COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy.

BACKGROUND: COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. PATIENTS AND METHODS: At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. RESULTS: In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. CONCLUSIONS: While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.

Adhesions and Anti-Adhesion Systems Highlights.

The peritoneal and intrauterine cavities are lined by fragile membranes with a high-wound healing capacity, e.g. repairing the endometrium in its cyclical "injury and scar-free repair process" during menstruation. However, peritoneal and intrauterine fibrosis and adhesions can develop after surgical trauma through activation of molecular, immune and genetic mechanisms. During procedures with a high-risk of adhesions, the use of new peritoneal and intrauterine conditions in combination with anti-adhesion substances are promising measures to preserve peritoneal and endometrial function and avoid the most common complication of gynecological surgery. Highlights of adhesions and anti-adhesion prevention techniques in laparoscopic, laparotomic and hysteroscopic surgeries are discussed in this paper. Unfortunately, evidence is lacking to prove the superiority of one technique over its counterparts in terms of postoperative adhesions, such as instrumentation, type of energy, distending media, and intracavitary pressure. Additionally, there is limited evidence about the efficacy and outcomes of techniques and adjuvant measures used during adhesiolysis. The definition of a universal intrauterine adhesions classification scheme as well as a prognostic scoring system to identify women at high risk of postoperative adhesions are necessary for advising those who could benefit the most of the use of antiadhesion barriers.

Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.

PURPOSE: The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. PATIENTS AND METHODS: This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer. Here, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. At dose levels (DL) I and II, one instance of dose-limiting toxicity (DLT) was seen in one of 6 patients. At DL III, two of four patients showed a DLT, leading to a maximum tolerated dose (MTD) of 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, respectively. 155 adverse events (AE) occurred, most frequently elevation of liver enzymes, leukopenia, diarrhea and fatigue. Altogether, five serious adverse events (SAE) developed in four patients. CONCLUSION: Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.

From Clinical Symptoms to MR Imaging: Diagnostic Steps in Adenomyosis.

Adenomyosis or endometriosis genitalis interna is a frequent benign disease of women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea and seems to have a negative effect on fertility. Adenomyosis can be part of a complex genital and extragenital endometriosis but also can be found as a solitary uterine disease. While peritoneal endometriosis can be easily diagnosed by laparoscopy with subsequent biopsy, the determination of adenomyosis is difficult. In the following literature review, the diagnostic methods clinical history and symptoms, gynecological examination, 2D and 3D transvaginal ultrasound, MRI, hysteroscopy, and laparoscopy will be discussed step by step in order to evaluate their predictive value in the diagnosis of adenomyosis.

Health-related Quality of Life in Metastatic and Adjuvant Breast Cancer Patients.

Introduction: When cancer patients have advanced disease and a primary cure is no longer possible, the focus is on maintaining the patient's quality of life. Recent therapeutic advances in breast cancer treatment mean that even patients with metastatic disease can remain stable for long periods of time. The aim of this study was to look at the health-related quality of life (HRQL) of these patients and compare it with data for the general population and to show the differences in outcomes for different survey instruments used to measure quality of life. Material and Methods: A total of 96 breast cancer patients with metastatic disesae or receiving adjuvant therapy were questioned about their quality of life. Patients were investigated using the established survey instruments EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and EQ VAS. All patients filled out questionnaires. Statistical analysis was done using MS Excel and SPSS. Results: Although the questionnaires were completed at the same time, the different questionnaires showed significant differences with regard to the level of stress experienced by the patient. When the EQ VAS questionnaire was used, the patient's current state of health was assessed as significantly better than with the EORTC QLQ-C30. Overall, all aspects of patients' quality of life were found to be in need of optimization and HRQL of patients was significantly poorer in all areas compared to the reference population. Conclusion: To improve the quality of life of patients with metastatic disease, it is necessary to continuously monitor the success of therapy. The choice of survey tools is highly relevant as assessments differ considerably depending on the choice of questionnaire.

Adjuvant chemotherapy in elderly patients with primary breast cancer: are women ≥65 undertreated?

