Paradox CA 15-3 increase in metastatic breast cancer patients treated with everolimus: a change of paradigm in a case series.

Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15-3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15-3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth. Vice versa, the block of this pathway may influence MUC-1 expression and CA 15-3 serum levels. In this report, we emphasize the equivocal role of CA 15-3 serum levels in monitoring treatment with everolimus, suggesting a potential and intriguing role of a CA 15-3 increase as paradox predictive biomarker of response to everolimus.