Abstract P4-01-01: Circulating tumor cell (CTC) enumeration and HER2 assessment as predictors of breast cancer outcomes in the ALTTO (BIG 2-06, Alliance N063D) Trial

Background: CTCs are associated with clinical outcomes in metastatic breast cancer irrespective of ER/PR/HER2 status. Some data support the prognostic relevance of serial CTC enumeration relative to adjuvant chemotherapy in early stage breast cancer. However, data from a large scale study focused on HER2 directed therapy for HER2+ disease have been lacking. We therefore sought to prospectively evaluate the effect of trastuzumab +/- lapatinib on CTCs and assess the prognostic/predictive value of CTC monitoring in HER2+ early stage breast cancer patients (pts). Methods: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO; NCT00490139) Trial is an international, randomized, open-label phase III study of two targeted agents for HER2+ breast cancer. From June 2007 to July 2011, 8381 pts were randomised from 946 sites in 44 countries to 1 of 4 arms with sequential or concurrent chemotherapy: (i) 52 wks of trastuzumab (T); (ii) 52 wks of oral lapatinib (L); (iii) 12 or 18 wks of T followed by a washout and then 34 or 38 wks of L; or (iv) 52 wks of L+T. 540 (6%) pts provided optional informed consent and up to 30 mL peripheral blood suitable for CTC analyses at baseline with additional collections at 13 or 19 wks, 52 wks, 18 mos, 24 mos, and recurrence. CTC analyses are being conducted in three laboratories (Mayo Clinic Rochester, n=431; Institut Jules Bordet and University of Munich, n=109). 2-3 x 10 mL CellSave™ samples are pooled and processed at each time point for CTC enumeration and HER2 expression using the immunomagnetic/immunofluorescence assay (CellSearch™). A round-robin concordance project was done between Mayo Clinic Rochester and Institut Jules Bordet before embarking on the primary correlative work. Results: At baseline, 20% pts had detectable (i.e., ≥1) EpCAM+/CK+/DAPI+/CD45- CTCs, and 16% pts had detectable EpCAM+/CK+/DAPI+/CD45-/HER2+ CTCs. Correlative analyses with clinical outcome are ongoing with plans for completion by Fall 2014. Conclusions: CTCs were detected in 20% of pts with HER2+ early stage breast cancer. This is similar to the frequency of detection in mixed early stage breast cancer populations relative to ER/PR and HER2 status. Concordance of enumeration and HER2 assessments between the two experienced laboratories, and correlation between disease free survival and CTC findings (from serial samples collected at baseline, during the course of HER2 directed therapy, and at set intervals of follow-up) will be reported. Citation Format: Minetta C Liu, Brigitte Rack, Amylou C Dueck, David W Hillman, Michael B Campion, Monica M Reinholz, Kevin C Halling, Christos Sotiriou, Francoise Rothe, Marion Maetens, Ghizlane Rouas, Wolfgang Janni, Antonio C Wolff, Lyndsay N Harris, Julie R Gralow, Kathleen I Pritchard, Susan Ellard, Nguyet A Le-Lindqwister, Frances Boyle, Evandro De Azambuja, Martine J Piccart-Gebhart, Michail Ignatiadis, Edith A Perez. Circulating tumor cell (CTC) enumeration and HER2 assessment as predictors of breast cancer outcomes in the ALTTO (BIG 2-06, Alliance N063D) Trial [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 P4-01-01.