PURPOSE: To establish whether women over 65 years of age with newly diagnosed with breast cancer (BC) receive adjuvant chemotherapy less frequently than younger postmenopausal women and whether comorbidity influences this potential undertreatment. MATERIALS AND METHODS: In a single-site, retrospective, comparative study, postmenopausal early stage BC patients treated between 01/2001 and 12/2005 at a major German university hospital were analyzed in two age Groups A and B (≥65 vs. <65 years) for initiation and completion of guideline-recommended adjuvant chemotherapy. Risk stratification was based on the 2005 St. Gallen Consensus Conference criteria. Comorbidity was parametrized using the Charlson Comorbidity Index (CCI). RESULTS: Analysis included 634 patients, 380 in Group A and 254 in Group B. Mean age (range) was 73 (65-94) and 61 (55-64) years, respectively. The proportion of patients from Group A given ≥3 cycles of chemotherapy was significantly decreased as compared to Group B. 52 % of patients with CCI <3 but only 20 % with CCI ≥3 were recommended to undergo chemotherapy (p < 0.001). Median follow-up [95 % confidence interval (CI)] was 85 (82-88) months. DFS was significantly shorter in patients aged ≥65 years as compared to younger postmenopausal patients (HR, 0.598; 95 % CI, 0.358-0.963; p = 0.048). CONCLUSIONS: Despite being high-risk patients, older women with early stage BC were often not given guideline-recommended chemotherapy. Higher recurrence rates compared with younger postmenopausal women suggest that older patients are undertreated. Treatment needs to be adapted to general health and tumor biology rather than age. More trials in elderly BC patients are needed.

Willingness of Patients with Breast Cancer in the Adjuvant and Metastatic Setting to Use Electronic Surveys (ePRO) Depends on Sociodemographic Factors, Health-related Quality of Life, Disease Status and Computer Skills.

Introduction: Because of the often unfavorable prognosis, particularly for patients with metastases, health-related quality of life is extremely important for breast cancer patients. In recent years, data on patient-relevant endpoints is being increasingly collected electronically; however, knowledge on the acceptance and practicability of, and barriers to, this form of data collection remains limited. Material and Methods: A questionnaire was completed by 96 patients to determine to what extent existing computer skills, disease status, health-related quality of life and sociodemographic factors affect patients' potential willingness to use electronics methods of data collection (ePRO). Results: 52 of 96 (55 %) patients reported a priori that they could envisage using ePRO. Patients who a priori preferred a paper-based survey (pPRO) tended to be older (ePRO 53 years vs. pPRO 62 years; p = 0.0014) and typically had lower levels of education (p = 0.0002), were in poorer health (p = 0.0327) and had fewer computer skills (p = 0.0003). Conclusion: Barriers to the prospective use of ePRO were identified in older patients and patients with a lower quality of life. Given the appropriate conditions with regard to age, education and current health status, opportunities to participate should be provided to encourage patients' willingness to take part and ensure the validity of survey results. Focusing on ease of use of ePRO applications and making applications more patient-oriented and straightforward appears to be the way forward.

Clinical Characteristics, Surgical Management and Adjuvant Therapy of Patients with Uterine Carcinosarcoma: A Retrospective Case Series.

Purpose: To review a single-center experience over a 27-year period of managing uterine carcinosarcoma (UCS), focusing on surgical practice, adjuvant therapy and clinical outcome. Material and Methods: This was a retrospective study of women with histologically proven UCS treated at the Department of Obstetrics and Gynecology, University of Tübingen, Germany, between 1983 and 2010. Inpatient and outpatient records were reviewed; follow-up and survival data were ascertained. Results: The study population comprised 18 patients with UCS. Primary surgical treatment consisted of total abdominal hysterectomy in 12 patients (67 %) and laparoscopic total hysterectomy in 4 patients (22 %). Bilateral salpingo-oophorectomy was performed in 94 % of patients (17/18). Lymph nodes were evaluated in 15 patients (83 %). Positive pelvic lymph nodes were present in 2 patients (11 %). A total of 17 patients (94 %) received adjuvant therapy. Disease recurred in 7 (39 %) patients of our study group, with no recurrence noted in the 4 patients who underwent laparoscopic surgical staging. Median disease-free survival (DFS) was 48.7 months (95 % CI: 0.0-157.3) and median overall survival (OS) was 49.9 months (95 % CI: 0.0-108.2). The 5-year survival rate was 40 %. Conclusion: UCS is a rare and aggressive uterine neoplasm with high recurrence rates and metastatic potential. Surgical staging consisting of total hysterectomy with bilateral salpingo-oophorectomy and systematic lymphadenectomy is the most important treatment for patients with UCS. Adjuvant radiation therapy appears to decrease pelvic recurrence, but there is a high incidence of distant recurrence, indicating the need for additional systemic treatment.

