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Background Studies leading to the approval of trastuzumab emtansine (T-DM1) have been conducted without pertuzumab as previous therapy. Therefore data about patient characteristics and the efficacy of T-DM1 after a treatment with pertuzumab is scarce. Aim of this study was to analyze a real world patient cohort of advanced breast cancer (aBC) patients, who were treated with T-DM1 after a treatment containing pertuzumab in the metastatic setting with regard to patient characteristics and progression free survival (PFS). Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for metastatic breast cancer patients with focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible for this registry. Collected data comprises all relevant patient and tumor characteristics, therapies, adverse events, quality of life, patient reported outcomes, response and survival (PFS/OS). Here we report on the patient characteristics and PFS data for HER2 positive patients treated with T-DM1 after a treatment with pertuzumab. Patients had to be included before or at the beginning of the T-DM1 therapy. Results A total of 58 patients could be identified, who were suitable for the analysis. Of those 34 were treated in the second line, 14 in the third line and 10 in the fourth line or higher. Most of the pertuzumab therapies before T-DM1 were conducted in first line (n=46; 79.3%). Median PFS for all patients was 4.8 months (95% CI: 3.0-7.8 months). Median PFS for patients treated in the 3rdline and 4thline or higher was 4.2 months(95%CI: 2.3 - NA) and 4.0 months (95%CI: 1.8-N.A.), respectively. In patients treated 2ndline with T-DM1 PFS was 7.7 months (95%CI: 2.8 – 12.2). Conclusion T-DM1 is effective as 2ndand further line therapy following pretreatment with pertuzumab. Overall PFS was about 5 months with 7.7 months as 2nd-line therapy. The PFS in higher therapy lines might be shorter. As the sample size of this real world cohort was rather low and analyses have to be considered exploratory, this data need to be confirmed in studies with a larger sample size. Citation Format: Schneeweiss A, Lux MP, Hartkopf AD, Volz B, Kolberg H-C, Hadji P, Tesch H, Haeberle L, Ettl J, Lüftner DI, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Overkamp F, Huober J, Taran F-A, Janni W, Wallwiener D, Brucker SY, Fasching PA, Fehm TN. Progression free survival (PFS) and overall survival (OS) of patients treated with trastuzumab emtansine (T-DM1) after previous treatment with pertuzumab in patients with advanced breast cancer (NCT02338167) [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 P6-17-22.

Purpose: This analysis describes comprehensive real-world data concerning the use of anti-HER2 therapies in HER2 positive metastatic breast cancer (MBC). Specifically, it describes the therapy patterns of treatments with trastuzumab (TZM), pertuzumab+trastuzumab (PTZ/TZM), lapatinib (LAP) and trastuzumab emtansine (T-DM1). Methods: The PRAEGNANT study is a real-time, real-world registry for patients with MBC. Patients can be registered for PRAEGNANT at any time during the course of their metastatic disease and are followed up until death. All therapy lines are documented. This analysis presents the utilization of anti-HER2 therapies as well as therapy sequences. Results: Of 1936 patients within PRAEGNANT at the time of database closure 451 were HER2 positive (23.3%). Within the analysis set (417 patients after an unilateral breast cancer diagnosis), of which 53% were included in PRAEGNANT in the 1stline setting, 241 were treated with TZM (58%), 237 with PTZ (57%), 85 with LAP (20%) and 125 with T-DM1 (30%) during the course of their therapies. The sequence PTZ/TZMàT-DM1 was given to 51 patients (12%). Worse ECOG, negative hormone receptor status, and visceral or brain metastases were associated with a more frequent use of this therapy sequence. Most patients received T-DM1 after a therapy with pertuzumab. Conclusions: Both novel therapies (PTZ/TZM and T-DM1) are utilized in a high proportion of HER2 positive breast cancer patients. As most patients receive T-DM1 after pertuzumab real world data might help to understand whether this sequence has similar efficacy like in the approval study. Citation Format: Lux MP, Hartkopf AD, Huober J, Volz B, Taran F-A, Overkamp F, Hadji P, Tesch H, Haeberle L, Ettl J, Lueftner DI, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Fasching PA, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Kolberg H-C. Therapy landscape of patients with metastatic, HER2 positive breast cancer - Data from the real world breast cancer registry PRAEGNANT (NCT02338167) [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 P6-17-37.

