Strong time-dependency of the
76-gene prognostic signature for node-negative breast cancer patients
in the TRANSBIG multi-centre independent validation series.
Desmedt
C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G,
Delorenzi M, Zhang Y, Saghatchian d’Assignies M, Bergh J, Lidereau R,
Ellis P, Harris A, Klijn JG, Foekens JA, Cardoso F, Piccart MJ, Buyse M
and Sotiriou C
Background: Recently
a 76-gene prognostic signature able to predict distant metastases in
lymph node-negative (N-) breast cancer patients was reported. The aims
of this study conducted by TRANSBIG were to independently validate
these results and to compare the outcome with clinical risk assessment.
Materials and Methods:
Gene expression profiling of frozen samples from 198 N- systemically
untreated patients was performed at the Bordet Institute, blinded to
clinical data and independent of Veridex. Genomic risk was defined by
Veridex, blinded to clinical data. Survival analyses, done by an
independent statistician, were performed with the genomic risk and
adjusted for the clinical risk, defined by Adjuvant!Online.
Results:
The actual 5- and 10-year time to distant metastasis (TDM) were 98%
(88%-100%) and 94% (83%-98%) respectively for the good profile group
and 76% (68%- 82%) and 73% (65%-79%) for the poor profile group. The
actual 5- and 10-year overall survival (OS) were 98% (88%-100%) and 87%
(73%-94%) respectively for the good profile group and 84% (77%-89%) and
72% (63%-78%) for the poor profile group. We observed a strong
time-dependency of this signature, leading to an adjusted HR of 13.58
(1.85-99.63) and 8.20 (1.10-60.90) at 5 years, and 5.11 (1.57-16.67)
and 2.55 (1.07-6.10) at 10 years for TDM and OS respectively.
Conclusion:
This independent validation confirmed the performance of the 76-gene
signature and adds to the growing evidence that gene expression
signatures are of clinical relevance, especially for identifying
patients at high risk of early distant metastases.