The Predictive Utility of MammaPrint and BluePrint in Identifying Patients with Locally Advanced Breast Cancer Who are Most Likely to Have Nodal Downstaging and a Pathologic Complete Response After Neoadjuvant Chemotherapy

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.

Keywords: 70-gene signature; 80-gene signature; Axillary staging; Nodal downstaging; Surgical management.

Fig. 1

MINT consort diagram; patients with invasive breast cancer were prospectively enrolled from 2011 to 2016, this subanalysis includes 146 lymph node-positive patients

Fig. 2

Nodal downstaging with neoadjuvant chemotherapy; Sankey diagram depicting the nodal status changes from pre-neoadjuvant chemotherapy (left) to post-neoadjuvant chemotherapy (right)

Fig. 3

Association of nodal downstaging by MammaPrint and BluePrint; (a) MammaPrint Index was plotted for tumors from patients with nodal downstaging (cN+ to ypN0) and compared with residual disease tumors (cN+ to ypN+), (b) proportion of patients with Low Risk tumors having nodal downstaging (ypN0) and residual disease (RD) was compared with those with High Risk tumors, (c) patients were also categorized by BluePrint molecular subtype and MammaPrint Index was plotted for patients with ypN0 or RD for each molecular subtype, for gLuminal A tumors, MammaPrint indices are only shown for HR+HER2− tumors, (d) percentage of patients who achieved nodal downstaging for each BluePrint subtype, proportion of patients with gLuminal B, gHER2, and gBasal tumors who achieved ypN0 were compared with patients with gLuminal A tumors (the frequency of nodal downstaging for gLuminal A is shown for patients with HR+HER2− tumors), (e) within gHER2 and gBasal tumors, the percent of patients with nodal downstaging and residual disease are shown by hormone status, (f) percentage of patients who achieved pCR for each BluePrint subtype, proportion of patients with gLuminal B, gHER2, and gBasal tumors who achieved a pCR were compared with patients with gLuminal A tumors, significance between continuous variables (MammaPrint Index) was assessed using unpaired t-test or one-way ANOVA, two-tailed proportional z-test was used to compare categorical subgroups and between hormone status