Background During the last decades the treatment of advanced breast cancer (ABC) patients has improved due to a variety of new treatment strategies. Nevertheless, many ABC patients are faced with limited prognosis, and their treatment remains a challenge. New targeted therapies complement the well-established treatment options for ABC (CDK4/6 inhibition, anti-endocrine, chemotherapy, antibody based and bone related therapies), leading to improved treatment regimens tailored to the needs of special patient sub-populations. SPECIFIC AIMS/TRIAL DESIGN The PRAEGNANT network study is conducted as an academic, prospective registry and diagnostic translational study, accompanied by biomaterial collection. The pilot phase in more than 60 centers aims at including 3500 ABC patients. The primary objective is to discover biomarkers, which predict progression free survival (PFS). Secondary objectives include overall survival (OS), breast cancer specific survival, objective response rate, patient reported outcomes (PRO), description of therapies used in the metastatic setting, therapy adherence, health economics for patients with ABC, incidence of (serious) adverse events and big data/ machine learning algorithms. The exploratory objectives comprise correlations of gene alterations and their influence on OS, PFS, side effects and PRO. Exploratory biomarkers are assessed at baseline and at every change of therapy. These biomarkers include gene expression profiling of the primary tumor and corresponding metastasis, somatic mutations (measured in the tumor and in circulating tumor DNA), germline genetic variations, epigenetic changes and miRNA variations. Furthermore, plasma and serum markers are assessed. If actionable molecular alterations are detected patients are informed and recruited into suitable studies if available. ELIGIBILITY CRITERIA: Any adult patient (>18 years) with the diagnosis of ABC and who is willing and able to sign the informed consent can be enrolled. STATISTICAL METHODS/TARGET ACCRUAL: The PRAEGNANT study as a prospective real world registry and diagnostic translational study aims to identify biomarkers in ABC patients, which may predict PFS. Target accrual for the pilot phase is 3500 patients. Each patient will be documented for up to 36 months with an estimated median PFS for all patients of 11 months across all treatment lines. Citation Format: Müller V, Huober J, Volz B, Overkamp F, Kolberg H-C, Hadji P, Haeberle L, Ettl J, Hartkopf AD, Lux MP, Lüftner DI, Wallwiener M, Taran F-A, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt A, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Fehm TN, Brucker SY, Wallwiener D, Schneeweiss A, Fasching PA, Tesch H. PRAEGNANT - Real world evidence, translational research, big and smart data: A prospective academic translational research network for the optimization of the oncological health care quality in the adjuvant and advanced/ metastatic setting (NCT02338167) [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 OT1-11-02.

Background Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Patients and methods Post-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Results Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84). Conclusions These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. Clinical Trials Number CFEM345DDE19.

Background: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life.Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL). Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors. Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 – 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences. Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL. Citation Format: Wallwiener M, Nabieva N, Haeberle L, Taran FA, Hartkopf AD, Volz B, Overkamp F, Brandl AL, Kolberg H-C, Hadji P, Tesch H, Ettl J, Lux MP, Lueftner D, Belleville E, Fasching PA, Janni W, Beckmann MW, Wimberger P, Hielscher C, Fehm T, Brucker SY, Wallwiener D, Schneeweiss A, Mueller V. Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-10.

Background For breast cancer patients with metastases which are not life threatening national and international guidelines recommend the exhaustion of all antihormonal therapeutic options before recommending chemotherapy. In Germany up to now only everolimus was an additional option to overcome endocrine resistance. CDK4/6 inhibitors recently became available in Germany (Nov 2011). Aim of this analysis was the identification of predictors for a decision against an antihormonal treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for metastatic breast cancer patients. Besides biomarker research the description of real-world treatment data was one of the main study aims. This analysis was restricted to first line metastatic patients who were hormone receptor (HR) positive and HER2 negative. First, predictors were identified with a multiple logistic regression model. Then patients, who received chemo or not ,were compared with regard to overall survival using Cox regression analysis with the predictors for chemotherapy from above and additionally chemo status (yes/no) Results A total of 389 HR-positive and HER2-negative patients with detailed treatment information were included during the 1st line therapy into PRAEGNANT. Of those 173 (44.5%) received a chemotherapy, 190 an antihormone therapy (AHT) (48.8%), and 26 (6.7%) everolimus+AHT. In the multiple logistic regression model, older patients, lower graded tumors, bone only disease and previous adjuvant chemotherapy were associated with a lower rate of first line chemotherapies. BMI and number of concomitant diseases had no influence on the choice of first line metastatic therapy. In patients with visceral metastases 58.1% were treated with a 1st line chemo, while in patients with brain metastases or bone only metastases these numbers were 55.6% and 26.9%. Grading had an influence with patients having a G1, G2 and G3 tumor receiving 1st line chemo in 28.0%, 38.4% and 63.2% of the cases respectively. Patients who received chemo seemed to have a worse overall survival than patients who did not receive chemo (adjusted HR 1.58; 95% CI, 0.89 to 2.18). However, this result was not signifcant (p = 0.12). Overall survival was primarily influenced by ECOG and location of metastasis Conclusion The usage of chemotherapy can be predicted with age, metastasis pattern, grading and previous use of chemotherapy. However, we could not show that patients benefited from chemotherapy. On contrary, there was a tendency that patients treated with chemotherapy had poorer overall survival. Further studies with larger sample sizes are needed to confirm this claim. Citation Format: Huober J, Fasching PA, Taran F-A, Volz B, Overkamp F, Kolberg HC, Hadji P, Tesch H, Haeberle L, Ettl J, Hartkopf AD, Lux MP, Lueftner D, Wallwiener M, Mueller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Fersis N, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Wallwiener D, Brucker SY, Schneeweiss A, Fehm TN. Factors associated with first line chemotherapy use in patients with hormone receptor positive, HER2 negative metastatic breast cancer – data from the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-07.

