Abstract
BACKGROUND: Neoadjuvant chemotherapy (NCT) increases the feasibility of surgical resection by downstaging large primary breast tumors and nodal involvement, which may result in surgical de-escalation and improved outcomes. This subanalysis from the Multi-Institutional Neo-adjuvant Therapy MammaPrint Project I (MINT) trial evaluated the association between MammaPrint and BluePrint with nodal downstaging. PATIENTS AND METHODS: The prospective MINT trial (NCT01501487) enrolled 387 patients between 2011 and 2016 aged ≥ 18 years with invasive breast cancer (T2-T4). This subanalysis includes 146 patients with stage II-III, lymph node positive, who received NCT. MammaPrint stratifies tumors as having a Low Risk or High Risk of distant metastasis. Together with MammaPrint, BluePrint genomically (g) categorizes tumors as gLuminal A, gLuminal B, gHER2, or gBasal. RESULTS: Overall, 45.2% (n = 66/146) of patients had complete nodal downstaging, of whom 60.6% (n = 40/66) achieved a pathologic complete response. MammaPrint and combined MammaPrint and BluePrint were significantly associated with nodal downstaging (p = 0.007 and p < 0.001, respectively). A greater proportion of patients with MammaPrint High Risk tumors had nodal downstaging compared with Low Risk (p = 0.007). When classified with MammaPrint and BluePrint, more patients with gLuminal B, gHER2, and gBasal tumors had nodal downstaging compared with HR+HER2-, gLuminal A tumors (p = 0.538, p < 0.001, and p = 0.013, respectively). CONCLUSIONS: Patients with genomically High Risk tumors, defined by MammaPrint with or without BluePrint, respond better to NCT and have a higher likelihood of nodal downstaging compared with patients with gLuminal A tumors. These genomic signatures can be used to select node-positive patients who are more likely to have nodal downstaging and avoid invasive surgical procedures.