Abstract PD04-05: Prognostic Value of Circulating Tumor Cells According to Immunohistochemical Defined Molecular Subtype in Advanced Breast Cancer Patients

Abstract

Abstract Background: Breast cancer (BC) is not a single disease with variable morphologic features and biomarkers but, rather, a group of molecularly distinct neoplastic disorders. Four main molecular classes of BC have been distinguished by gene expression profiling, called luminal-A, luminal-B, HER2-positive and triple-negative (TN) cancers. These subgroups correspond reasonably well to clinical characterization on the basis of estrogen receptor (ER) and HER2 status, as well as proliferation markers or histologic grade. Correlating circulating tumor cells (CTCs) with molecular subtypes might identify subgroup of patients (pts) at different risks and groups that might benefit more from prognostic evaluation by CTCs. Patients and methods: We retrospectively analyzed 187 consecutive metastatic BC pts who had baseline CTCs enumeration performed between March 2005 and December 2009 by CellSearch. Pts were categorized in 3 prognostic groups in accordance to the number of CTCs, 0 CTC, <5 CTCs and ≥5 CTCs, and in 4 categories based on the tumour biology: luminal-A with ER >1%, any progesterone receptor (PgR), G1/G2, Ki67<30%; luminal-B with ER >1%, any PgR, G3, Ki67>30%; HER-2 positive with HER-2 overexpressed or FISH amplified; TN with both ER and PgR 0% and HER-2 not overexpressed/FISH not amplified. Kaplan-Meier method for survival analysis was used. Results: Median age at baseline was 56 years (range 31-78). CTCs were a strong predictive factor for overall survival (OS) in all pts (Log-Rank P<0.001), in pts with bone metastases (MTS) only (n=43; p=0.045), visceral MTS only (n=42; borderline significant p=0.08) and both bone and visceral MTS (n=74; P<0.001). The same figure was not observed in the few pts with only soft tissue MTS (n=28; p=0.315). Sixty-one (33%) pts had Luminal-A tumour, 58 (31%) Luminal-B, 53 (28%) HER-2 positive and 15 (8%) TN. CTCs were a significant prognostic factor in all molecular subtypes as shown in Figure 1. Conclusion: This large series confirms CTCs as an important prognostic factor for metastatic BC in all different molecular subtypes, but pts with 0 CTCs at baseline and TN or luminal B tumors seem to perform better as compared to other categories. Furthermore, pts with metastatic disease including bone and/or visceral sites benefited most from CTCs prognostic evaluation. Further studies with larger series and longer follow-up time could help identify metastatic BC subgroups in which CTCs analysis would be particularly useful and should be recommended. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-05.