Treatment response and 5-year distant metastasis-free survival outcome in breast cancer patients after the use of MammaPrint and BluePrint to guide preoperative systemic treatment decisions.

Aim: In the prospective neoadjuvant NBREaST II study, we measured the response to preoperative treatment and 5-year survival outcome in the molecular subgroups as determined by combining the MammaPrint and BluePrint.

Methods: Between 2012 and 2016 we included 256 patients for whom MammaPrint and BluePrint were performed on pre-treatment core needle biopsies. The primary objective of the NBREaST II trial was to measure chemosensitivity or endocrine sensitivity in the molecular subgroups. Distant metastasis-free survival (DMFS), relapse-free survival (RFS) and breast cancer-specific survival (BCSS) were the endpoints for long-term follow-up.

Results: MammaPrint and BluePrint molecular sub-typing reclassified 9% (24/256) of tumours, reassigning more responsive patients to the HER2-Type and Basal-Type, and less responsive patients to the Luminal-Type category. Patients with Luminal A-Type tumours (n = 67, 26% of the total cohort) had a poor response when treated with neoadjuvant chemotherapy (NCT), but had the highest 5-year DMFS outcome (91.4%; 95% CI 78.6-96.7) of all molecular subgroups. Out of the IHC/FISH defined HER2+ tumours (n = 41), 37% were not classified as HER2-Type by BluePrint. Notably, in BluePrint HER2-Type tumours, we observed a higher pCR rate, whereas the 5-year DMFS was lower compared to IHC/FISH-defined HER2+ tumours. The pCR rate and 5-year outcome for patients with Basal-Type tumours were similar to IHC/FISH-defined TN tumours.

Conclusion: These findings suggest that MammaPrint and BluePrint can predict chemosensitivity and 5-year outcomes more accurately compared to traditional pathological sub-typing, supporting informed decision-making.