C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance

Data from basic research suggests that amplification of the proto-oncogene c-myc is important in breast cancer pathogenesis, but its frequency of ampl ification and prognostic relevance in human studies have been inconsistent. In an effort to clarify the clinical significance of c-myc amplification i n breast cancer, we conducted a comprehensive literature search and a meta- analysis in which 29 studies were evaluated. The weighted average frequency of c-myc amplification in breast tumours was 15.7% (95% CI = 12.5-18.8%), although estimates in individual studies exhibited significant heterogeneit y, P < 0.0001. C-myc amplification exhibited significant but weak associati ons with tumour grade (RR = 1.61), lymph-node metastasis (RR = 1.24), negat ive progesterone receptor status (RR = 1.27), and postmenopausal status (RR = 0.82). Amplification was significantly associated with risk of relapse a nd death, with pooled estimates RR = 2.05 (95% CI = 1.51-2.78) and RR = 1.7 4 (95% CI = 1.27-2.39), respectively. This effect did not appear to be mere ly a surrogate for other prognostic factors. These results suggest that c-m yc amplification is relatively common in breast cancer and may provide inde pendent prognostic information. More rigorous studies with consistent metho dology are required to validate this association, and to investigate its po tential as a molecular predictor of specific therapy response. (C) 2000 Can cer Research Campaign.