Adhesions and endometriosis: challenges in subfertility management : (An expert opinion of the ANGEL-The ANti-Adhesions in Gynaecology Expert PaneL-group).

There is molecular evidence that endometriosis has a negative impact on the ovaries, although the exact pathophysiology concerning endometriosis-associated subfertility is not known. The negative impact on the tubo-ovarian unit can be directly by distorting the anatomy, indirectly by invoking inflammation or by oxidative damage with poorer-quality oocytes. Endometriosis even seems to have a negative effect on pregnancy outcome after in vitro fertilization.

Radiofrequency Volumetric Thermal Ablation of Fibroids and Laparoscopic Myomectomy: Long-Term Follow-up From a Randomized Trial.

Aims: Laparoscopic myomectomy (LM) has been the gold standard treatment for uterine fibroids in women desiring uterine conservation. To evaluate a new fibroid treatment modality - radiofrequency volumetric thermal ablation (RFVTA) - we compare 12-month results in women who had symptomatic uterine fibroids and who were randomized to laparoscopic ultrasound-guided RFVTA or LM. Materials and Methods: Our study is a 1 : 1 parallel, randomized, prospective, single-center, longitudinal, comparative analysis of RFVTA to LM for fibroid treatment in women ≥ 18 years of age who desired uterine conservation. Fifty women were randomized intraoperatively to RFVTA (n = 25) or to LM (n = 25) after laparoscopic ultrasound mapping of the uterus. Results: Post surgery, ablation and myomectomy subjects took pain medications for 4 days (range: 1-46) and 7 days (range: 1-83 days) respectively (p = 0.60). Ablation and myomectomy subjects missed 10.0 workdays (range: 2-86 days) and 17.0 workdays (range: 7-30 days) (p = 0.28), resumed normal activities in 20.5 days (range: 5-103 days) versus 28.0 days (range: 10-42 days) (p = 0.86) respectively. Mean symptom severity scores decreased (improved) by - 7.8 for the ablation subjects and by - 17.9 for the myomectomy subjects (p = 0.16). Health-related quality of life improved (increased) by 7.5 and 13.1, respectively, for the two groups (p = 0.46). Two myomectomy subjects had pregnancies that ended in a Cesarean delivery and a vaginal delivery of healthy infants. Two pregnancies in the RFVTA group ended in full-term vaginal deliveries of healthy infants. Conclusions: Early postoperative recovery and twelve-month results attest to similar clinical benefits from RFVTA and LM.

Assessing the need for psychooncological support: screening instruments in combination with patients' subjective evaluation may define psychooncological pathways.

BACKGROUND: Cancer patients suffer from severe distress. About one third show mental comorbidities. Nevertheless, there is no common agreement on how to measure distress or identify patients in need for psychooncological services using screening questionnaires. PATIENTS AND METHODS: A sample of N = 206 patients with confirmed breast cancer, being inpatient for surgical treatment, filled in distress assessment instruments: Distress Thermometer, Hospital Anxiety and Depression Scale, Patient Health Questionnaire 2, Hornheider Screening Instrument and parts of the EORTC-QLQ-C30. Additionally, they were asked for their subjective need for psychooncological counselling. RESULTS: The correlation between the assessment instruments is low to medium. The number of patients above the cut-off criteria varies quite a lot according to the instrument (10% to 66%). Therefore, the congruence between the instruments' indications is quite low. Patients with and without subjective need do not differ in personal data but in distress scores. CONCLUSIONS: Recommended instruments for distress assessment in psychooncology measure different areas of distress. They do not sufficiently agree in indicating a patient's need for psychooncological treatment. Hence, one should neither compare results of studies using different assessment instruments nor implement a screening without reflecting the used instrument's characteristics compared to the others. The subjective need seems to provide additional information to the assessment. At present, the combination of an assessment instrument and patients' subjective need is seen as a best practice for identifying patients in need of psychooncological treatment.

