Recent developments in HER2-targeted therapy present new challenges for physicians treating patients with metastatic HER2-positive (HER2+) breast cancer, including how to treat patients with brain metastases, how to properly sequence therapies and make sequencing decisions, and how to identify and manage interstitial lung disease (ILD). Experts discussed these topics in a virtual CancerNetwork[R] Around the Practice presentation, "HER2+ Breast Cancer: Special Challenges and Expert Insight," held April 20, 2021, and moderated by Adam M. Brufsky, MD, PhD. Members of the audience also participated in an interactive online platform by submitting responses to polling questions that were subsequently discussed by the panelists.
Screening Asymptomatic Patients for Brain Metastases
When polled about how often they screen asymptomatic patients with metastatic HER2+ breast cancer for brain metastases, 60% of audience respondents answered "sometimes" (Figure 1). In the follow-up question, "How often do you treat prophylactically for brain metastases in asymptomatic patients with HER2+ breast cancer?" 50% of respondents answered "never," 25% answered "rarely," and 25% answered "sometimes" (Figure 2).
The panelists then discussed approaches to management of a 37-year-old woman with a 5-cm lump in her right breast (Table). Immunohistochemistry (IHC) showed HER2+ breast cancer. The patient obtained a pathologic complete response to 6 cycles of neoadjuvant chemotherapy (docetaxel, carboplatin, trastuzumab, and pertuzumab), lumpectomy, and radiation, followed by maintenance therapy with trastuzumab and pertuzumab. After 32 months, the patient returned to the clinic with fatigue and persistent cough; a CT showed 3 nodules in the left upper lobe of the lung. IHC of the lung biopsy revealed HER2+ metastases, and the patient was treated with docetaxel, trastuzumab, and pertuzumab (THP) chemotherapy and given bisphosphonates every 3 months. After 24 months, a routine CT showed 4 new liver metastases.
The panelists and the poll respondents were evenly divided about whether to screen this patient for brain metastases (Figure 3). The National Comprehensive Cancer Network (NCCN) guidelines recommend brain MRI with contrast for patients with recurrent or stage IV disease who have symptoms suggestive of central nervous system (CNS) metastases, and Neil M. Iyengar, MD, said that he does not routinely screen asymptomatic patients because of the lack of evidence to support a corresponding survival beneifit. (1)
The NCCN guidelines state that clinical trials offer the best management for patients with cancer and encourage participation when possible. (1) Sara A. Hurvitz, MD, recommended referring the patient for enrollment in the HER2CLIMB-02 trial (NCT03975647), a randomized, double-blind, placebo-controlled, phase 3 study to evaluate the efficacy and safety of tucatinib plus trastuzumab emtansine (T-DM1) in patients with unresectable locally advanced or metastatic HER2+ breast cancer. (2) The study uses baseline brain MRI for all participants. (2)
V. K. Gadi, MD, PhD, said that he is increasingly inclined to screen asymptomatic patients because of the increased availability of trials for patients with CNS metastases. Hurvitz added that patient preference also influences her screening decisions.
Prophylactic Treatment of CNS Metastases
Metastases within the CNS are common among patients with HER2+ breast cancer, occurring in 25% to 50% of patients...