Abstract P4-03-01: Role of disseminated tumor cell (DTC) in bone marrow (BM) detected at primary diagnosis on overall survival and central nervous system (CNS) recurrences in a cohort of 620 early breast cancer patients after 11 years follow up
Authors: Loirat Delphine , Bidard François-Clément , Chaltiel Léonor , Berger Frédérique , Dieras Véronique , de Rycke Yann , Alran Séverine , Kirova Youlia , Cottu Paul , Vincent- Salomon Anne , Sastre-Garau Xavier , Pierga Jean-Yves 
Published: May 2015

Abstract
Background: BM DTC detection is known to be a prognostic factor for distant metastasis and overall survival in early breast cancer. However, distant relapses may occur in patients with no DTC detected at time of primary cancer. In this study, we studied the impact of early breast cancer pathological features (including BM DTC status) on the incidence of CNS metastases.
Methods: In a cohort (1998-2005) of 620 early breast cancer patients in whom BM DTC were detected using an anti-cytokeratin antibody (A45B/B3) (Bidard et al., 2008, Clinical Cancer Research, outcome updating (median follow up 11y) on overall survival (OS) and distant metastasis free survival (DMFS) was assessed by log rank test and uni- and multivariate analyses. 137 patients of this cohort have a later metastatic relapse. Chi2 test were performed to compare patient with CNS metastasis and patients with other metastases locations. CNS metastasis survivals were estimated using Kaplan-Meier method and compared by log-rank test.
Results: At eleven-year median follow-up, the prognostic value of DTC detection was confirmed in the 620 patients cohort for OS (p=0.03 in multivariate analysis), but DTC were probably less involved in late metastatic events.
Distant metastases were diagnosed in 137 (22%) patients. In the course of the metastatic disease, 55 of these patients (40%) have been diagnosed with CNS metastases (parenchymal=30, leptomeningeal=10, both localizations=15), as first metastatic or later event. Patients with CNS metastasis were mostly less than 50 years old (60% vs 38%, p=0.01), pN0 (31% vs 10%, p=0.002), hormonal receptor status negative (54% vs 30%, p=0.007) and HER2 status positive (50% vs 22%, p=0.01). Strikingly, although DTC detection was associated with development of distant metastasis in the whole cohort, the occurrence of CNS metastasis was found to be higher in patients who had no DTC detected at primary diagnosis (p=0.016). From CNS metastasis, median survival was 7.8 months (8.3 months for parenchymal and 2.4 months for leptomeningeal recurrences). For HER2+ patients, the median survival after diagnosis of CNS metastasis was 16.6 months (N=15) and 4.1 months for Her2- patients (N=15).
Conclusions: After a long-term follow up, DTC remain an adverse prognostic factor in early breast cancer. Our study suggests that cancer cells with epithelial differentiation, as detected in the BM, are less prone to CNS dissemination. This study also confirmed previously reported determinants of CNS metastases (age, RH-, HER2+) in the pre-adjuvant trastuzumab era, but also showed that the outcome of HER2+ patients with CNS relapse was longer, probably due to HER2 targeted therapy during metastatic course.
Citation Format: Delphine Loirat, François-Clément Bidard, Léonor Chaltiel, Frédérique Berger, Véronique Dieras, Yann de Rycke, Séverine Alran, Youlia Kirova, Paul Cottu, Anne Vincent- Salomon, Xavier Sastre-Garau, Jean-Yves Pierga. Role of disseminated tumor cell (DTC) in bone marrow (BM) detected at primary diagnosis on overall survival and central nervous system (CNS) recurrences in a cohort of 620 early breast cancer patients after 11 years follow up [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-03-01.