Phase 2 trial of trastuzumab and/or everolimus in hormone-resistant HER2-negative metastatic breast cancer

576^ Background: Increased signaling through growth factor receptor pathways, including HER2, has been demonstrated to play a role in resistance to endocrine therapy. Efficacy of inhibiting HER2 and mTOR in HER2-negative, hormone-resistant breast cancer has been previously demonstrated. We evaluated the ability of inhibition of HER2 with trastuzumab (TRAST) and/or mTOR with everolimus (EVER) to reverse resistance to endocrine therapy in patients with hormone receptor (HR)-positive HER2-negative metastatic breast cancer (MBC). Methods: Eligibility included HR-positive, HER2-negative (IHC 1+ or 2+ and/or FISH negative) MBC on metastatic biopsy and documented progression within 6-months of starting an endocrine agent in the metastatic setting. Patients continued on the endocrine agent they had experienced disease progression on and were randomized to receive TRAST (8mg followed by 6mg every 3-weeks) or EVER 10mg daily. At disease progression the other agent (TRAST or EVER) was added. Biopsies of metastatic l...