Background: Despite novel, targeted therapies, metastatic breast cancer patients have an extremely unfavourable prognosis. Prognostic and predictive factors for patients with advanced breast cancer are not well understood. Molecular assessment of the patient and the tumor in the metastatic situation is not routinely performed despite advances in molecular precision medicine indicating great benefit to this patient group. Here we present early findings from the first 142 patients of a prospective molecular breast cancer registry with completed transcriptomic profiling. Methods: The PRAEGNANT study proctocol (NCT02338767) is a molecular registry designed to provide an infrastructure for the real-time comprehensive analysis of tumor and patient molecular characteristics under study conditions. Formalin fixed paraffin embedded tumors have been used from this registry to identify molecular, transcriptomic predictors for overall survival (OS). Known clinical correlates for OS (e.g. hormone-receptor status, age at diagnosis, and BMI) were analyzed by Cox proportional hazard ratios, and compared to transcriptomic markers of outcomes. Transcriptomes for all patient tumors were sequenced on the Illumina sequencing platform, and analyzed by RSEM to estimate transcripts per million (TPM) values for each gene isoform. Log-TPM values were used in established (PAM50) and novel (hierarchical clustering) expression-based subtyping of tumor samples. Expression-based subtypes were demonstrated to be strong prognostic indicators by Cox analysis. A Lasso regression machine learning algorithm was used to develop an expression-based predictive model of OS. Results: Hormone receptor positivity (HR=0.7, p Conclusions: Here we demonstrate using molecular profiling to develop prognostic signatures that out-perform standard clinical correlates of poor outcomes, even in a small subset of the total cohort. As the PRAEGNANT cohort expands these prognostic tools will continue to improve and supplement physician knowledge to improve patient outcomes. Citation Format: Szeto C, Benz S, Nguyen A, Rübner M, Wallwiener D, Tesch H, Hadji P, Fehm TN, Janni W, Overkamp F, Lueftner D, Lux MP, Wallwiener M, Beckmann MW, Huebner H, Ettl J, Hartkopf AD, Mueller V, Taran FA, Belleville E, Schneeweiss A, Soon-Shiong P, Rabizadeh S, Fasching PA. Developing prognostic indicators of poor outcomes in PRAEGNANT metastatic breast cancer cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-20.

Background Breast Cancer registries can help to understand how patient groups are treated outside clinical trials and what outcome is to expected for specific patient groups and therapy lines, which are not included into clinical trials. Here we present overall survival data according to therapy lines, patient and tumor characteristics. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible for this registry. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the comparison of overall survival data for different patient groups. For that analysis was restricted to patients included in the first therapy line for subgroup comparisons. Only for the analysis of the effect of therapy line on overall survival the complete dataset was used. Results A total of 1854 patients took part in this analysis. Of those 1016 were included first line, and 340, 213 and 285 patients 2nd line, 3rd lin4 and 4th line or higher respectively. A total of 339 deaths were observed. Two year survival rates (2Y-OS) for these groups were 75%, 65%, 57% and 36% (p(log-rank) Conclusion This breast registry included patients over all therapy lines however mainly during the 1st line of therapy. Simple patient and tumor characteristics can classify patients into patients with differently favourable prognosis. Patients with HER2 positive disease had the best overall survival, while TNBC and luminal B like patients had the worst prognosis. As most of the patients were luminal A like 43% of all deaths occured within the group of luminal A like patients, which will need further focus for therapy development in the future. Citation Format: Taran F-A, Fasching PA, Volz B, Huober J, Overkamp F, Kolberg HC, Hadji P, Tesch H, Haeberle L, Ettl J, Lux MP, Hartkopf AD, Lueftner D, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Fersis N, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A. Overall survival of metastatic breast cancer patients – data from the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-09.

Background Patients’ compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Aims: To investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. Methods: We included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance coverage (private/statutory), type of care (gynecological/general), region (West/East Germany), depression, chemotherapy, hormone therapy, pain medication, antidepressants, and the number of co-medications were included as covariates. Results: The mean ages in the group of women

