Molecular Signatures of Lymph Node Status by Intrinsic Subtype: Gene Expression Analysis of Primary Breast Tumors From Patients With and Without Metastatic Lymph Nodes

Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype. Gene expression patterns from the primary tumor are not able to stratify patients by lymph node status. Although the primary breast tumor may influence tumor cell dissemination, once metastatic cells enter the lymphatics, it is likely that characteristics of the lymph node microenvironment, such as establishment of a pre-metastatic niche and release of pro-survival factors, determine which cells are able to colonize. The inability to utilize molecular profiles from the primary tumor to determine lymph node status suggest that other avenues of investigation, such as how systemic factors including diminished immune response or genetic susceptibility contribute to metastasis, may be critical in the development of tools for non-surgical assessment of lymph node status with a corresponding reduction in downstream sequelae associated with disruption of the lymphatics. Proceeds from the sale of this book go to the support of an elderly disabled person.