Abstract PD9-01: 5-year outcomes in the NBRST trial: Preoperative MammaPrint and BluePrint breast cancer subtype is associated with neoadjuvant treatment response and survival
Authors: Pat Whitworth, James V Pellicane, Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Erin B Yoder, Andrea Menicucci, Lisa Blumencranz, William Audeh
Journal: Cancer Research (2021)

Abstract Background: MammaPrint (MP) is used to identify breast cancer (BC) patients who can safely forego adjuvant chemotherapy. MP combined with the BluePrint (BP) molecular subtyping signature identifies BC subtypes with distinct therapeutic response rates and survival outcomes. In the Neoadjuvant Breast Symphony Trial (NBRST), MP and BP (MP/BP) predicted rates of pathologic complete response to neoadjuvant chemotherapy (NCT) and partial response to neoadjuvant endocrine therapy (NET). Here, we report 5-year overall survival (OS) and distant metastasis-free survival (DMFS) in patients from the NBRST registry according to MP/BP molecular classification. Methods: The NBRST trial (NCT01479101) prospectively enrolled 1072 patients from 2011 to 2014, who received MP and BP testing. Patients were assigned to receive NCT or NET according to NCCN guidelines and consented to 5 years post-surgery follow-up (FU). Clinical outcomes were available for 913 patients from 67 US institutions. Median FU for OS and DMFS was 5 and 4.6 years, respectively. Tumors classified by MP as High Risk (HR) or Low Risk (LR) were further stratified into four molecular subtypes by BP: Luminal A, Luminal B, HER2, and Basal. Differences in OS and DMFS at 3 and 5 years were assessed by Kaplan Meier analysis and log-rank test. Results: MP results from neoadjuvant patients (N=913) classified 16% of tumors as MP LR and 84% as MP HR. MP and BP classified 15.7% (143/913) of tumors as Luminal A, 32.5% (297/913) as Luminal B, 17.1% (156/913) as HER2, and 34.7% (317/913) as Basal. The 5-year OS and DMFS probabilities were significantly lower in HR compared to LR patients (p &amp;lt; 0.001 for OS and DMFS), and lowest in Basal and Luminal B compared to Luminal A and HER2 subtypes (p &amp;lt; 0.001 for OS and DMFS). Most DMFS events in BP Basal tumors occurred within the first 3 years. Of 841 patients that received NCT with or without HER2-targeted therapy, 12.2% (103/841) were LR and 87.8% (738/841) were HR. MP and BP classified 11.9% (100/841) of these patients as Luminal A, 32.6% (274/841) as Luminal B, 8.3% (154/841) as HER2 subtype, and 37.2% (313/841) as Basal. The 5-year OS and DMFS probabilities were lowest in HR, Basal or Luminal B patients (p &amp;lt; 0.001). In 59 patients who received NET alone, 5-year OS and DMFS were significantly worse in HR patients that had Luminal B or HER2 tumors compared to LR Luminal A patients. In the 39 patients with Luminal A tumors, response to NET at the time of surgery was: 46.2% partial response, 41.0% stable disease, 5.1% progressive disease, 2.6% not reported. Five year DMFS in patients with Luminal A tumors treated with NCT or NET was not significantly different (p=0.67).Conclusions: MammaPrint remained prognostic in BC patients undergoing neoadjuvant therapy. Long -term prognosis was excellent in LR groups who received NCT or NET alone. MP and BP can accurately classify patients into specific subtypes with distinct OS and DMFS outcomes at five years, with BP Basals having the worst outcomes, followed by Luminal B, HER2, and Luminal A subtypes. BP Basal patients had the highest frequency of events within the first 3 years post-surgery, suggesting a genomic risk timeline distinct from other BP subtypes and a potential benefit from a secondary therapeutic immediately post-surgery. Additionally, Luminal A patients had a very low risk of progressive disease while on NET alone prior to surgery, with similar DMFS outcomes to Luminal A-types who received NCT. Number of patientsObserved events% at 5 year (95% CI)p-valueAll patients - MammaPrint Risk GroupOS913134p&amp;lt;0.001Low Risk146794.7 (88.4-97.6)High Risk76712781.1 (77.7-84.0)DMFS913182p&amp;lt;0.001Low Risk1461191.2 (84.2-95.2)High Risk76717175.5 (71.9-78.7)All patients - MammaPrint + BluePrint SubtypeOS913134p&amp;lt;0.001Luminal A143794.6 (88.3-97.6)Luminal B2974484.5 (80.0-88.7)Basal3177472.2 (66.2-77.3)HER2156993.4 (87.1-96.7)DMFS913182p&amp;lt;0.001Luminal A1431191.1 (82.1-94.3)Luminal B2976975.2 (68.0-80.4)Basal3178570.4 (64.6-75.5)HER21561787.2 (79.7-92.0)NCT patients - MammaPrint Risk GroupOS841121p&amp;lt;0.001Low Risk103397.4 (90.1-99.4)High Risk73811881.7 (78.3-84.7)DMFS841167p&amp;lt;0.001Low Risk103792.6 (84.1-96.6)High Risk73816076.2 (72.5-79.4)NCT patients - MammaPrint + BluePrint SubtypeOS841121p&amp;lt;0.001Luminal A100395.5 (86.2-98.6)Luminal B2743978.9 (71.7-84.5)Basal3137168.7 (57.9-77.2)HER2154892.8 (85.9-96.4)DMFS841167p&amp;lt;0.001Luminal A100792.4 (83.8-96.5)Luminal B2746375.7 (65.6-76.5)Basal3138171.4 (65.6-76.5)HER21541687.7 (80.2-92.5)NET alone patients - MammaPrintOS597p=0.01Low Risk39293.0 (74.6-98.2)High Risk20580.0 (55.1-92.0)DMFS598p=0.003Low Risk39293.0 (74.6-98.2)High Risk20674.7 (49.4-88.6)NET alone patients - MammaPrint +BluePrint SubtypeOS597p=0.008Luminal A39293.0 (74.6-98.2)Luminal B18483.3 (56.8-94.3)Basal00N/AHER221N/ADMFS598p=0.005Luminal A39293.0 (74.6-98.2)Luminal B18577.4 (50.3-90.9)Basal00N/AHER221N/A Citation Format: Pat Whitworth, James V Pellicane, Jr., Paul Baron, Peter Beitsch, Laura Lee, Michael Rotkis, Angela Mislowsky, Carrie Dul, Charles Nash, Bichlien Nguyen, Mary Murray, Paul Richards, Mark Gittleman, Stephanie Akbari, Shiyu Wang, Erin B Yoder, Andrea Menicucci, Lisa Blumencranz, William Audeh, NBRST Investigators Group. 5-year outcomes in the NBRST trial: Preoperative MammaPrint and BluePrint breast cancer subtype is associated with neoadjuvant treatment response and survival [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-01.