Validation of 70-gene prognosis signature in node-negative breast cancer

Abstract

International audienceThe 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530–536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer ( = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999–2009, 2002; = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2–9.6; = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6–20; = 0.007). In the updated series ( = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9–30; < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5–12; < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

“…The prognostic value of 70-gene profile has been validated in a range of series of patients [3][4][5][6]. These studies confirmed that the 70-gene signature accurately discriminates between patients at high risk of distant metastasis and death and patients with a favorable prognosis.…”

Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study

“…8,13,[22][23][24][25] Evidence supporting the predictive value of the 70-GS on CT benefit is limited; therefore, its clinical utility mainly lies in its prognostic capacity. [26][27][28] Currently, the MINDACT trial is being conducted and the first results are expected by the end of this calendar year, which will further assess the predictive capacity of the 70-GS in a randomized prospective setting.…”

The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer

“…The 70-gene signature, which is being performed on fresh (frozen) tumor tissue, has shown to have a strong prognostic power for early breast cancer patients [5,6,13,14]. The 70-gene set was developed using the so-called data-driven approach, i.e., without a priori knowledge of the role of the involved genes, whereas for example the 21-gene RS used the knowledge-driven approach, i.e., genes known to be involved in breast cancer formation and metastatic spreading were included.…”