Cell-cycle complete response after neoadjuvant letrozole predicts superior relapse-free and overall survival: Long-term follow- up of the letrozole P024 study

Abstract

570 Background: The P024 study was a double blind randomized endocrine therapy trial that compared 16 weeks of letrozole 2.5 mg daily (LET) with tamoxifen 20 mg daily (TAM). LET proved to be more effective than TAM in terms of tumor response and rates of breast conservation therapy (1). Biomarker studies also indicated that LET was a more effective anti-proliferative agent, with greater declines in Ki67 values (2). However, in the P024 trial patients experienced a very low rate of pathological complete response (pCR). We have therefore proposed that a cell-cycle complete response (CCCR - in which tumor cell Ki67 staining is 1% or less in the surgical specimen) may be an alternative to pCR because CCCR indicates that the endocrine therapy was maximally effective in causing cell-cycle arrest. In initial studies we had already shown that CCCR is more common with LET than TAM (3), and also there was a strong association between the absence of a CCCR and the presence of HER2 gene amplification (4). In this study we examined the relationships between CCCR and relapse-free and overall survival. Methods: Per protocol, patients were followed yearly for breast cancer relapse, all cause mortality and breast cancer specific mortality. Relapse-free and breast cancer specific survival was examined according to CCCR status after patients had been followed for five years on adjuvant TAM. Results: Patients who received neoadjuvant LET and whose tumors exhibited a CCCR had superior relapse-free (log rank P=0.0077) and breast cancer specific survival (P=0.0006). Patients who received TAM with a CCCR had superior RFS (P=0.0224) but not breast cancer specific survival. Conclusions: This study supports the conclusion that CCCR may be a clinically useful measurement for patients who undergo neoadjuvant LET. The value of CCCR after neoadjuvant TAM is less clear. A prospective trial that incorporates information on CCCR into clinical decision making regarding adjuvant chemotherapy may be appropriate. 1. Ann Oncol 12, 1527–32 (2001) 2. Cancer Res 63, 6523–31 (2003). 3. J Steroid Biochem Mol Biol 95, 91–5 (2005). 4. J Clin Oncol 24, 3019–25 (2006). No significant financial relationships to disclose.