Disseminated tumor cells from the bone marrow of patients with nonmetastatic primary breast cancer are predictive of locoregional relapse.

BACKGROUND: Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR). PATIENTS AND METHODS: Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2). RESULTS: A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037). CONCLUSIONS: DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.

Breast Cancer Update 2014 - Focus on the Patient and the Tumour.

The therapy for patients with breast cancer has developed markedly in the past ten years. Our understanding of the molecular biology of tumours and the characteristics of the patients has shaped the recent advances. In this review we present the latest knowledge about the therapy for breast cancer. There are new tests and options not only in the field of anti-HER2 therapy but also in the management of triple negative and hormone receptor-positive patients. Comprehension of prognosis and therapeutic response to chemotherapies is little by little helping to define patient groups who will not respond to chemotherapy or who do not need treatment because their prognosis is extremely good. In the field of anti-HER2 therapy, work is continuing on the development of drugs suitable for and able to overcome trastuzumab resistance. For hormone receptor-positive cancers, we now have a better understanding of which therapy groups will benefit from which anti-endocrine drugs, and which will be able to overcome a possible resistance (treatment of the PI3K pathways, inhibition of the cell cycle). Molecular tests are still being evaluated with regard to the clinical situations in which they may have the greatest relevance for therapeutic decision-making; however, evidence is also increasing as to the fields in which good predictions for the prognosis can be obtained. On the whole, more work is needed to promote our understanding of the new developments in diagnostics and therapy and to involve both physicians and patients equally in the procedures.

Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network.

Progress has been made in the treatment of metastatic breast cancer in recent decades, but very few therapies use patient or tumor-specific characteristics to tailor individualized treatment. More than ten years after the publication of the reference human genome sequence, analysis methods have improved enormously, fostering the hope that biomarkers can be used to individualize therapies and offer precise treatment based on tumor and patient characteristics. Biomarkers at every level of the system (genetics, epigenetics, gene expression, micro-RNA, proteomics and others) can be used for this. This has led to changes in clinical study designs, with drug developments often only focusing on small or very small subgroups of patients and tumors. The screening and registration of patients and their molecular tumor data has therefore become very important for the successful completion of clinical studies. This new form of medicine presents particular challenges for patients and physicians. Even in this new age of genome-wide analysis, the focus should still be on the patients' quality of life. This review summarizes recent developments and describes how the PRAEGNANT study network manages the aforementioned medical challenges and changes to create a professional infrastructure for patients and physicians.

Trastuzumab Administration in Patients with Metastatic Breast Cancer - Experience of a Large University Breast Center.

Background: Administered either alone or in combination with various cytostatic, endocrine or targeted therapies, trastuzumab significantly improves the prognosis of patients with HER2-positive breast cancer. As trastuzumab is effective across multiple lines of therapy in the metastatic setting (treatment beyond progression: TBP), it is often administered over a long period of time. The aim of this study was to evaluate the tolerability and clinical practice of long-term trastuzumab administration (> 1 year) in metastatic breast cancer patients treated in a large university breast center. Methods: Metastatic breast cancer patients who received at least 18 cycles of trastuzumab administered every three weeks at the University Gynecological Hospital of Tuebingen between 1999 and 2012 were included in this retrospective study. Typical combination drugs, side effects, and the impact of administration on left ventricular ejection fraction (LVEF) were investigated. Results: 72 patients were eligible for inclusion in the study. The mean number of administrations was 50.14 (SD: 27.51). In 53 patients the principle of TBP was followed across an average of 2.4 therapy lines. Classic cardiac risk factors were present at the beginning of trastuzumab treatment in 34 patients (47 %). Seven patients (10 %) experienced a decrease in LVEF during treatment, 9 patients (13 %) had hypersensitivity reactions. Treatment was discontinued in two patients due to side effects (1â€Š× progressive LVEF decrease, 1â€Š× intolerance). Summary: The administration of trastuzumab across multiple lines of therapy was generally tolerated well. Cardiac risk factors were not a limiting factor. If regular cardiac monitoring is done, trastuzumab appears not only to improve survival but also helps preserve the quality of life of patients with HER2-positive metastatic breast cancer.

