Abstract PS6-30: Combined use of MammaPrint and BluePrint assays to evaluate patients for response to neo-adjuvant chemotherapy for locally advanced breast cancer

Abstract

Abstract Background: The main goal of the Multi-Institutional Neo-Adjuvant Therapy MammaPrint (MINT) project was to determine the predictive power of the combination of the molecular assays MammaPrint and BluePrint (Agendia Inc., Irvine, CA) for chemosensitivity as measured by complete pathological response (pCR) in patients with locally advanced breast cancer (LABC). MammaPrint is a 70-gene microarray-based assay that classifies each breast cancer patient as low or high risk to develop metastases within 10 years after diagnosis. The BluePrint test is an 80-gene molecular subtyping profile that discriminates between luminal, basal and HER-2 subtypes. Methods: After appropriate IRB approval, 270 female patients with histologically-proven invasive breast cancer and no distant metastases were enrolled in this study. Patients had a clinical tumor classification of T2-T4 with 0-3 positive lymph nodes. DCIS or LCIS was allowed in addition to invasive cancer at the T2 or T3 levels. At least one lesion had to be accurately measured in two dimensions utilizing mammogram, ultrasound, or MRI images to define specific size and validate pCR. Patients were required to have adequate bone marrow reserves, renal function and hepatic function, as determined by standard blood and serum measurements. Patients under 18 years of age or those with confirmed metastatic disease, inflammatory breast cancer, any serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease were excluded. Patients with any prior chemotherapy, radiotherapy, or endocrine therapy for the treatment of breast cancer were also excluded. Tumor samples were collected via incisional or core needle biopsy and shipped to Agendia for processing of the MammaPrint and BluePrint gene panels, as well as whole human genome expression microarrays. Comparison of response rates between MammaPrint and BluePrint molecular subtypes was conducted using Pearson Chi-square test with chemo-responsiveness measured as a binary response: pCR or residual disease. Results: Of 270 patients enrolled, 56 did not have TNM or RCB staging information reported in the case report form and/or were not submitted for central pathology review. Of 214 patients evaluated by central pathology review, 68 (32%) exhibited a pCR. Patients with a high risk MammaPrint result had a higher pCR rate (37%) compared to patients with a low risk MammaPrint (0%). And patients with a HER-2 or basal molecular subtype by BluePrint had significantly higher rates of pCR (62%, 37%, respectively). Conclusion: Upfront evaluation of LABC tumors using the combination of MammaPrint and BluePrint can help in the clinico-pathologic evaluation to determine which patients are more likely to benefit from neo-adjuvant chemotherapy, ranging from expected minimal response in Luminal A to substantial responses for HER2-type and Basal-type tumors. Additional studies to evaluate the prognostic and/or predictive values of additional gene panels from the whole human genome microarrays are underway. Rate of pCR in MammaPrint and MammaPrint/BluePrint groupsGroupsResidual DiseasepCRP valueMP Risk GroupLow Risk27 (100%)0 (0%)0.0004High Risk114 (63%)67 (37%)BP subtypeBasal42 (63%)25 (37%)2 x 10-9HER220 (38%)33 (62%)Luminal A26 (100%)0 (0%)Luminal B53 (85%)9 (15%) Citation Format: Brian Longbottom, Steven C Shivers, Geza Acs, Charles E Cox. Combined use of MammaPrint and BluePrint assays to evaluate patients for response to neo-adjuvant chemotherapy for locally advanced breast cancer [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 PS6-30.