255PD - Correlation between circulating tumor cells (CTCs), PET/CT response and pathological complete response (PCR) in primary HER2-positive (HER2+) breast...

Date 29 September 2012
Event ESMO Congress 2012
Session Breast cancer, early stage
Topics Breast Cancer, Early Stage
Translational Research
Presenter Hatem Azim Jr.
Authors H.A. Azim Jr.1, F. Rothé1, C.M. Aura2, M. Bavington3, M. Maetens1, G. Rouas1, E. De Azambuja4, C. Sotiriou5, S. Di Cosimo6, M. Ignatiadis1
  • 1Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 2Molecular Pathology Laboratory, VHIO, 08035 - Barcelona/ES
  • 3Programming, Frontier Science, Kincraig/UK
  • 4Medical Oncology, Institute Jules Bordet, BE-1000 - Brussels/BE
  • 5Bctl - Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 6Medical Oncology, Istituto Nazionale Tumori, Milan/IT

Abstract

Background

Although CTC detection has been studied in patients receiving preoperative chemotherapy, fewer data exist for preoperative chemotherapy combined with anti-HER2 agents. Here, we report a sub-study of CTC detection within the NeoALTTO trial.

Methods

NeoALTTO is a randomized phase III trial in which patients with primary HER2+ breast cancer were randomized to trastuzumab, lapatinib or their combination for 6 weeks followed by the addition of paclitaxel for 12 weeks prior to surgery. Participation in the CTC sub-study was optional. Blood samples were prospectively collected at baseline, after 2 weeks of anti-HER2 treatment alone and prior to surgery. A total of 22.5mL of blood was reduced to 7.5mL using a modified ficoll procedure that was then processed using CellSearch®. Evaluation of HER2 expression in CTCs was performed using the CellSearch® HER2 profiling kit. CTCs with HER2 staining intensity of 2 + /3+ were considered as HER2+. Associations between CTC detection and primary tumor characteristics, pCR and PET/CT response (at week 2 & 6) were assessed using the chi-square test.

Results

Out of 455 patients randomized, samples for CTC analysis were available for 51 (11%) patients from 16 sites, of whom 11 (21%) had ≥ 1 CTC/22.5ml in at least one time point (Table 1). At baseline, week 2 and surgery, we detected ≥1 CTC/22.5ml in 5/46 (11%), 4/41 (10%), and 5/31 (16%) patients with evaluable samples respectively. HER2+ CTCs were still detectable after 18 weeks of preoperative treatment with anti-HER2 agents plus paclitaxel in 3/31 (10%) patients. No significant association was observed between CTC detection (either at baseline or week 2 or surgery), and clinicopathologic characteristics, pCR (p = 0.36) or PET/CT response at week 2 (p = 0.34) or week 6 (p = 0.90).

Conclusion

CTC detection does not appear to be associated with pCR in patients receiving preoperative anti-HER2 agents plus paclitaxel, acknowledging the lack of power within our study.

Patient Treatment arm CTC / HER2+ CTC (number per 22.5mL) pCR
Baseline Week 2 Prior to Surgery
1 L 0 0 2 /2 NO
2 L NA 2 /2 2 /2 NO
3 L 1 /1 0 0 NO
4 L NA 4 /3 NA NO
5 T 0 1 /0 0 NO
6 T 65 /52 0 2 /1 NO
7 L + T 0 0 1 /0 NO
8 L + T 1 /0 0 NA NO
9 L + T 1 /0 0 0 YES
10 L + T 1 /0 0 NA YES
11 L + T 0 1 /0 1 /0 YES

L: lapatinib; T: trastuzumab; NA: not applicable.

Disclosure

All authors have declared no conflicts of interest.