TY - JOUR
T1 - A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptorpositive, HER2-negative early-stage breast cancer
AU - Sparano, Joseph A.
AU - Gray, Robert
AU - Oktay, Maja H.
AU - Entenberg, David
AU - Rohan, Thomas
AU - Xue, Xiaonan
AU - Donovan, Michael
AU - Peterson, Michael
AU - Shuber, Anthony
AU - Hamilton, Douglas A.
AU - D’alfonso, Timothy
AU - Goldstein, Lori J.
AU - Gertler, Frank
AU - Davidson, Nancy E.
AU - Condeelis, John
AU - Jones, Joan
N1 - Funding Information:
We thank Michael Balco and other staff members at the ECOG-ACRIN Central Biospecimen and Pathology Facility at the MD Anderson Cancer Center, Houston, TX. This manuscript was presented on December 8, 2016 at the AACR San Antonio Breast Cancer Symposium,San Antonio, TX. Supported in part by grants from the Department of Health and Human Services and the National Institutes of Health (CA23318 and CA180794 to the ECOG statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center, CA25224 to NCCTG, CA32291 to CALGB, CA32012 to SWOG, and CA100324 and 1S10OD01996 to the Integrated Imaging Program at the Albert Einstein College of Medicine), and by a grant from the Breast Cancer Research Foundation.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/9/6
Y1 - 2017/9/6
N2 - Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call “Tumor Microenviroment of Metastasis” (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I–III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease. TMEM were identified and enumerated using an analytically validated, fully automated digital pathology/image analysis method (MetaSite Breast™), hereafter referred to as MetaSite Score (MS). The objectives were to determine the association between MS and distant relapse free interval (DRFI) and relapse free interval (RFI). MS was not associated with tumor size or nodal status, and correlated poorly with Oncotype DX Recurrence Score (r = 0.29) in 297 patients with HR+/HER2-disease. Proportional hazards models revealed a significant positive association between continuous MS and DRFI (p = 0.001) and RFI (p = 0.00006) in HR+/HER2-disease in years 0–5, and by MS tertiles for DRFI (p = 0.04) and RFI (p = 0.01), but not after year 5 or in triple negative or HER2+ disease. Multivariate models in HR+/HER-disease including continuous MS, clinical covariates, and categorical Recurrence Score (<18, 18–30, > 30) showed MS is an independent predictor for 5-year RFI (p = 0.05). MetaSite Score provides prognostic information for early recurrence complementary to clinicopathologic features and Recurrence Score.
AB - Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call “Tumor Microenviroment of Metastasis” (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I–III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease. TMEM were identified and enumerated using an analytically validated, fully automated digital pathology/image analysis method (MetaSite Breast™), hereafter referred to as MetaSite Score (MS). The objectives were to determine the association between MS and distant relapse free interval (DRFI) and relapse free interval (RFI). MS was not associated with tumor size or nodal status, and correlated poorly with Oncotype DX Recurrence Score (r = 0.29) in 297 patients with HR+/HER2-disease. Proportional hazards models revealed a significant positive association between continuous MS and DRFI (p = 0.001) and RFI (p = 0.00006) in HR+/HER2-disease in years 0–5, and by MS tertiles for DRFI (p = 0.04) and RFI (p = 0.01), but not after year 5 or in triple negative or HER2+ disease. Multivariate models in HR+/HER-disease including continuous MS, clinical covariates, and categorical Recurrence Score (<18, 18–30, > 30) showed MS is an independent predictor for 5-year RFI (p = 0.05). MetaSite Score provides prognostic information for early recurrence complementary to clinicopathologic features and Recurrence Score.
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U2 - 10.1038/S41523-017-0043-5
DO - 10.1038/S41523-017-0043-5
M3 - Article
AN - SCOPUS:85046582122
SN - 2374-4677
VL - 3
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 42
ER -