Background: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

Background New treatment strategies for metastatic breast cancer (mBC) are mainly driven by therapies against specific targets. BRCA mutations are one of the few established actionable targets, with PARP-Inhibitors and Platinum showing high efficacy in mBC. Hereditary cancer testing panels are now broadly used for identification of individuals with BRCA1/2 mutations who may benefit from these therapies. Many of these panels also contain other predisposition genes involved in BRCA-related DNA repair pathways, but the clinical relevance of mutations in these genes remain unclear. The aim of this study was to describe the mutation rates of BRCA1/2 and panel-based predisposition genes, and the associated clinical characteristics of individuals with these mutations, in a prospective cohort of mBC patients. Methods The PRAEGNANT mBC registry (NCT02338167) is a prospective registry for metastatic breast cancer patients with a focus on molecular biomarkers. Patients receiving any therapeutic regimen are eligible for this registry. Germline DNA was collected at study entry and genotyped for 37 cancer predisposition genes including BRCA1 and BRCA2. The frequency of mutations in each gene was determined, and associations between mutations and patient and tumor characteristics, metastatic pattern, and overall survival were assessed. Results Mutations in established high (odds ratio (OR)>5.0) and moderate risk (OR>2.0) breast cancer genes (BRCA1/2, PALB2, CHEK2, ATM, RAD51D, BARD1, and MSH6) were seen in 123 of 1462 tested patients with mBC (8.4%). BRCA1 and BRCA2 mutations were seen in 1.4% and 2.9% of patients respectively. Most frequently mutated non-BRCA panel genes were CHEK2, PALB2 and ATM with 2.8%, 0.8% and 0.6% of patients. Mutation frequency varied with regard to patients who developed brain metastases, visceral metastases or bone only metastases. BRCA1 or BRCA2 mutations were seen frequently in patients with brain (5.3%) or visceral metastases (5.2%), but were present in only 2.5% patients with bone only metastases and 1.5% of patients with lesions in other locations. Panel genes were equally distributed among all metastatic patients. PALB2 mutations (n=11) were only seen in patients with brain (1.9%) and visceral metastases (0.9%), but not in patients with bone metastases or other locations. 36.4% (N=4) of all patients with PALB2 mutations developing a brain metastasis. When adjusted for other mBC prognostic factors, a mutation (all genes) was associated with an unfavorable prognosis (HR: 1.50; 95%CI: 1.04 to 2.30, p=0.03). Mutation frequencies were similar according to therapy lines. All other associations with molecular subtypes and risk factors were similar to primary breast cancer cases. Conclusion Mutations in high and moderate risk breast cancer genes were frequent in metastatic breast cancer patients. The frequency was substantially higher than the 4 to 5% mutation frequency observed among unselected primary breast cancer patients, but is consistent with recent results from studies of metastatic prostate cancer patients. Patients with brain and visceral metastases had the highest BRCA mutation rates. Results suggested that PALB2 mutations may be more frequent in patients with brain metastases. Citation Format: Fasching PA, Hu C, Hart SN, Polley EC, Lee KY, Gnanolivu RD, Lilyquist J, Hartkopf AD, Taran FA, Janni W, Hadji P, Tesch H, Haeberle L, Ettl J, Lux MP, Lueftner D, Wallwiener M, Mueller V, Beckmann MW, Belleville E, Wimberger P, Untch M, Kolberg H-C, Fehm TN, Overkamp F, Wallwiener D, Brucker SY, Schneeweiss A, Couch F. Cancer predisposition genes in metastatic breast cancer – Association with metastatic pattern, prognosis, patient and tumor characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD1-02.

BACKGROUND The double blind, placebo-controlled BOLERO-2 trial demonstrated a significant doubling of progression free survival (PFS) with EVE and EXE compared to EXE alone for postmenopausal women with hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) BC after recurrence/progression on non-steroidal aromatase inhibitors (NSAI) (Baselga J, et al. NEJM. 2012). The 4EVER study further evaluates the combination of EVE+EXE in a broader population to obtain greater insights and presents an extensive exploratory translational research program. SPECIFIC AIMS/TRIAL DESIGN 4EVER is a German multi-center, open-label, single-arm trial. 300 patients will receive EVE (10 mg/d)+EXE (25 mg/d) within clinical practice. The primary objective is to assess the overall response rate (ORR), the secondary objectives include PFS, overall survival, safety, quality of life (QoL), health utilities and health care resources. The exploratory biomarker objectives include pharmacogenetics, bone-turnover biomarkers, presence and molecular characteristics of circulating tumor cells, correlation of response to EVE+EXE with proteomics, and the influence of age, performance status, cancer activity and inflammation on anxiety and depression. Exploratory biomarkers are assessed at baseline and after 4, 12, and 24 weeks of treatment. ELIGIBILITY CRITERIA: Main inclusion criteria are postmenopausal women with metastatic or locally advanced ER+, HER2- BC, not amenable to curative treatment by surgery or radiotherapy, refractory to NSAI and with at least one lesion that can be accurately measured or bone lesions lytic or mixed (lytic+sclerotic) in the absence of measurable disease. STATISTICAL METHODS/TARGET ACCRUAL: The study is designed as an open-label, single-arm, phase IIIB trial to assess the efficacy and safety of EVE plus EXE in postmenopausal women with hormone receptor positive breast cancer progressing following prior therapy with NSAI. The primary objective is to estimate the ORR. Therefore, no statistical hypothesis or model is underlying the analysis. The ORR, i.e. best overall response of complete response (CR) or partial response (PR), as well as individual response categories CR, PR, stable disease (SD), progressive disease (PD) or unknown will be summarized using frequency tables together with their associated two-sided exact 95% confidence intervals (Clopper-Pearson method). The full analysis set will be used for the primary efficacy analysis. The primary efficacy and safety analysis will be conducted on all patient data at the time all patients who are still receiving study drug will have completed at least 24 weeks of treatment (or discontinued prematurely). The study plans to randomize 300 patients over a 1-year accrual period. The expected trial duration from activation to reporting of ORR is about 2 years. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-09.

