The majority of breast cancer cases diagnosed in western countries are hormone receptor positive. Front line treatment for advanced ER+ breast cancer has changed over the last few years with combination therapies that add to antiestrogen agents a CDK 4/6 inhibitor (cyclin dependent kinase).
The first combination therapy FDA approved was fulvestrant with pablociclib (Ibrance). This therapy revealed a better response rate, which exceeded 40%, and disease-free survival compared to single agent therapy.
The addition of CDK 4/6 inhibitors helps overcome endocrine resistance. Palbociclib and letrozole verses letrozole alone revealed a response rate of 55% versus 44% and disease-free survival 24 months versus 14 for the combination versus single agent.
The CDK 4/6 inhibitors can cause neutropenia although milder than with chemotherapy and usually not associated with infections.
Ribociclib is the next CDK 4/6 inhibitor. Recently FDA approved in combination with letrozole (aromatase inhibitor) with disease-free survival at 18 months of 63% compared to 42% with single agent, and a response rate of 52% compared to 37% with single agent.
Another class of drugs that helps overcome endocrine resistance is the mTOR inhibitors (mammalian) target of rapamycin inhibitors. The mTOR pathway is upregulated in breast cancer promoting growth and the inhibition promotes tumor response to therapy.
The mTOR inhibitor everolimus was combined with examestane versus examestane single agent and the combination therapy had a median disease free survival of 10.6 months versus four months for single agent. The median overall survival was 31 months for the combination treatment versus 26 months for single agent treatment.