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

Publication Name: British Journal of Cancer

Author(s): M Knauer, F Cardoso, J Wesseling, PL Bedard, SC Linn, EJT Rutgers, and LJ van 't Veer

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, P¼0.04) and 3.8 (95% CI 0.9–15.8, P¼0.07) 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, P¼0.03) and 4.7 (95% CI 1.0–21.7, P¼0.05) 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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