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

Background This study aims to determine the role of patient expectations as potentially modifiable factor of side-effects, quality of life, and adherence to endocrine treatment of breast cancer. Patients and methods A 2-year prospective clinical cohort study was conducted in routine primary care with postoperative patients with hormone-receptor-positive breast cancer, scheduled to start adjuvant endocrine treatment. Structured patient-reported assessments of side-effects, side-effect expectations, quality of life, and adherence took place during the first week post-surgery and after 3 and 24 months of endocrine treatment. Results Of 111 enrolled patients, at 3 and 24 months, 107 and 88 patients, respectively, were assessed. After 2 years of endocrine treatment, patients reported high rates of side-effects (arthralgia: 71.3%, weight gain: 53.4%, hot flashes: 46.5%), including symptoms not directly attributable to the medication (breathing problems: 28.1%, dizziness: 25.6%). Pre-treatment expectations significantly predicted patient-reported long-term side-effects and quality of life in multivariate models controlling for relevant medical and psychological variables. Relative risk of side-effects after 2 years of endocrine treatment was higher in patients with high negative expectations at baseline than in those with low negative expectations (RR = 1.833, CI 95%, 1.032–3.256). A significant interaction confirmed this expectation effect to be particularly evident in patients with high side-effects at 3 months. Furthermore, baseline expectations were associated with adherence at 24 months (r = -0.25, P = 0.006). Conclusions Expectations are a genuine factor of clinical outcome from endocrine treatment for breast cancer. Negative expectations increase the risk of treatment-specific side-effects, nocebo side-effects, and non-adherence. Yet, controlled studies are needed to analyze potential causal relationships. Optimizing individual expectations might be a promising strategy to improve side-effect burden, quality of life, and adherence during longer-term drug intake. Trial registration ClinicalTrials.gov Identifier: NCT02088710.

Background: Aromatase Inhibitors (AI) are well established as adjuvant treatment for postmenopausal (PMP) women with hormone receptor positive (HR+) early breast cancer (EBC). However, phase III clinical trials have reported higher rates of arthralgia associated with AI than tamoxifen. This study aims to collect real world data on the effects of AI-associated arthralgia on patient compliance, patient outcomes and on treatment of arthralgia. Methods: COMPACT is an open, prospective, non-interventional, non-randomized study (NCT00857012) run in Germany. PMP women with HR+ EBC who had been on adjuvant anastrozole (ANA) for 3–6 months were enrolled and stratified by initial adjuvant ANA or switch from tamoxifen. All patients received regular standardized information about breast cancer from baseline to week 20 to support treatment compliance. Data on demographics, arthralgia, related therapies, other side effects and QoL were collected at baseline, 3, 6 and 9 months. Primary endpoints are scaled data on arthralgia and compliance within the first year of ANA therapy. Secondary endpoints include incidence of arthralgia, therapy costs, reasons for non-compliance, and influence of arthralgia on clinical outcome. Results: Between Apr 2009 and Mar 2011, 2313 patients were enrolled, 2007 on upfront ANA and 306 on switch from tamoxifen. The mean age at baseline was 64.5 years, mean BMI 27.7. Only 17.0% of patients had received HRT prior to their EBC. At baseline, 41.9% reported symptoms relating to skeleton or musculature. 12.0% reported arthralgia existing prior to ANA treatment and 13.2% stated a worsening of pre-existing arthralgia or new arthralgia after starting ANA. Predictors for non-adherence to AI therapy were former non-adherence, general symptom load on the side effect scale GASE, and low benefit expectation at treatment start. Risk of arthralgia was related to BMI (lowest for patients with BMI ≤24.1 kg/m2, highest with BMI >30.5 kg/m2 at all time points; OR>1) and upfront therapy (switch patients had a reduced risk of 68% at 6 and 61% at 9 months compared to patients with ANA upfront, p = 0.002). Patients with prior chemotherapy had lower rates of arthralgia before start of ANA (10.4% vs 13.3%, p = 0.036) but higher rates after the start of ANA and before study start (27.0% vs 22.5%, p = 0.013). Patients with arthralgia showed higher compliance rates at all time points (p < 0.001). Conclusion: COMPACT identified arthralgia and musculoskeletal symptoms as common complaints in PMP women with EBC. ANA treatment both increased the number of women with such symptoms and aggravated these in some patients. Higher BMI and upfront AI predicted for risk of AI associated arthralgia. However, COMPACT also showed that AI-associated arthralgia did not lead to non-compliance in most patients. This data may help to better understand compliance issues with adjuvant AI treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-08.

