Table 1.

Possible hypotheses for mechanism of aromatase inhibitor‐resistant breast cancer

Hypothesis	Possible therapy
1. Promoted metabolism or excretion of the employed AI	Switching to another AI or SERM therapy
2. Structural or qualitative change of aromatase
3. Ligand dependency on other than estrogen   • Androgen metabolites act as a ligand	SERM therapy
4. ER activation via phosphorylation cascade independent of ligands   • Activated growth factor signaling pathways	SERM therapy or combination of SERM and kinase inhibitor
5. Acquired growth ability independent of ER   • ER positive but sensitivity completely lost   • ER negative	Chemotherapy or other molecular targeting therapy

AI, aromatase inhibitor; ER, estrogen receptor; SERM, selective estrogen receptor modulator.