Breast Cancer Spread: A New Test to Predict Metastases

What You Need to Know: A new test (MetaSite Breast) may be commercially available in late 2015. It relies on the tumor microenvironment of metastasis (TMEM) score, something found to be linked to the potential for breast cancer spread (metastasis).

Background: Historically, the most powerful prognosticators for breast cancer included the number of underarm (axillary) nodes involved, size of the primary tumor, and measures of proliferation such as grade. More recent tests for prognosis are based on gene signatures found within the tumors.

Seed and Soil Story: The story of how TMEM fits into the mechanism of tumor metastasis is not a simple one. In their editorial, Dr Jain and colleagues discuss the “seed and soil” theory of metastasis originally proposed by Paget more than 100 years ago, in which the “seed” is a tumor cell, and its ability to thrive depends on the “soil” of the tumor microenvironment. According to the editorial, when the tumor travels to its metastatic site (congenial soil), it carries along with it some of the the original “soil” in which it grew.

Although TMEM is focussed on a trio of cells — tumor cells, macrophages, and endothelial cells lining blood vessels — that are present at the extravasation site, Dr Jain’s editorial indicates that preclinical models of metastasis provide evidence that heterotypic clumps of cells that travel to other sites may additionally contain other cells from the original soil in which it grew — fibroblasts, myeloid cells, and stromal cells.

These observations from animal models suggest that tumor metastasis does not conform to the standard view that “single cancer cells crawl into the blood vessels, adhere downstream to the endothelium, and then transmigrate in a manner similar to leukocytes.”

  • The MetaSite Breast test could be available commercially late next year. It relies on determining the tumor microenvironment of metastasis (TMEM) score, and a group of researchers from the Albert Einstein College of Medicine in New York City have shown that it is possible to correlate this score with the potential for breast cancer metastasis.
  • Tumor microenvironment of metastasis (TMEM), consisting of direct contact between a macrophage, an endothelial cell, and a tumor cell, has been associated with metastasis in both rodent mammary tumors and human breast cancer.

My Take: Currently used gene signatures (including MammaPrint and OncoType DX) are associated with the probability of distant disease recurrence and are in clinical use as prognosticators. These signatures are primarily driven by genes reflecting the amount of cancer cell proliferation and the presence (or absence) or hormone receptors in the tumor. Now we have the exciting promise of adding in characteristics of the tumor microenvironment to offer better prognoses. I think this approach represents a fundamental change in how we approach cancer. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.


  • Thomas E. Rohan, et al. JNCI J Natl Cancer Inst Volume 106, Issue 8
  • Solicited editorial: Dan G. Duda, Marek Ancukiewicz, Steven J. Isakoff, Ian E. Krop, Rakesh K. Jain. July 31, 2014.

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Harvard AB Yale MD UPenn Radiation Oncology Radiation Oncologist, Seattle area

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