Background Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. We assessed if there was any correlation between treatment-emergent adverse events during exemestane or tamoxifen treatment and clinical response. Methods: A retrospective analysis of the German cohort of the TEAM trial was performed to assess progression-free survival and overall survival in patients with and without menopausal symptoms or arthralgia/myalgia during adjuvant treatment with exemestane or tamoxifen. Results: A total of 1502 patients were included in this analysis; 739 patients received tamoxifen and 763 received exemestane. Patients reporting menopausal symptoms and patients reporting arthralgia/myalgia during tamoxifen or exemestane treatment had significantly longer overall survival and progression-free survival. The effect on overall survival was irrespective of treatment. Progression-free survival was significantly improved in exemestane-treated patients reporting menopausal symptoms or those reporting arthralgia/myalgia versus those not reporting these adverse events. There was no significant difference in progression-free survival between tamoxifen-treated patients reporting these symptoms versus those who did not. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that overall survival and progressionfree survival was significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. In this analysis, the effect on overall survival and progression-free survival was irrespective of treatment. Conclusions: Our results suggest that the occurrence of menopausal symptoms or arthralgia/myalgia during treatment with tamoxifen or exemestane is associated with significantly improved overall survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-02.

Background: Based on baseline bone mineral density (BMD), adjuvant chemotherapy or endocrine therapy for early breast cancer patients can lead to substantially increased fracture risk. A significant decrease of BMD >10% after 2 years of chemotherapy (CT) and/or endocrine therapy (ET) has been reported. In recent studies, zoledronic acid (ZOL) produced an increase in BMD in premenopausal and postmenopausal patients with breast cancer (ABCSG-12, Z-FAST, ZO-FAST, etc). In addition, a significant increase in disease-free survival (DFS) with ZOL vs no ZOL was observed in most of these studies. Methods: The aim of 2 single-center, placebo-controlled, randomized studies—Probone I and Probone II—was to investigate the effect of adjuvant treatment with ZOL on BMD in premenopausal women with early breast cancer treated with CT and/or ET. Patients with hormone-receptor-negative (HR−) breast cancer (Probone I) were treated with (neo)adjuvant CT; patients with hormone-receptor-positive (HR+) breast cancer (Probone II) were treated with ET alone or in combination with (neo)adjuvant CT. Randomized patients received ZOL 4 mg or placebo IV every 3 months for 24 months. The primary objective was the change in BMD at the lumbar spine between baseline and month 24 (measured by dual-energy X-ray absorptiometry [DXA]). Secondary objectives included DFS; BMD at total hip, femur, and os calcis; quantitative ultrasonometry (QUS) at os calcis and phalanges; markers of bone turnover (C-telopeptide of type I collagen [CTX] and N-terminal propeptide of type I procollagen [P1NP]); endocrine hormones (follicle-stimulating hormone [FSH], estradiol, testosterone, sex hormone-binding globulin [SHBG], parathyroid hormone [PTH], vitamin D, anti-Müllerian hormone [AMH], inhibin A/B, etc); pathologic fractures; and safety and tolerability. Results: 70 HR+ and 11 HR− breast cancer patients have been enrolled into the studies. The last patient will have been treated for 24 months by the end of June 2011. Conclusions: The effects of ZOL on lumbar spine BMD at 24 months and secondary endpoints will be presented at the meeting. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-19-03.

Background: TEAM is the largest AI phase III trial comparing exemestane with tamoxifen followed by exemestane as adjuvant breast cancer therapy in postmenopausal women. We performed a meta-analysis of three randomized sub-studies of the TEAM trial conducted in Germany, the Netherlands/Belgium and the United States to determine the effects on bone health. Methods: Patients were randomised to exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12 and 24 months’ treatment. Bone turnover markers were also measured. Results: 412 patients were evaluable. Patients in the tamoxifen group showed a mean increase in lumbar spine BMD of 1.2% from baseline to month 12 and 0.2% to month 24. Patients in the exemestane group showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in BMD at the lumbar spine between treatment groups (P Conclusions: After 24 months, exemestane treatment resulted in decreases in BMD and increases in bone turnover markers. In contrast, BMD was increased and bone turnover markers were decreased with tamoxifen. BMD and bone turnover changes appeared to stabilise after initial treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-08.

