were spiked in the blood samples were recovered. For MCF-7, 18 cells were found in average, and for Cama-1 23 cells were located per slide. The recovery rates calculated from these numbers are 56,6% and 60,0% for ZR-75-1 and MCF-7, for Cama-1 the recovery rate reaches 76,6%. Conclusion It seems that Cama-1 cells are a better model than MCF-7 and ZR-75-1 for Real-Time PCR quantification of mamma carcinoma tumor cells in blood samples. MCF-7 and ZR-75-1 cells tend to react more likely immunologically with blood cells of the donor (agglutination between blood cells and cancer cells). The Cama-1 cell line shows also advantages in the detection of tumor cells using immunohistochemical staining. Therefore it will be necessary to test both methods on patient samples to proof their benefit. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-24.

Background: The prognostic significance of CTC in metastatic, as well as in primary breast cancer has been demonstrated (Rack et al., ASCO 2010). The optimal endocrine treatment strategy for postmenopausal patients (pts) with hormone sensitive breast cancer remains unclear.We analyzed the prevalence of CTC two years after primary diagnosis in patients with tamoxifen or anastrozole treatment. Methods: As part of the translational research project of the German SUCCESS-trial, we analyzed 23ml of peripheral blood from 307 N+ and high risk N-postmenopausal pts with hormone sensitive breast cancer two years after adjuvant taxane based chemotherapy and with tamoxifen or anastrozole treatment. The presence of CTCs was assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish between epithelial cells and leukocytes. Standard within the study was early switch treatment (tamoxifen for 2 years, followed by anastrozle), while pts with contraindications against tamoxifen were allowed to receive anastrozole up-front. Results: In 10.1% of pts (n=31) >1 CTC was detected after the completion of chemotherapy (range 2-33), while 7.8% (n=24) presented with >1 CTC (range 2-99) two years after completion of chemotherapy. The median age in the tamoxifen group was 59.9 years and 59.8 in the anastrozole group. In the tamoxifen group, 33.0% of the pts had a pT1 tumor, 5.3% G1 grading and 21.6% of the pts were node negative. In the anastrozole group, 30.0% of the pts had a pT1 tumor, 7.5% G1 grading and 22.5% of the pts were node negative, respectively. None of these differences were statistically significant. After the completion of chemotherapy, 9.7% of the pts were CTC positive in the tamoxifen group (range number of cells: 2-33) and 11.3% in the anastrozole group (range of cells: 2-24), p=0.69. Two years after primary diagnosis, 7.9% of the pts were CTC positive in the tamoxifen group (range number of cells:2-99) and 7.5% in the anastrozole group (range cells: 2-5), p=0.90. Actuarial disease free and overall survival will be presented at the meeting. Conclusions: The prognostic relevance of CTC in peripheral blood of early breast cancer patients both before and after chemotherapy has been demonstrated. The presented data will add information on the monitoring potential of CTC during adjuvant endocrine treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-08.

Adjuvant therapy with the third-generation aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane has largely replaced the use of tamoxifen (TAM) as standard adjuvant endocrine treatment for postmenopausal women with hormone-sensitive early breast cancer. Treatment strategies investigated in large, randomized, well-controlled clinical studies include the use of an AI as an upfront replacement for TAM, as an alternative to continued treatment with TAM, and in the extended adjuvant setting after at least 5 years of TAM. The efficacy of AIs over TAM has been demonstrated, particularly in terms of improving disease-free survival (DFS), and reductions in early distant metastasis with AIs may ultimately translate into improved overall survival. As AI therapy offers prolonged DFS, safety is an important concern over the long term. The AIs are better tolerated than TAM in terms of troublesome gynecologic adverse events such as vaginal bleeding and discharge, as well as life-threatening complications such as venous thromboembolic events and endometrial cancer. On the other hand, AI therapy has been associated with losses in bone density and a potential effect on lipids and cardiovascular risk. In trials comparing AIs with TAM, only limited conclusions can be made because of the putative cardioprotective, lipid-lowering, and bone-sparing effects of TAM. Studies comparing AIs with placebo, and/or in healthy women, may be more useful in understanding the long-term safety of adjuvant AI therapy. Results of ongoing safety analyses within some of the large AI trials should provide further insight into the long-term tolerability of AI therapy in the adjuvant setting.

Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.

Background: Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer. Methods: CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0–54). Kaplan–Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided. Results: Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) Conclusions: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.

Ein Workshop zu Operationstechniken bei Patientinnen mit Endometriose fand am 29. 11. 2014 in Berlin statt. Im Folgenden geben Renner et al. einen Uberblick uber den Workshop.

Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications.Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores.We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period.LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.

Minimal residual disease (MRD), i.e., isolated tumor cells (ITC) in bone marrow, may be the source of potentially fatal overt distant metastases in solid tumors even years after primary treatment. MRD can be detected by immunohistochemical methods using antibodies directed against cytokeratins, cell-surface markers, or molecular PCR-based techniques. Among solid tumors, the clinical relevance of MRD has been most extensively studied in breast cancer patients. The highest level of evidence for the prognostic impact of MRD in primary breast cancer was reached by a pooled analysis comprising more than 4,000 patients, showing poor outcome in patients with MRD at primary therapy. Yet, clinical application of MRD detection is hampered by the lack of a standardized detection assay. Moreover, clinical trial results demonstrating the benefit of a therapeutic interference derived from bone marrow status are still missing. Recent results suggest that in addition to its prognostic impact, MRD can be used for therapy monitoring or as a potential therapeutic target after phenotyping of the tumor cells. Persisting MRD after primary treatment may lead to an indication for extended adjuvant therapy. In a pooled analysis bone marrow aspirates of 726 patients from academic breast cancer units in Oslo (n=356), Munich (n=228), and Tuebingen (n=142) were analyzed during recurrence-free follow-up at a mean interval of 31.7 months after primary diagnosis of breast cancer pT1-4, pN0-3 pM0. Persistent ITC was detected in 15.4% of the patients (n=112). The Kaplan–Meier estimate for mean distant relapse-free survival estimate was 163.6 months in patients with negative and 105.2 months in patients with positive BM status. Patients without evidence of persistent ITC had a significantly longer overall survival (165.6), than patients with positive bone marrow status (103.3 months, p < .0001). Given these inspiring results on ITC in the bone marrow, several trials currently analyze the prognostic relecance of circulating tumor cells (CTC) in peripheral blood in the adjuvant setting. Persisting MRD after primary treatment may lead to an indication for extended adjuvant therapy. However, until clinical consequences of MRD detection in solid tumors and particularly in breast cancer have been validated, the detection of isolated tumor cells in bone marrow should be performed mainly in clinical trials.