Abstract GS5-07: International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study

Abstract

Introduction As early breast cancer might relapse even after complete removal of breast and lymphnodes, the disease must persist in secondary sites. The detection of disseminated tumor cells (DTC) in the bone marrow (BM) has been described as a surrogate of residual disease. Various trials showed an impaired prognosis of DTC positive early breast cancer (EBC) patients. The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is a large international pooled analysis that aimed to assess the prognostic impact of DTC detection in patients with EBC. Methods A pre-specified protocol was followed, and centers known to practice BM sampling for DTC detection were contacted for individual patient data. Patients with EBC, with available follow-up data and BM sampling before any anti-cancer treatment were eligible. BM aspirates were collected at the time of primary surgery. DTC were identified by antibody (A45-B/B3, AE1/AE3, 2E11 and E29) staining against cytokeratin. The DTC status was compared to other prognostic factors using the chi-squared test. Univariate log-rank test and multivariate cox regression were used to compare survival of DTC positive versus DTC negative patients. Results Individual data from 10,320 patients (11 centers from Europe and USA) were included with a median follow-up of 91 months. Of all patients, 2,823 (27.4 %) were DTC positive. DTC detection was associated with higher tumor grade, higher T stage, nodal positivity, ER and PR negativity, and HER2 positivity (all p<0.001). In univariate analyses, overall, breast cancer specific, disease-free and distant disease-free survival (OS, BCSS, DFS, DDFS) were significantly shorter in DTC positive patients with p-values of <0.001. Multivariate analyses showed the DTC status to be an independent prognostic marker for OS, BCSS, DFS and DDFS with hazard ratios (HR) and 95%-confidence intervals (CI) of 1.23 (95%-CI: 1.06-1.42, p=0.007), 1.38 (95%-CI: 1.11-1.72, p=0.004), 1.29 (95%-CI: 1.10-1.50, p=0.001) and 1.32 (95%-CI: 1.10-1.58, p=0.003), respectively. Conclusions Detection of DTC in the bone marrow is an independent prognostic marker in patients with non-metastatic breast cancer. Further studies should investigate the impact of DTC on metastatic cancer progression and their role for clinical decision making. Citation Format: Hartkopf AD, Brucker SY, Taran F-A, Harbeck N, von Au A, Naume B, Pierga J-Y, Hoffmann O, Beckmann MW, Rydén L, Fehm T, Aft R, Montserrat S, Walter V, Rack B, Schuetz F, Borgen E, Ta M-H, Bittner A-K, Fasching P, Fernö M, Krawczyk N, Weilbaecher K, Margelí M, Hahn M, Jueckstock J, Domschke C, Bidard F-C, Kasimir-Bauer S, Schoenfisch B, Kurt AG, Wallwiener M, Gebauer G, Wallwiener D, Janni W, Pantel K. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study [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 GS5-07.

Stellenwert der Liquid Biopsy beim Mammakarzinom

“…1). Kürzlich konnte diese Beobachtung in einer Metaanalyse von über 10 000 Patientinnen erneut bestätigt werden [8]. Allerdings bleibt nach wie vor unklar, welche Faktoren…”

Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel

“…Studies in the neoadjuvant or adjuvant therapy of early breast cancer are being performed and they are still waiting to be published. In early breast cancer patients, it is known that patients with a BRCA1/ 2 mutation in the case of neoadjuvant chemotherapy have a greater chance of a pCR 19 , 29 , 30 . Likewise there is evidence that women with a BRCA1/2 mutation have a somewhat better prognosis following chemotherapy than patients without a mutation 29 , 31 .…”

“…Studien in der neoadjuvanten oder adjuvanten Therapie des frühen Mammakarzinoms laufen und ihre Veröffentlichung steht noch aus. Bei Patientinnen mit frühem Mammakarzinom ist bekannt, dass Patientinnen mit einer BRCA1/ 2-Mutation bei einer neoadjuvanten Chemotherapie eine höhere Chance auf eine pathologische Komplettremission (pCR) haben 19 , 29 , 30 . Ebenso gibt es Anhaltspunkte, dass Frauen mit einer BRCA1/2-Mutation nach einer Chemotherapie eine etwas bessere Prognose haben als Patientinnen ohne Mutation 29 , 31 .…”

Update Mammakarzinom 2019 Teil 3 – aktuelle Entwicklungen bei der kurativen Behandlung von Mammakarzinom-Patientinnen: Eine Übersicht und Bewertung durch ein internationales Expertenpanel

“…Studien in der neoadjuvanten oder adjuvanten Therapie des frühen Mammakarzinoms laufen und ihre Veröffentlichung steht noch aus. Bei Patientinnen mit frühem Mammakarzinom ist bekannt, dass Patientinnen mit einer BRCA1/2-Mutation bei einer neoadjuvanten Chemotherapie eine höhere Chance auf eine pathologische Komplettremission (pCR) haben [19,29,30]. Ebenso gibt es Anhaltspunkte, dass Frauen mit einer BRCA1/2-Mutation nach einer Chemotherapie eine etwas bessere Prognose haben als Patientinnen ohne Mutation [29,31] Zur Frage der Resektionsränder bzw.…”