Résumé
Background: CTC detection in blood is an independent prognostic factor in primary breast cancer with a detection rate from 20 to 25% (Pierga, CCR 2008, Rack B, JNCI 2014). Higher incidence of 35% of CTC has been reported in IBC (Pierga, Lancet Oncol 2012). Predictive and prognostic value of CEC for response to anti-angiogenic agents remains debated.
Methods: CTC and CEC were detected in 7.5 ml and 4 ml of blood respectively in the neoadjuvant setting of HER2 negative IBC (T4d) patients (pts) enrolled in the phase II multicentre trial BEVERLY 1, evaluating bevacizumab (15mg/kg q3w) in combination with sequential neoadjuvant CT of 4 cycles of FEC followed by 4 cycles of Docetaxel. The CellSearch™ System, combining EpCAM immunomagnetic selection followed by anti-cytokeratin (A45B/B3) and anti-HER2 staining for CTC and CD146 IMS and CD105 staining for CEC.
Results: From 12/08 to 09/10, 101 pts were included and 92 were evaluable for CTC and CEC. At baseline, 37 pts out of 92 had ≥ 1 detectable CTC (40%, 95%CI 30-50%). No correlation was found between CTC and CEC levels. A dramatic drop in CTC incidence (p<0.0001) was observed from baseline to the 1st follow-up analysis after 4 cycles (6%). There was a significant increase of CEC median number from baseline (12) to preoperative sample (130) (p <0.001) and a decrease (39) (p = 0.04) when CT and bevacizumab were interrupted for surgery. CTC detection at baseline independently predicted 3-year DFS: (73% vs. 41% for patients with <1 vs. ≥1 CTC/7.5 mL [p<0.001, HR 2.73 (1.48-5.04)]) and OS (94% vs.51% [p<0.001, HR 5.93 (2.49-14.10)]. Fourteen patients (15%) with no CTC detected at baseline and with complete pathological response (pCR) had a high 3-year DFS (93%) and OS (100%). CEC level under 20/4ml at baseline did not reach statistical significance as a favorable prognostic factor for DFS and OS (p = 0.055 and 0.066 respectively). CEC changes during treatment had no prognostic value.
Conclusions: We observed a high CTC detection rate of 40% in pts with HER2 negative IBC, including triple negative tumor, with a strong and independent prognostic value for DFS and OS. Combining pCR after neoadjuvant chemotherapy combined with bevacizumab, and CTC at baseline, isolates a subgroup of inflammatory breast cancer with excellent survival.
Citation Format: Jean-Yves Pierga, Francois-Clement Bidard, Aurelie Autret, Fabrice Andre, Thierry Petit, Florence Dalenc, Christel Levy, William Jacot, Jacques Bonneterre, Jean-Marc Ferrero, Pierre Kerbrat, Jerome Lemonnier, Francois Bertucci, Patrice Viens. Circulating tumor cells (CTC) but not circulating endothelial cells (CEC) are independent prognostic factors in neoadjuvant chemotherapy combined with bevacizumab in HER2 negative inflammatory breast cancer (IBC) in multicentre phase II trial BEVERLY1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 381. doi:10.1158/1538-7445.AM2015-381