What are the new strategies to overcome resistance to endocrine therapy in breast cancer?

This paper reviewed various strategies of preventing resistance to endocrine therapy. 

Receptors are proteins found on cells that when activated can lead to cell growth and division. Estrogen receptors (protein found on cell) are one such example. Endocrine therapy is given to patients who have breast cancer with the estrogen receptor present. Endocrine therapy works by blocking the activity of estrogen receptor. Endocrine therapy drugs include tamoxifen (Soltamox), aromatase inhibitors (Aromasin, Femara and Arimidex), and fulvestran (Faslodex).  However, resistance to endocrine therapy can develop. 

The authors reported on several studies on various strategies to overcome estrogen resistance.

One strategy combined aromatase inhibitors with trastuzumab (Herceptin). Trastuzumab blocks the activity of human epidermal growth factor receptor 2 (HER2: protein found on cells). A study of 104 patients with HER2 positive cancer found that this combination of drugs had a progression-free survival (time between treatement and worsening of disease) of 4.8 months compared to treatment with an aromatase inhibitor (in this case, Arimidex) alone (2.4 months).

A second strategy combined aromatase inhibitors with gefitinib (Iressa). Gefitinib blocks the activity of epidermal growth factor receptor (EGFR: protein found on cells). One study found that administering gefitinib with anastrazole  was more effective than administering anastrozole alone.

The third strategy combined drugs that blocked the estrogen receptor, EGFR and HER2. Letrozole (Femara) is  a drug that blocks the activity of EGFR and HER2. One study of 644 stage III/IV patients who were hormone receptor positive (the estrogen and/or progesterone receptor proteins were present) found that lapatinib (Tykerb) in combination with letrozole had a progression-free survival of 11.9 months compared to 10.8 months in those treated with letrozole alone.

The fourth strategy involves blocking the activity of mTOR (receptor protein on cell). Various studies combined endocrine therapy with a drug that blocks mTOR such as everolimus (Zortress). It was found that this combination may be effective only in certain circumstances where the patient has become resistant to aromatase inhibitors.

The fifth strategy involves targeting proteins regulating cell cycle. These drugs, such as palbociclib (Ibrance) prevent cells from multiplying and are currently being evaluated for their effectiveness.

Finally, the sixth strategy involves targeting the androgen receptor. Early studies found that drugs which blocked androgen receptor (for example enzalutamide [Xtandi]) had the potential to prevent disease from worsening, and studies are ongoing to further evaluate this type of treatment.

The authors concluded that these strategies show promise in overcoming resistance to endocrine therapy. 

Talk to your doctor about strategies available to prevent resistance to endocrine therapy.