Apple falls far from the tree.

Top Line: “These observations provide substance to the conviction that positive axillary lymph nodes are not the predecessor of distant tumor spread but represent one manifestation of disseminated disease.” 
The Study: Bernard Fisher wrote that in 1977 in the initial publication of the B-04 trial. The near centenarian probably chuckles that this idea continues to be debated more than 40 years later. While our understanding of the molecular underpinnings of breast cancer has grown, our comprehension of its molecular evolution remains limited. In the current study, extensive genomic sequencing of patient, primary tumor, nodal tumor, and circulating tumor DNA was performed on treatment naive women with breast cancer metastatic to the nodes. The big conclusion? Linear evolution is rare. Think of linear evolution like the classic diagram of ape to neanderthal to modern human. With cancer, this classic picture includes tumor formation, stepwise transitions through the hallmarks of cancer, and eventually subpopulations with the ability to spread to lymph nodes. In reality, about half of these breast cancers showed early genetic divergence while the other half showed almost no divergence. With early divergence, the nodal mets and the primary tumor have almost nothing in common (genetically speaking). Nodal mets arise very early in tumorigenesis, part ways, and do their own thing. Even more interesting, the majority of circulating tumor DNA actually came from the nodes and not the primary tumor. For the other "classic" tumors with no divergence, the nodes and primary tumor are extremely similar and probably do follow some slow stepwise progression.
Bottom Line: In many node positive breast cancers, lymph node metastases arise early in tumorigenesis and harbor molecular changes completely distinct from primary tumors. | Barry, Clin Cancer Res 2018


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