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Towards a new “stromal-based” classification system for human breast cancer prognosis and therapy

Agnieszka K. Witkiewicz, Mathew C. Casimiro, Abhijit Dasgupta, Isabelle Mercier, Chenguang Wang, Gloria Bonuccelli, Jean-François Jasmin, Philippe G. Frank, Richard G. Pestell, Celina G. Kleer, Federica Sotgia and Michael P. Lisanti

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Here, we discuss recent evidence that an absence of stromal Cav-1 expression in human breast cancers is a powerful single independent predictor of early disease recurrence, metastasis, and poor clinical outcome. These findings have now been validated in two independent patient populations. Importantly, the predictive value of stromal Cav-1 is independent of epithelial marker status, making stromal Cav-1 a new “universal” or “widely-applicable” breast cancer prognostic marker. We propose based on the expression of stromal Cav-1, that breast cancer patients could be stratified into high-risk and low-risk groups. High-risk patients showing an absence of stromal Cav-1 should be offered more aggressive therapies, such as anti-angiogenic approaches, in addition to the standard therapy regimens. Mechanistically, loss of stromal Cav-1 is a surrogate biomarker for increased cell cycle progression, growth factor secretion, “stemness”, and angiogenic potential in the tumor microenvironment. Since almost all cancers develop within the context of a stromal microenvironment, this new stromal classification system may be broadly applicable to other epithelial and non-epithelial cancer subtypes, as well as “pre-malignant” lesions (carcinoma in situ).

Authors

Agnieszka K. Witkiewicz

Thomas Jefferson University; Philadelphia, PA

Mathew C. Casimiro

Thomas Jefferson University; Philadelphia, PA

Abhijit Dasgupta

Thomas Jefferson University; Philadelphia, PA

Isabelle Mercier

Thomas Jefferson University; Philadelphia, PA

Chenguang Wang

Thomas Jefferson University; Philadelphia, PA

Gloria Bonuccelli

Thomas Jefferson University; Philadelphia, PA

Jean-François Jasmin

Thomas Jefferson University; Philadelphia, PA

Philippe G. Frank

Thomas Jefferson University; Philadelphia, PA

Richard G. Pestell

Thomas Jefferson University; Philadelphia, PA

Celina G. Kleer

University of Michigan Medical School; Ann Arbor, Michigan

Federica Sotgia

Thomas Jefferson University; Philadelphia, PA

Michael P. Lisanti Corresponding author: michael.lisanti@kimmelcancercenter.org

Thomas Jefferson University; Philadelphia, PA

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.