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Abstract Background Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited. Methods We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions. Results Median age at diagnosis of BMs was 56 years (22–90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)–positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000–2009 with 2010–2015 (51%–44%), whereas the percentage of patients with luminal-like tumours increased (28%–34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval [CI]: 6.7–8.0 months). One-year survival rate was 37.7% (95% CI: 35.2–40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0–13.4) compared with 5.9 months (95% CI: 5.0–7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9–5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001). Conclusions Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients. Highlights • The first analysis of 1712 patients of breast cancer patients with brain metastases (BMs) is presented. • Localisation of BMs was different depending on tumour subtypes. • Survival times differ depending on the subtype and localisation of BMs. • A change in the incidence of BMs over time was observed. [ABSTRACT FROM AUTHOR]

Background: We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear.Methods: The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points.Results: Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031).Conclusion: Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment. [ABSTRACT FROM AUTHOR]

Background:We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving neoadjuvant therapy (NT) with lapatinib is still unclear.Methods:The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points.Results:Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml−1). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031).Conclusion:Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml−1) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment. [ABSTRACT FROM AUTHOR]

Studies on the occurrence of injuries following consensual sexual intercourse (CSI) among patients treated by office-based gynecologists are lacking. This survey aimed to assess the presence and medical relevance of vaginal injuries after CSI in gynecological office-based practice, associated risk factors, and their significance for forensic medical assessment practice. All office-based gynecologists in Hamburg, Germany (n = 316), were asked to fill in a one-page questionnaire via a fax survey. The questionnaire covered various aspects such as having observed CSI-related injuries, injury severity, risk factors, and concomitant factors (bleeding, need for surgical care, hospitalization). Response rate was 43.2% (n = 115). Overall, 83.5% of office-based gynecologists reported having observed vaginal injuries after CSI at least once and 59.1% repeatedly. Regarding maximum injury severity, 52.1% observed mucosal erosions, 32.3% mucosa penetrating injuries, and 14.6% injuries penetrating the vagina. Having observed bleeding was reported by 56.3%, 28.1% had to perform surgical suture care, and hospital admission was initiated by 20.8%. Menopause (37.5%), use of objects (19.8%), alcohol, and/or drug use (16.7%) were reported as the most frequently observed associated risk factors. Vaginal injuries after CSI have been observed by the majority of office-based gynecologists in Hamburg involving a wide spectrum of severity, including the necessity of surgical care and hospital admission. Complementing published work in clinical and emergency medicine, these findings are highly relevant to the forensic evaluation of injuries in an allegation of sexual assault, as the severity of a vaginal injury in this setting does not necessarily support a conclusion on the issue of consent. [ABSTRACT FROM AUTHOR]

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

Background: Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking.Methods: We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe.Results: PTEN deletions were detected in 19% of no special type, 9% of lobular, 4% of tubular cancers and 46% in carcinomas with medullary features. 98.7% of deletions were heterozygous and only 1.3% were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p=0.0054), high-grade (p<0.0001), high tumor cell proliferation (Ki67 Labeling Index; p<0.0001), and shortened overall survival (p=0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity; p<0.0001 each, and CCND1 amplification; p=0.0020). PTEN deletions were also strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p=0.0430) and HER2 (p=0.0065). Remarkably the combined analysis of MYC, HER2, CCND1 and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. While cancers with one of these aberrations behaved only marginally different from cancers with none, disease outcome was markedly worse in cancers with two or more aberrations as compared to those with only one aberration (p=0.0002). In addition, the particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy.Conclusion: PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumor behavior. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells. [ABSTRACT FROM AUTHOR]

Background We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). Patients and methods A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. Results Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. Conclusion RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC. [ABSTRACT FROM AUTHOR]

