Vliek, Sonja B., Hilbers, Florentine S., Jager, Agnes, Retèl, Valesca P., Bueno de Mesquita, Jolien M., Drukker, Caroline A., Veltkamp, Sanne C., Zeillemaker, Anneke M., Rutgers, Emiel J., van Tinteren, Harm, van Harten, Wim H., van 't Veer, Laura J., van de Vijver, Marc J., and Linn, Sabine C.
Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited. In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint). The results were provided to their treating physician to be incorporated in the decision-making on adjuvant systemic therapy. Here, we report the long-term outcome of the 310 patients with ER-positive, HER2-negative tumours by clinical and genomic risk categories at a median follow-up of 10.3 years. Among the clinically high-risk patients, 45 (49%) were classified as genomically low risk. In this subgroup, at 10 years, distant recurrence free interval (DRFI) was similar between patients treated with (95.7% [95% CI 87.7–100]) and without (95.5% [95% CI 87.1–100]) chemotherapy. Within the group of clinically low-risk patients, 56 (26%) were classified as genomically high risk. Within the clinically low-risk group, beyond 5 years, a difference emerged between the genomically high- and low-risk subgroup resulting in a 10-year DRFI of 84.3% (95% CI 74.8–95.0) and 93.4% (95% CI 89.5–97.5), respectively. Interestingly, genomic ultralow-risk patients have a 10-year DRFI of 96.7% (95% CI 90.5–100), largely (79%) without systemic therapy. These data confirm that clinically high-risk, genomically low-risk tumours have an excellent outcome in the real-world setting of shared decision-making. Together with the updated results of the MINDACT trial, these data support the use of the MammaPrint, in ER-positive, HER2-negative, node-negative, clinically high-risk breast cancer patients. ISRCTN71917916 • Clinical high-risk, genomic low-risk tumours have similar DRFI with or without chemo. • Genomic ultralow-risk tumours have a good outcome largely without systemic therapy. • 10-year DRFI in clinical low-risk, genomic high-risk tumours suggest undertreatment. [ABSTRACT FROM AUTHOR]