Clinical characteristics, pathological reevaluation, surgical management and adjuvant therapy of patients with endometrial stromal tumors.

PURPOSE: To review a single-center experience over a 27-year period in the management of endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) for insight into clinical characteristics, pathological diagnosis, surgical practice, adjuvant therapy and clinical outcome. MATERIALS AND METHODS: This was a retrospective study of women with histologically proven ESS and UES who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Available tumor tissue, as well as inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained. RESULTS: The study sample comprised ten patients with ESS and seven patients with UES. Primary surgical treatment consisted of total hysterectomy in nine patients (90.0 %) with ESS and six patients (85.7 %) with UES; one patient (10.0 %) with ESS and one patient (14.3 %) with UES underwent debulking surgery. All patients (100 %) from the ESS group and six patients (85.7 %) from the UES group underwent bilateral salpingo-oophorectomy. Seven women (70.0 %) with ESS and six women (85.7 %) with UES underwent lymphadenectomy. Median DFS was 83.8 months (95 % CI 80.6-87.0) and median OS was 232.6 (95 % CI 49.3-415.9) for patients with ESS; median DFS was 12.9 months (95 % CI 0-284.1) and median OS was 17.6 (95 % CI 0-37.0) for patients with UES. There was no significant difference in DFS between patients with ESS as compared with patients with UES. However, patients with ESS had a significantly better OS when compared to patients with UES (p = 0.011). CONCLUSION: ESS and UES are very rare uterine neoplasms. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with ESS or UES.

Prevalence of paternal perinatal depressiveness and its link to partnership satisfaction and birth concerns.

Depressive disorders have shown an increasing prevalence over the past decades. Growing evidence suggests that pregnancy and childbirth trigger depressive symptoms not only in women but likewise in men. This study estimates the prevalence of paternal perinatal depressiveness in a German community sample and explores its link to partnership satisfaction as well as birth-related concerns and concerns about the future. Data was gathered in a longitudinal study over the second and third trimester of their partner's pregnancy up to 6 weeks postpartum. In a two-stage screening procedure, 102 expectant fathers were assessed for symptoms of depression, anxiety, and partnership satisfaction using the Edinburgh Postnatal depression Scale (EPDS), the State/Trait Anxiety Inventory, a self-constructed questionnaire for birth concerns and the Questionnaire of Partnership. The prevalence of elevated depressive symptoms among expectant fathers was 9.8 % prenatally and 7.8 % postnatally. Prenatal relationship quality, prenatal EPDS scores, and birth concerns were significantly associated with and explained 47 % of the variance in paternal postnatal depressive symptoms. The prevalence of paternal depressive symptoms is a significant concern. Our findings point out the need for implementing awareness and screening for depressiveness in fathers in clinical routine in Germany as well as the necessity of developing a screening instrument for paternal birth-related anxiety.

The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse.

Overexpression of the HER2-receptor in early breast cancer (EBC) patients is associated with aggressive tumor behavior. However, women suffering from HER2-positive EBC benefit from trastuzumab treatment. As the HER2 status of the primary tumor may differ from that of disseminated tumor cells (DTC) in bone marrow (BM), the aim of this study was (1) to compare the HER2 status of the primary tumor (prim-HER2-status) with that of DTC (DTC-HER2-status) and (2) to analyze the influence of the DTC-HER2-status on patient survival. For this purpose, BM aspirates from 569 EBC patients were analyzed for the presence of DTC. The DTC-HER2-status was identified by a double-staining procedure against cytokeratin and the HER2-receptor. DTC were detected in 151 (27 %) patients. The concordance between the HER2 status of DTC and the primary tumor was 51 %. In patients with detectable DTC, mean disease-free survival was 77.44 (95 % CI 74.72-80.17) months for DTC-HER2-negative and 55.15 (95 % CI 48.57-61.79) months for DTC-HER2-positive patients (p = 0.044). The multivariate analysis showed that the DTC-HER2-status was an independent predictor of disease-free survival. In conclusion, the presence of HER2-positive DTC in EBC patients is associated with an increased risk of relapse. Due to the low concordance between the HER2 status of the primary tumor and DTC, only a minority (13 %) of the DTC-HER2-positive patients was treated with trastuzumab. These patients might, however, benefit from HER2-directed therapy.