Background: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer.Methods: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT-PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk).Results: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly high risk, showing shorter DFS, P<0.001, and OAS, P=0.001. Although both validation cohorts showed diverse risk and treatment profiles, this marker constellation was concordantly associated with shorter DFS and OAS (P<0.001 and P=0.075 for cohort B and P=0.043 and P<0.001 for cohort C, respectively). In multivariate analysis, this algorithm was the main independent prognostic factor. Cohort B: DFS, P=0.0065, OAS, not significant; cohort C: DFS, P=0.026, OAS, P<0.001.Conclusion: Activated leukocyte cell adhesion molecule and OPN mRNA expression has a strong discriminative impact on survival within cancer patients with low or negative expression of ER and HER2, so called 'high-risk' breast cancers, and might help in identifying patients who could benefit from new treatment approaches like targeted therapies in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Introduction: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. Material and Methods: Paraffin-embedded tissue of the primary and distant metastases (N=84) were collected and ALCAM immunohistochemistry was performed. Results: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra-class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope=0.773, p < 0.001, r^{2}= 0.504). Conclusion: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer. [ABSTRACT FROM AUTHOR]

Efficacy and quality of life (QoL) are key factors when selecting therapies for metastatic breast cancer (MBC) patients. The addition of targeted oral agents such as CDK4/6 inhibitors to endocrine therapy is the new standard for HR+ HER2- MBC and substantially prolongs progression-free survival. However more complex oral medication in oncology might require substantial improvement of patient management. Despite several advantages of oral treatments, patients become increasingly self-responsible and physician-patient contact is reduced. Adherence, maintaining patients' satisfaction and early detection management of side effects become important challenges and new ways of continuous support are needed. An eHealth-based platform could help to support therapy management and physician-patient interaction. PRECYCLE is a multicenter, randomized, phase IV trial in HR+ HER2- MBC. All patients (n = 960) receive the palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant). Primary study aim is the time to deterioration (TTD) of QoL in patients supported by two eHealth systems with substantially different functionality. To date (02/11/2019) in 64 centers 165 patients have been randomized to the different study arms: - CANKADO inform with only a personal login, documentation of daily drug intake and passive text information, but no further functions. vs. - CANKADO active with the fully functional CANKADO-based eHealth treatment support system (drug diary, QoL, AEs, automated recommendations, etc.). To evaluate QoL, the FACT-B questionnaire is completed at every visit. Primary objective is to test the hypothesis of superiority for TTD with regard to QoL (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in those merely receiving eHealth-based information (CANKADO inform). As little is known about relationships between behavioral patterns (e.g. adherence), genetic background and drug efficacy the trial also includes a large translational program that aims at discovery and validation of biomarkers concerning efficacy, toxicity, adherence and QoL. NCT03220178 EudraCT: 2016-004191-22. The authors. Pfizer. T. Degenhardt: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: GSM; Travel / Accommodation / Expenses: Cellgene; Travel / Accommodation / Expenses: Daichii Synkyo. P.A. Fasching: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Teva; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Puma Biotechnology; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Myelo Therapeutics GmbH; Research grant / Funding (self): BioNTech AG. D. Lüftner: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: astra zeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: tesaro; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: teva; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: L'oreal. V. Müller: Advisory / Consultancy: hexal; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: nektar; Honoraria (self), Advisory / Consultancy: eisai; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): astra zeneca; Honoraria (self): Novartis; Honoraria (self): teva; Honoraria (self): tesaro. I. Witzel: Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: medac. T. Decker: Advisory / Consultancy: Novartis. H. Tesch: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Novartis. S. Kuemmel: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Novartis; Advisory / Consultancy: astra zeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy: somatex; Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Advisory / Consultancy: puma biotechnology; Advisory / Consultancy: pfm medical; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD oncology. R. Wuerstlein: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: sandoz; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: astra zeneca; Advisory / Consultancy: Merck. C. Riese: Full / Part-time employment: CANKADO. T. Schinköthe: Full / Part-time employment: CANKADO. J. Schumacher: Full / Part-time employment: Palleos Healthcare Services Gmbh. N. Harbeck: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: sandoz; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: agendia; Advisory / Consultancy: astra zeneca; Advisory / Consultancy: Merck sharp and dohme; Advisory / Consultancy: odonate therapeutics; Advisory / Consultancy: seattle genetics; Honoraria (self): Genomic Health; Honoraria (self): Amgen; Honoraria (self): nanostring; Research grant / Funding (institution): MSD. M. Schmidt: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): astra zeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): pantarhei bioscience; Advisory / Consultancy: myelo therapeutics gmbh; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest [ABSTRACT FROM AUTHOR]