Background: The collaborative DETECT study program represents one of the largest study program on metastatic breast cancer worldwide. The main objective of the DETECT trial is to evaluate the efficacy of individualized breast cancer treatment based on the presence and phenotype setting of circulating tumor cells (CTCs). Thus, the DETECT study program is one of the first clinical trial translating the role of CTC enumeration/phenotyping directly into treatment intervention within different breast cancer subtypes. Trial design: The DETECT III trial is a multicenter, randomized, phase III study to compare standard therapy alone versus standard therapy plus lapatinib in patients with initially HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. Patients with persisting HER2-negative circulating tumor cells (CTCs) can be included within the DETECT IV trial, a prospective, multicenter, open-label, phase II study including patients with HER2-negative metastatic breast cancer. Within the DETECT IV study setting postmenopausal patients with hormone-receptor positive metastatic breast cancer are treated with everolimus or ribociclib and endocrine therapy, while women with triple negative metastatic breast cancer or a hormone-receptor positive tumor and indication for chemotherapy receive eribulin. Specific aims: The DETECT study program comprises all breast cancer subtypes and therefore offers various up-to-date treatment options, generating a wealth of clinical data including long-term follow-up data, evaluated in a controlled setting of a single large clinical trial. The primary endpoint of the DETECT III trial is the comparison of patients receiving standard anticancer therapy with lapatinib and patients receiving standard anticancer therapy alone, with regard to the CTC clearance rate. The secondary objective of this trial is to assess the level of compliance to study procedures comparing the efficacy of lapatinib between given treatment groups (Progression free survival, overall response rate and dynamic of CTCs). Primary objective of the DETECT IV trial is to evaluate CTC clearance rate within the everolimus/ribociclib cohort and additionally assess progression-free survival defined as time interval from date of recruitment until progressive disease within the eribulin cohort. The main focal point of the extensive collaborative translational oncology research projects is to apply innovative biomarkers and assays focusing on molecular characteristics of CTCs. This “biological status” may give new information about CTCs potential function as liquid biopsy in order to determine their relevance for therapy prediction. Citation Format: Krause S, Friedl T, Romashova T, Fasching PA, Schneeweiss A, Müller V, Taran F-A, Arkadius P, Marie T, De Gregorio A, Meier-Stiegen F, Huober J, Janni W, Fehm T. DETECT III/IV study trial – The multicenter study program in patients with HER2-negative metastatic breast cancer and circulating tumor cells [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 OT1-10-01.

Selected patients with NOA may show ejaculated spermatozoa after a non-invasive repair of a left side varicocele, therefore avoiding testicular sperm extraction. Baseline serum FSH was a valuable predictor for ejaculated spermatozoa after treatment.

Background: Metastatic breast cancer (MBC) is usually an incurable disease and maintenance of quality of life (QoL) is one of the main aims of therapy. In patients with HER2-positive MBC taxane-based chemotherapy in combination with dual HER2 targeted therapy with trastuzumab and pertuzumab,is the standard of care. Adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients' QoL. The synergistic combination of dual HER2-targeted therapy with trastuzumab and pertuzumab plus endocrine therapy might offer a better treatment option for these patients. First clinical trials suggest an additional benefit when a CDK4/6 inhibitor is added to the combination of endocrine therapy and anti HER2 treatment. DETECT V is a randomized phase III study comparing the safety and efficacy of trastuzumab plus pertuzumab and the CDK 4/6 inhibitor ribociclib in combination with either endocrine therapy or chemotherapy. Trial design: Patients with HER2 positive and hormone-receptor positive MBC are 1:1 randomized to receive trastuzumab and pertuzumab combined with endocrine therapy and ribociclib or to chemotherapy with trastuzumab and pertuzumab followed by maintenance therapy with trastuzumab, pertuzumab, endocrine therapy and ribociclib. Chemotherapy and the endocrine agents can be chosen from a variety of available regimens according to the physicians discretion. Specific aims: The primary objective of this study is to compare safety and tolerability in both arms, as assessed by the occurrence of AEs during the treatment period. Secondary endpoints are progression free survival, overall survival, quality-adjusted survival using the quality-adjusted time without symptoms and toxicity (Q-TWiST) method. A translational program is included investigating detection and phenotyping of circulating tumor cells (CTC)-and the assessment of marker expression on CTCs in order to validate an endocrine responsiveness score. Present accrual and target accrual: The DETECT V trial started 2015 in the Dept. of Gynecology, University of Ulm and at the up to 120 sites in Germany. Until June 2018 97 patients with HER2-positive, hormone-receptor positive metastatic breast cancer have been enrolled. A sample size of 270 patients is planned. Contact information: Jens Huober, University of Ulm, Dept of Gynecology, Breast Center, jens.huober@uniklinik-ulm.de Sabrina Krause, University of Ulm, Dept of Gynecology, sabrina.krause@uniklinik-ulm.de Citation Format: Krause S, Friedl T, Fehm T, Romashova T, Fasching PA, Schneeweiss A, Müller V, Taran F-A, Polasik A, Tzschaschel M, De Gregorio A, Meier-Stiegen F, Janni W, Huober J. DETECT V/CHEVENDO – Comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in addition with CDK4/6 inhibition in patients with HER2-positive and hormone-receptor positive metastatic breast cancer [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 OT2-07-01.

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ZusammenfassungDie Streuung von Tumorzellen und Entstehung solider Metastasen findet sowohl über das Lymph- als auch das Blutsystem statt. Der Nachweis zirkulierender Tumorzellen (CTCs) und der zirkulierenden Tumor-DNA (ctDNA) im venösen Blut ist sowohl beim frühen als auch beim metastasierten Mammakarzinom möglich. Ihre prognostische Relevanz wurde bereits mehrfach bewiesen. Dabei ist die repetitive Untersuchung der CTCs bzw. ctDNA im Sinne einer regelmäßigen „liquid biopsy“ jederzeit und problemlos möglich. Durch die zusätzlichen molekularen Analysen ist es möglich, Tumorcharakteristika und ihre Heterogenität, die mit möglichen Resistenzen einhergehen, zu definieren. Dies ermöglicht den Einsatz einer personalisierten und zielgerichteten Therapie, um neben einem verlängerten Gesamtüberleben auch die Verbesserung der Lebensqualität zu erreichen.