Abstract P4-07-32: Mammaprint and Blueprint are prognostic of outcome following neoadjuvant chemotherapy
Authors: Chung Alice P. , Srour Marissa , Dadmanesh Farnaz , Kim Sungjin , Giuliano Armando , Wei Jennifer , Huynh Yen , Wang Shiyu , Menicucci Andrea , Audeh William 
Published: March 2022

Abstract
Introduction: Neoadjuvant chemotherapy (NAC) is used increasingly in patients with early-stage breast cancer (EBC). Genomic approaches are necessary to identify better biomarkers that can more accurately predict response to NAC and outcome. The impact of NAC on the molecular biology of breast tumors, especially in patients that fail to respond to treatment, is not well studied. We evaluated the risk of distant recurrence signature, MammaPrint (MP), and the molecular subtyping signature, BluePrint (BP), in the neoadjuvant setting and how the prognostic capability of MP and BP, which was validated on untreated biopsies, is affected by NAC in patients with residual disease. Methods: This analysis included 128 women (median age 50) with stage I-III EBC, of any clinical subtype, diagnosed from 2007-2016 who received NAC at Cedars-Sinai Medical Center. Of 128 patients, 73 had core needle biopsies available before treatment, 17 had surgically resected biopsies with residual disease available after treatment, and 38 with residual disease had paired pre- and post-treatment biopsies. MP classified tumors as High Risk (MP-HR) or Low Risk (MP-LR). MP and BP classified tumors as Luminal A (MP-LR), Luminal B (MP-HR), HER2, or Basal. The primary outcomes were pathological complete response (pCR), recurrence free survival (RFS), distant-metastasis free survival (DMFS), and overall survival (OS). The median follow-up time was 5.2 years. Differences between unmatched independent variables were examined by chi-square test or Fisher’s exact test. Differences in pCR rate were assessed by two-sided proportional z-test. For matched samples, McNemar’s test or Bowker’s test was used. Univariate survival analyses were evaluated using a Cox proportional hazards model. Results: Among 111 pre-treated tumors, MP-HR tumors had a significantly higher pCR rate (40.6%; n=39/96) compared to MP-LR tumors (13.3%; n=2/15; p=0.042). BP HER2 and Basal tumors had significantly higher pCR rates (56.8%; n=25/44 and 45.8%; n=11/24, respectively), compared to Luminal B tumors (16.1%; n=5/31; p&lt;0.001 and p = 0.016 respectively). No Luminal A tumors (n=12) achieved pCR. MP-HR and BP Basal tumors were associated with a higher risk of recurrence or death than MP-LR and Luminal tumors. Among all 128 tumors, post-treated samples were more likely to be classified as MP-LR than pre-treated samples (45.5%; n=25/55 vs. 13.5%; n=15/111), whereas BP subtype distribution was similar. Among 38 paired samples with residual disease, BP subtype did not significantly differ after NAC (p=0.392) and had 92% concordance between pre- and post-treated samples. Basal tumors, whether classified before or after NAC was significantly associated with a RFS (HR=4.79, 95% CI 1.09-20.97; p=0.038), DMFS (HR=4.86, 95% CI 1.28-18.64; p=0.018), or OS event (HR=22.03, 95% CI 2.41-201.26; p=0.006) compared to luminal tumors. A significant number (26%; n=10; p=0.002) of tumors had discordant MP risk between pre- and post-treatment samples, all of which reclassified from MP-HR (Luminal B) to MP-LR (Luminal A). MP-HR tumors that reclassified as MP-LR after NAC had better 5-year OS (100%) compared to tumors that remained MP-HR (73.3%, 95% CI 47.2 - 87.9). Conclusions: MP and BP accurately predicted chemosensitivity and outcomes in NAC treated patients. Activated molecular pathways captured by BP classification remained stable after NAC treatment, with a high concordance rate. Approximately 1 out of 4 Luminal B (MP-HR) tumors reclassified as Luminal A (MP-LR) after NAC and have improved 5-year outcome compared to tumors that remained MP-HR. Together, this preliminary evidence supports the prognostic accuracy of MP and BP on tumors following NAC treatment. Future studies will study the effect of NAC on the BC transcriptome and their association with clinical outcomes.
Citation Format: Alice P. Chung, Marissa Srour, Farnaz Dadmanesh, Sungjin Kim, Armando Giuliano, Jennifer Wei, Yen Huynh, Shiyu Wang, Andrea Menicucci, William Audeh. Mammaprint and Blueprint are prognostic of outcome following neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-32.