Early determination of metastatic potential in breast cancer: The 70-gene signature in small tumors

Abstract

518 Background: Small breast cancers are often considered as low risk tumors in clinico-pathologic risk assessment and treatment guidelines. However, since the ability to metastasize is an early and inherent genetic property of breast cancer and consequently even small tumors can metastasize, identification of prognostic subgroups for patients with small tumors would help to optimize treatment strategies. In the present study the 70-gene prognosis signature (MammaPrint), validated as independent prognostic indicator for node-negative and positive patients, was used to assess prognosis for pT1 breast cancer. Methods: 965 tumor samples of women with pT1 breast cancer from 7 previously reported studies were analyzed and classified by MammaPrint as good or poor prognosis. 10-year distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) was analyzed according to the 70-gene prognosis signature separately for pT1a/b (1–10mm) and pT1c (11–20mm) tumors. Results: Median follow-up was 7.1 years (range 0.2–25.2). 526 of 965 patients (55%) were classified as good prognosis and 439 (45%) as poor prognosis by the 70-gene signature. 562 patients (59%) received no adjuvant treatment, 19% received hormonal treatment only, 10% chemotherapy only and 12% both respectively. The 70-gene signature accurately predicted differences in 10-year DDFS (HR 2.7 [1.9–3.9], p<0.01) and BCSS (HR 4.0 [2.6–6.3], p<0.01) for all T1 tumors. Similar results were obtained by multivariate analysis for all patients, adjusted for known prognostic factors and adjuvant therapy, as well as for adjuvant untreated patients. At 10 years, for small pT1a/b tumors (n=140), DDFS was 93% vs. 78% for the good and poor prognosis groups (HR 3.9 [1.0–15.2], p=0.048), while in the T1c group (n=825) DDFS was 86% vs. 72% (HR 2.6 [1.8–4.0], p<0.01). BCSS was 87% vs. 73% for the good and poor prognosis groups in the T1a/b group (HR 2.4 [0.8–7.7], p=0.128) and 92% vs. 72% (HR 4.4 [2.7–7.1], p<0.01) in T1c tumors, respectively. Conclusions: The 70-gene signature is a strong and independent prognostic indicator also in small breast tumors. Patients with T1a/b or T1c tumors and a genomic high risk gene signature for developing distant metastases may be selected for additional adjuvant hormonal and chemotherapy. [Table: see text]