A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
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Springer Nature
2018
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| Online Access: | http://hdl.handle.net/1721.1/117018 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1811069349103927296 |
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| author | Sparano, Joseph A. Gray, Robert Oktay, Maja H. Entenberg, David Rohan, Thomas Xue, Xiaonan Donovan, Michael Peterson, Michael Shuber, Anthony Hamilton, Douglas A. D’Alfonso, Timothy Goldstein, Lori J. Gertler, Frank Davidson, Nancy E. Condeelis, John Jones, Joan |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sparano, Joseph A. Gray, Robert Oktay, Maja H. Entenberg, David Rohan, Thomas Xue, Xiaonan Donovan, Michael Peterson, Michael Shuber, Anthony Hamilton, Douglas A. D’Alfonso, Timothy Goldstein, Lori J. Gertler, Frank Davidson, Nancy E. Condeelis, John Jones, Joan |
| author_sort | Sparano, Joseph A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:09:42Z |
| format | Article |
| id | mit-1721.1/117018 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:09:42Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1170182022-09-30T07:58:58Z A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer Sparano, Joseph A. Gray, Robert Oktay, Maja H. Entenberg, David Rohan, Thomas Xue, Xiaonan Donovan, Michael Peterson, Michael Shuber, Anthony Hamilton, Douglas A. D’Alfonso, Timothy Goldstein, Lori J. Gertler, Frank Davidson, Nancy E. Condeelis, John Jones, Joan Massachusetts Institute of Technology. Department of Biology Gertler, Frank 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. Breast Cancer Research Foundation 2018-07-19T20:09:46Z 2018-07-19T20:09:46Z 2017-11 2018-06-18T14:34:26Z Article http://purl.org/eprint/type/JournalArticle 2374-4677 http://hdl.handle.net/1721.1/117018 Sparano, Joseph A., et al. “A Metastasis Biomarker (MetaSite Breast™ Score) Is Associated with Distant Recurrence in Hormone Receptor-Positive, HER2-Negative Early-Stage Breast Cancer.” Npj Breast Cancer, vol. 3, no. 1, Dec. 2017. https://orcid.org/0000-0003-3214-4554 http://dx.doi.org/10.1038/S41523-017-0043-5 npj Breast Cancer Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Nature |
| spellingShingle | Sparano, Joseph A. Gray, Robert Oktay, Maja H. Entenberg, David Rohan, Thomas Xue, Xiaonan Donovan, Michael Peterson, Michael Shuber, Anthony Hamilton, Douglas A. D’Alfonso, Timothy Goldstein, Lori J. Gertler, Frank Davidson, Nancy E. Condeelis, John Jones, Joan A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title | A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title_full | A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title_fullStr | A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title_full_unstemmed | A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title_short | A metastasis biomarker (MetaSite Breast™ Score) is associated with distant recurrence in hormone receptor-positive, HER2-negative early-stage breast cancer |
| title_sort | metastasis biomarker metasite breast™ score is associated with distant recurrence in hormone receptor positive her2 negative early stage breast cancer |
| url | http://hdl.handle.net/1721.1/117018 https://orcid.org/0000-0003-3214-4554 |
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