Gynaecologists and oncologists (listed below) met in November 2008 to draw LIP recommendations to be used as guidelines for adjuvant treatment with bisphosphonates for the prevention of tumour progression in receptor positive breast cancer patients based on the Currently available evidence. Malignant epithelial tumours usually disseminate into bone marrow. Because of the abundance of cytokines and the stimulating growth factors found there, this microenvironment is ideal for the survival and growth of cancer cells. A variety of growth factors such as transforming growth factor beta (TGF-beta) or insulin-like growth factor (IGF) are accumulated within the bone matrix and can be released by stimulated osteoclasts and become available for tumour cells. Therefore the bone and its microenvironment play an important role in tumour progression because cancer cells can survive in bone marrow and grow to become bone metastases. In addition, tumour cells can reenter in the circulation and form new metastases in more distant organs. Recently, various Studies have shown that adjuvant bisphosphonate therapy can improve disease-free survival in hormone receptor positive breast cancer patients. Due to medical need and because detailed guidelines for this therapeutic intervention are still lacking, twelve experts have Put together recommendations for adjuvant bisphosphonate therapy based on the currently available evidence. This critical consensus could help to encourage the use of appropriate adjuvant bisphosphonate therapy in these patients.

Background: The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Dayto-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). Materials and methods: We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. Results: Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (63) and 72 (63); P < 0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P < 0.01 and P < 0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. Conclusions: An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

OBJECTIVE: It is well documented that aromatase inhibitors (AI) are superior to tamoxifen as an adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer. However, compared with tamoxifen, an elevated incidence of arthralgia has been observed during AI treatment. Concerns have been raised that AI-induced arthralgia may dissuade patients from completing their full AI treatment course. Patient education on the possibility of experiencing arthralgia and the effective management of symptoms, if they appear, is important in helping patients adhere to AI treatment schedules and, consequently, in improving breast cancer outcomes. METHODS: In this paper, we discuss the potential mechanisms behind AI-induced arthralgia, review the frequency with which arthralgia occurs, and propose an algorithm specifically for the treatment of AI-induced arthralgia. As with joint pain in non-breast cancer patients, a sequential approach to disease management is recommended, involving modifications of the patient's lifestyle in addition to taking a stratified approach to pharmacological intervention with analgesia and anti-inflammatory medication. CONCLUSION: Knowing that joint symptoms can be managed in most patients may encourage patient-physician communication and treatment compliance. A specific treatment algorithm is proposed that may support doctors and patients when dealing with AI-induced arthralgia.

Third-generation aromatase inhibitors (AIs) are replacing tamoxifen as adjuvant therapy in postmenopausal women with hormone-sensitive breast cancer due to their superiority shown in several recent head-to-head trials. Healthy postmenopausal women normally experience age-related side effects, and in postmenopausal women with breast cancer, these symptoms may be exacerbated by adjuvant endocrine therapy. This review evaluates the current literature regarding bone health, lipid metabolism, cardiovascular disease, gynecologic health, and cognition in postmenopausal women receiving adjuvant AI therapy. The AIs -- anastrozole, exemestane, and letrozole -- are generally well tolerated: most adverse events are mild to moderate and common to menopause. Common short-term AI-associated toxicities are hot flushes, musculoskeletal complaints/arthralgia, and bone loss, all of which can be effectively managed. AIs may lack the cardioprotective and lipid-lowering effects of tamoxifen but, in contrast to tamoxifen, do not increase the risk of serious life-threatening thromboembolic or cerebrovascular events or endometrial cancer. Every patient should be individually assessed with respect to therapy risks and benefits. Lifestyle, comorbidities, and concomitant medications must be considered, and the importance of compliance to adjuvant therapy should be discussed before selecting a treatment regimen. The superior efficacy of adjuvant AI therapy will in most cases outweigh the risk of bothersome side effects that can be prevented or easily managed.

