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Background: Telomerase is a chromosomal enzyme that is often overexpressed in cancer cells, and thus represents a potential biomarker & drug target. We correlated telomerase expression (TEL) in primary breast tumors with survival following standard treatment. Methods: TEL was assayed by quantitative RT-PCR in 223 snap-frozen breast cancer specimens, & quantified as relative activity (RTA)to MCF-7 breast cancer cell-line. Patient staging (AJCC-6) was based on medical records. All patients received treatment as per standard protocols. 192 cases had at least 24-m f/u & evaluated for survival. TEL was correlated with nodal (N+) or distant metastases (M+), hormone receptor status (HR), progression free (PFS) and overall survival (OS). Results: Stage distribution was: Stage I (23), II (128), III (53), and IV (19). 47 cases received no chemotherapy and 136 had standard risk-adjusted chemotherapy. 153 patients were HR+. 132 were N+. With a median f/u of 40 months (range: 24-95 months), 53 deaths had occurred and 107 remained disease-free. TEL ranged from 0 to 119.5 RTA. 11 were TEL -ve (= 0; NoTEL), 110 were low expressors (0-10; LoTEL) & 113 had high expression (> 10; HiTEL), of these 68 were very high (> 20; VHiTEL). Compared with LoTEL, HiTEL were more likely to be N+ (77 vs. 36, χ2 test, p < 0.05), HR-(54 vs. 16), lower 2-year PFS (60% vs. 86%), lower 2-year OS (80% vs. 97%) [χ2 test; each p < 0.001]. VHiTEL predicted metastatic disease (12/68 vs. 7/148, Fischer’s exact test, p = 0.003). By linear regression analysis, TEL was higher in HR-, M+ and higher stage disease (increment from I to IV), with regression coefficients being -11.2, 10.74 and 5.3 respectively (all p < 0.01). Telomerase positives received chemotherapy more often than NoTEL (Fisher’s exact test p < 0.05). HiTEL & LoTEL were distinct in OS & PFS despite similar treatment (Figure 1). Conclusions: Quantitative telomerase expression varies inversely with survival following standard therapy. Nodal metastases are more frequent in HITEL and distant metastases in VHiTEL, thus this may be used to decide for LN dissection & search for mets. Node-negative LoTEL patients may be spared chemotherapy, whereas survival remains poor in HiTEL cases despite conventional treatment.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]