Publication

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

Journal Paper/Review - Nov 16, 2010

Units
PubMed
Doi

Citation
Knauer M, Cardoso F, Wesseling J, Bedard P, Linn S, Rutgers E, van 't Veer L. Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature. Br J Cancer 2010; 103:1788-93.
Type
Journal Paper/Review (English)
Journal
Br J Cancer 2010; 103
Publication Date
Nov 16, 2010
Issn Electronic
1532-1827
Pages
1788-93
Brief description/objective

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.