A Polasik

Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?

Dissemination of tumour cells and the development of solid metastases occurs via blood vessels and lymphatics. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be detected in venous blood in patients with early and metastatic breast cancer, and their prognostic relevance has been demonstrated on numerous occasions. Repeated testing for CTCs and ctDNA, or regular so-called “liquid biopsy”, can be performed easily at any stage during the course of disease. Additional molecular analysis allows definition of tumour characteristics and heterogeneity that may be associated with treatment resistance. This in turn makes personalised, targeted treatments possible that may achieve both improved overall survival and quality of life.

Endocrine Treatment with 2 Years of Tamoxifen versus 2 Years of Exemestane in Postmenopausal Patients with High-Risk Early Breast Cancer and Persisting Circulating Tumor Cells - First Results of the SUCCESS C Endocrine Treatment Sub-Study

Background: Optimal choice and sequence of endocrine treatment following adjuvant chemotherapy in postmenopausal early breast cancer patients are still under discussion and treatment stratification factors are missing. Patients and Methods: Postmenopausal women with HER2-negative, hormone receptor-positive tumors and persisting circulating tumor cells (CTCs; assessed using the FDA-approved CellSearch® System, Janssen Diagnostics, LLC) after chemotherapy were randomized to 2 years of tamoxifen followed by 3 years of exemestane (tamoxifen-exemestane group, n = 54) or 5 years of exemestane (exemestane-only group, n = 54). CTCs were again assessed after the first 2 years of endocrine treatment. In addition, safety data were compared between the 2 groups. Results: The 2 groups were well-balanced with regard to baseline characteristics. The CTC clearance rate after 2 years was 89% in the exemestane-only group and 97% in the tamoxifen-exemestane group (exact Fisher test, p = 0.36). The safety profile showed good tolerability with few grade 3 or 4 adverse events in both groups. Conclusion: The similar CTC clearance rate after 2 years of endocrine therapy with exemestane or tamoxifen, and the safety profiles obtained may indicate comparable efficacy and tolerability of both endocrine treatment regimens. However, these results have to be confirmed by final survival and safety analysis.

Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis

BACKGROUND The prognostic relevance of circulating tumor cells (CTCs) at the time of primary diagnosis has been well established. However, little information is available regarding their prognostic relevance to follow-up care. METHODS The multicenter, open-label, phase III SUCCESS A trial compared two adjuvant chemotherapy regimens followed by 2 vs 5 years of zoledronate for early-stage, high-risk breast cancer patients. The presence of CTCs was assessed before and 2 years after chemotherapy using the FDA-approved CellSearch System. Overall survival (OS) and disease-free survival (DFS) were analyzed using univariate log-rank tests and multivariable Cox regressions. OS and DFS were measured starting from an assessment of CTCs 2 years after the completion of chemotherapy. All statistical tests were two-sided. RESULTS The sample included 1087 patients who participated in the translational research program of the SUCCESS A trial and for whom sufficient translational data were available regarding CTC status at baseline and at the 2-year follow-up visit. Two years after chemotherapy, 198 (18.2%) patients were CTC-positive. The median follow-up after this timepoint was 37 months. Cox regressions that included CTC status at baseline revealed that CTC status 2 years after chemotherapy had statistically significant and independent prognostic relevance for OS (hazard ratio [HR] = 3.91, 95% confidence interval [CI] = 2.04 to 7.52, P < .001) and DFS (HR = 2.31, 95% CI = 1.50 to 3.55, P < .001). CONCLUSION The presence of CTCs 2 years after chemotherapy was associated with decreased OS and DFS. Based on these results, active individualized surveillance strategies for breast cancer survivors based on biomarkers should be reconsidered.

Abstract OT3-04-02: DETECT III and IV – Individualized CTC-based therapy of metastatic breast cancer

Background: Circulating tumor cells (CTCs) are found in patients with early and metastatic breast cancer (MBC), and both their prognostic and predictive value has been described already. There is growing evidence that CTC phenotype may differ from the primary tumor. However, CTC targeted therapy is not used in clinical routine, and treatment decisions often still are based on the primary tumor9s phenotype without considering CTC-characteristics. The aim of the DETECT studies is to investigate and evaluate the role of presence and phenotype of CTC for guiding therapeutic decisions in women with HER2-negative MBC. Trial design and eligibility criteria: In a joint screening for DETECT III and IV, women with HER2-negative MBC are tested for CTCs and their HER2-phenotype. CTC detection is performed by the FDA-approved CellSearch System® (Janssen Diagnostics, Raritan, USA). Patients with HER2-positive CTCs are randomized in the multicenter Phase III study DETECT III to a physician9s choice chemo- or endocrine therapy with or without additional HER2-targeted treatment with lapatinib. Women with only HER2-negative CTCs are recruited to the multicenter open-label phase II study DETECT IV. Postmenopausal women with hormone-receptor positive MBC are treated with everolimus and a physician9s choice endocrine therapy in DETECT IVa. Patients with hormone-receptor positive MBC and an indication for chemotherapy and patients with triple-negative MBC receive mono-chemotherapy with eribulin in DETECT IVb. Treatment efficacy will be evaluated based on the early available CTC clearance rate (in DETECT III and DETECT IVa) and progression-free survival (in DETECT IVb) respectively, as the primary endpoint; secondary objectives will be to estimate disease control rate, progression-free (DETECT III and IVa) and overall survival, toxicity and tolerability of treatments with lapatinib, everolimus and eribulin, and quality of life. Specific aims: Changes in CTC-dynamics during therapy and their HER2-phenotype may influence following therapy decisions. The DETECT studies evaluate the prognostic and predictive role of CTCs as well as the efficacy of CTC based therapy to enable the establishment of a more personalized therapy for patients with MBC that might lead to prolonged progressive free survival and/or improved quality of life. The accompanying translational research programs investigate various markers for molecular characterization of CTCs and prediction of therapy response. Present accrual and target accrual: More than 1550 patients with HER2-negative MBC have already been screened within the DETECT study program. Thus, it is the worldwide largest study concept with therapy decisions resulting from CTC-testing and CTC-phenotypization. Contact: For further information on the DETECT study program please contact www.detect-studien.de or studienzentrale.ufk@uniklinik-ulm.de. Citation Format: Polasik A, Schramm A, Friedl TWP, Rack B, Trapp E, Fasching PA, Taran F-A, Hartkopf A, Schneeweiss A, Muller V, Aktas B, Pantel K, Meier-Stiegen F, Wimberger P, Janni W, Fehm T. DETECT III and IV – Individualized CTC-based therapy of metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-02.

Mammakarzinom: Genetischer Risikotest kann die Chemotherapie ersparen

Der 21-Gen-Rezidivscore (RS) Oncotype DX ist als prognostischer/prädiktiver Test beim frühen Hormonrezeptor(HR)-positiven Brustkrebs validiert. Jetzt liegen 3-Jahres-Daten für Patientinnen vor, die auf Basis des Testergebnisses nur eine adjuvante endokrine Therapie erhalten haben.

Erratum to: Current role of liquid biopsy in metastatic breast cancer and future perspectives

Gynäkologe 2016 · 49:970–972 DOI 10.1007/s00129-016-3970-6 Published online: 26 September 2016