Comparing the effects of combined PI3K inhibitor/endocrine therapy versus endocrine therapy alone in ER-positive breast cancer

This study investigated whether the addition of the PI3K inhibitor pictilisib (Stemolecule GDC-0941) can increase the anti-tumor effects of anastrozole (Arimidex) in patients with estrogen receptor-positive (ER-positive) primary breast cancer (BC). Combined treatment with pictilisib (PIC) and anastrazole (ANA) was associated with increased anti-tumor action.

The PI3K signaling pathway influences the lifespan and growth of the cell. Malfunctions in this pathway are believed to have a role in ER-positive BC (dependent on the hormones estrogen or progesterone for growth). Treatments that targets this pathway alongside standard hormone treatment may be beneficial for certain patient subgroups.

This study involved 70 postmenopausal women with newly diagnosed ER-positive, HER2-negative BC. The study also noted the luminal subtype of the cancer (luminal A and B are two of the four common subtypes of BC). Patients were assigned to either combined therapy with PIC and ANA or treatment with ANA alone for a period of 2 weeks prior to surgery.

Patients who received combination treatment experienced an 83.8% decrease in Ki-67 (a protein present in growing cancer cells, often used to determine the aggression of the disease) while those on ANA alone experienced a 66% decrease. Patients with the luminal B subtype experienced an 86.5% decrease with combination treatment, compared to a 63.6% decrease with ANA alone. Patients with the luminal A subtype did not benefit from the addition of PIC to their treatment.

The study concluded that the addition of pictilisib to anastrazole treatment was associated with a reduction in tumor cell growth, particularly in patients with the luminal B subtype of BC.

Patients in this study were treated for a short period of time and did not all receive the same dose, meaning that the long term benefits of treatment and ideal dosage must be confirmed. 

Discuss the pros and cons of adding a PI3K inhibitor to your treatment with your doctor.