Subpopulations of tumor cells can form microanatomic associations with endothelial cells and macrophages termed “tumor microenvironments of metastasis” (TMEM), which facilitate penetration of blood vessels and, consequently, distant spread.

First identified in mice, these TMEM “MetaSites” have also been identified in human early-stage breast cancers, and MetaSite Scores (MS) represent a novel biomarker of metastasis, according to clinical-validation research presented at the 2016 San Antonio Breast Cancer Symposium.1

TMEMs are “the doorway for metastasis,” said Joseph A. Sparano, MD, of the Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

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“This is the third study showing an association with recurrence,” Dr Sparano said. “MS is prognostic independent of tumor size, grade, nodal status, and [Oncotype DX] Recurrence Score in HR-positive, HER2-negative disease. MS is prognostic for early recurrence within 5 years.”

Analyzing tumors from 600 patients with early-stage breast cancers who had undergone surgery, adjuvant chemotherapy, and endocrine therapy, MS were assigned using a “fully automated digital pathology image analysis” algorithm.

MS was associated with distant relapse-free interval (DFRI) and relapse free interval (RFI), Dr Sparano reported. MetaSite and Oncotype DX Recurrence were modestly associated.

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“Tumor size and lymph node metastases are time-dependent prognostic factors,” Dr Sparano said. The risk of metastasis is a function of those 2 factors, treatment sensitivity (Recurrence Score), and risk of dissemination (the MetaSite score), Dr Sparano said.

“Further evaluation is warranted in order to identify patients at highest risk of recurrence within 5 years who are most likely to benefit from adjuvant chemotherapy or novel therapies,” he concluded.


  1. Sparano JA, Gray R, Oktay MH, et al. Tumor microenvironment of metastasis (TMEM) score is associated with early distant recurrence in hormone receptor (HR) positive, HER2-negative early stage breast cancer (ESBC) Paper presented at: 39th San Antonio Breast Cancer Symposium; Dec 2016; San Antonio, TX.