Recent studies suggest an inverse relation between breast cancer and osteoporosis. Oestrogen is important in the pathophysiology of both breast and bone, and although cumulative exposure to oestrogen may explain the link between breast cancer and bone mass, this has never been proved. The Marburg breast cancer and osteoporosis trial (MABOT) aimed to elucidate the relation between breast cancer and bone mass ascertained by ultrasonometry measurement and to investigate whether endogenous and exogenous exposure to oestrogen and reproductive correlates has a role in this association.We performed a case-control study including 2492 women (mean age+/-S.D., 54.4+/-10.3 years) in whom diseases and drug treatments known to affect bone metabolism, except for HT, had been excluded. All women underwent ultrasonometry measurement at the heel; 242 of the women had an incident breast cancer without a prior, specific pharmacological breast cancer treatment. The ultrasonometry variables - speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) - were calculated and compared in women with and without breast cancer. Because of significant intergroup differences in factors such as age, body mass index and exposure to oestrogen, a multiple linear regression analysis as well as a second analysis of ultrasonometry variables was undertaken using a randomly selected sample of 242 healthy women post-matched with the breast cancer group for possible confounding variables. Odds ratios were used to compare the relation between breast cancer risk and ultrasonometry heel measurements.Women with breast cancer were significantly older, weighed more, had a higher body mass index, were more likely to be parous and to have breast fed, were older at the menopause and had been exposed to oestrogen for longer than control women. In addition, the ultrasonometry variables speed of sound and the stiffness index T- and Z-score were significantly higher in women with breast cancer even after a matched pair analysis was performed (p0.001). Additionally, results of a multiple linear regression showed that women with breast cancer had a significantly higher SOS (p0.001), body weight (p0.05) and duration of breast feeding (p0.05) while osteoporotic fracture were reduced (p0.001). When women with breast cancer and their matched controls were finally grouped according to SOS and T-score quartiles, the odds ratios (95% confidence intervals) for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were 2.5 (1.4-4.3), 3.1 (1.8-5.3) and 4.7 (2.7-8.2) as well as 1.9 (1.1-3.2), 2.3 (1.3-3.9) and 2.9 (1.7-5.0), respectively.The ultrasonometry variables speed of sound, stiffness index, T- and Z-score are higher in women with an incident breast cancer than in healthy controls, even after post-matching for possible confounding variables. This association was confirmed in a multiple linear regression model. Women with SOS and T-score values in the higher quartiles have a greater risk of breast cancer than women in the lowest quartile. We found no association between the higher ultrasonometry variables and cancer specific characteristics or reproductive correlates such as age at menarche and menopause or cumulative oestrogen exposure. Although the biological mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than reproductive correlates, endogenous and exogenous exposure to oestrogen must play a part.

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

Higher breast density leads to a higher risk of breast-cancer coming along with a reduced sensitivity of mammography, the most important method for early diagnosis of breast cancer. HRT leads to an increase in breast density in up to (1/3) of treated women. Combined regimes of estrogen-progestin show a stronger influence than estrogen only. Changes of breast density appear almost entirely within the first year of administration and seem to be reversible after suspension of treatment within a few weeks. A possible solution of the dilemma is to perform mammography in asymptomatic premenopausal women during the first half of the menstrual cycle. In women with increased breast density using HRT it is recommended to modify the combination of hormones, change the application mode, or suspend HRT for a short period of 3 weeks prior to mammography. In symptomatic women with dense breasts, additive breast ultrasound is strongly recommended to reduce the otherwise high rate of missed breast cancers.

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

Changes in bone mineral density (BMD) and trabecular bone score (TBS) were assessed in 70 patients who received either zoledronate (ZOL) (n = 34) or placebo (n = 36) for 2 years. In premenopausal women with breast cancer treatment-induced bone loss, 24 months of intravenous ZOL treatment significantly increased the lumbar spine BMD and the TBS. The aim of this study was to compare the effects of 4 mg intravenous zoledronate (ZOL) versus placebo (PLB), every 3 months, on the lumbar spine (LS) bone mineral density (BMD) and the trabecular bone score (TBS) in premenopausal women with breast cancer (BC) treatment-induced bone loss. The TBS is a gray-level texture measurement which is related to the bone microarchitecture and considered to be independent of the BMD. Changes in BMD and TBS were assessed in 70 patients who were recruited in the double-blind, placebo-controlled ProBONE-II trial and randomized to receive either ZOL (n = 34) or PLB (n = 36) for 2 years. The changes were assessed at baseline and at 12 and 24 months after treatment initiation. Patients receiving ZOL showed a mean increase in LS BMD from the baseline to 12 (2.17 %) and 24 months (3.14 %) of treatment and a mean increase in the TBS of 2.41 and 0.75 %, respectively. Conversely, patients receiving PLB showed a mean decrease in the LS BMD from the baseline to 12 (−5.02 %) and 24 (−6.43 %) months and a mean decrease of −0.52 and −2.16 % in the TBS, respectively. Changes in the BMD and the TBS from the baseline to 12 and 24 months were all significantly different for ZOL compared to PLB (p

Objective: Because estrogens are important in the pathogenesis of both breast cancer and osteoporosis, it has been suggested that the risk of osteoporosis and breast cancer are inversely related. The aim of our study was to evaluate bone mineral density in patients with breast cancer. Methods: Speed of sound, broadband ultrasound attenuation, and the stiffness index of the calcaneus were measured in 1004 subjects (mean age 53.9 years) with an Achilles ultrasound bone densitometer. 148 patients had a history of breast cancer and 856 did not. Breast cancer patients were compared with healthy subjects matched for age, weight, body mass index (BMI), parity, and duration of breast feeding and estrogen exposure. Results: Overall, the patients with breast cancer were 4.4 years older and had higher body weight, BMI and parity, longer duration of breast feeding and estrogen exposure, and a significantly higher speed of sound and stiffness index than healthy controls. In the matched-pairs analysis, women with breast cancer had a higher speed of sound and stiffness index than the controls. Conclusion: Women with breast cancer have a lower risk of osteoporosis than controls. Although the biologic mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than cumulative estrogen exposure may play a role. Studies on larger populations are needed to evaluate this relationship.