A variety of approaches exist for the management of brain metastases, which often occur in patients with breast cancer. Kim Blackwell, MD, follows ASCO guidelines for the management of HER2-positive brain metastases, which suggest that systemic therapy should not change if the disease is stable from the neck down. Ruth O’Regan, MD, states that she usually refers these individuals to surgery or radiation.

Although data have demonstrated that lapatinib can penetrate the central nervous system, O’Regan says she does not feel strongly about utilizing this agent. Lee Schwartzberg, MD, mentions that he may consider using lapatinib and trastuzumab after the failure of first-line neurosurgery and/or radiation.

Clinical trials continue to assess the addition of novel treatments to standard therapies. In the BOLERO-1 trial, 719 patients with locally advanced or metastatic HER2-positive breast cancer were randomized in a 2:1 ratio to either everolimus with paclitaxel and trastuzumab, or placebo plus paclitaxel and trastuzumab. However, the addition of everolimus did not significantly improve outcomes.

In the full study population, PFS was 15 months in the everolimus arm versus 14.5 months in the placebo arm (HR = 0.89; P = .1166). Among HR-negative patients, PFS was 20 months with everolimus compared with 13 months with placebo (HR = 0.66; P = .0049). Subgroup and continued analyses will assess long-term outcomes and impacts on brain metastases rates.