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Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature.

  • Author(s): Knauer, M
  • Cardoso, F
  • Wesseling, J
  • Bedard, PL
  • Linn, SC
  • Rutgers, EJT
  • van 't Veer, LJ
  • et al.
Abstract

Background

overexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.

Methods

in all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.

Results

in the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.

Interpretation

the 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome.

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