Long-term impact of the 70-gene signature on breast cancer outcome

Publication Name: Breast Cancer Research and Treatment

Author(s): C. A. Drukker, H. van Tinteren, M. K. Schmidt, E. J. Th. Rutgers, R. Bernards, M. J. van de Vijver, L. J. van’t Veer

Several studies have validated the prognostic value of the 70-gene prognosis signature (MammaPrintR), but long-term outcome prediction of these patients has not been previously reported. The follow-up of the consecutively treated cohort of 295 patients (<53 years) with invasive breast cancer (T1-2N0-1M0; n = 151 N0, n = 144 N1) diagnosed between 1984 and 1995, in which the 70-gene signature was previously validated, was updated. The median follow-up for this series is now extended to 18.5 years. A significant difference is seen in long-term distant metastasis free survival (DMFS) for the patients with a low- and a high risk 70-gene signature (DMFS p.0001), as well as separately for node-negative (DMFS p<0.0001) and node positive patients (DMFS p = 0.0004). The 25-year hazard ratios (HRs) for all patients for DMFS and OS were 3.1 (95 % CI 2.02–4.86) and 2.9 (95 % CI 1.90–4.28), respectively. The HRs for DMFS and OS were largest in the first 5 years after diagnosis: 9.6 (95 % CI 4.2–22.1) and 11.3 (95 % CI 3.5–36.4), respectively. The 25-year HRs in the subgroup of node-negative patients for DMFS and OS were 4.57 (95 % CI 2.31–9.04) and 4.73 (95 % CI 2.46–9.07), respectively, and for node-positive patients for DMFS and OS were 2.24 (95 % CI 1.25–4.00) and 1.83 (95 % CI 1.07–3.11), respectively. The 70-gene signature remains prognostic at longer follow-up in patients53 years of age with stage I and II breast cancer. The 70-gene signature’s strongest prognostic power is seen in the first 5 years after diagnosis. See article.