Confronting Challenges and Embracing Progress in HER2+ Breast Cancer

Yara Abdou, MD, medical oncologist at the University of North Carolina (UNC) in Chapel Hill, looks back on what have been the biggest challenges in treating HER2-positive breast cancer over the past 5-10 years.

While HER2-positive breast cancer has previously shown high mortality rates, the emergence of targeted therapies including trastuzumab (Herceptin), pertuzumab (Perjeta), sacituzumab govitecan-hziy (Trodelvy), trastuzumab emtansine (T-DM1; Kadcyla), trastuzumab deruxtecan (T-DXd; Enhertu), and more, have offered promising avenues.

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0:09 | For decades, HER2-positive breast cancer was associated with poor outcomes and high mortality rates until Herceptin, or trastuzumab, was first approved in 1998 as the first anti-HER2 targeted therapy in metastatic HER2-positive breast cancer. Prior to that, patients were historically treated with traditional chemotherapy regimens and were not doing really well. In the last 5-10 years, there has been a surge in the number of HER2-targeted agents that are approved for HER2-positive disease, in addition to developments that are powerful like [antibody-drug conjugates] targeting HER2 such as trastuzumab deruxtecan that changed the treatment paradigm.

0:55 | I think 1 of the biggest challenges we face is in HER2 brain metastases because with improved systemic control, the incidence of brain metastases has really increased, and it is estimated that about 60% of patients with HER2-positive metastatic breast cancer develop brain metastases. These patients really continue to do poorly. Historically, patients with brain metastases were excluded from clinical trials. While we knew that some agents could cross the blood-brain barrier, we did not have great data in this setting.

1:31 | More recently, we are allowing our [patients with] brain metastases to enroll in clinical trials. HER2CLIMB [NCT02614794] is an excellent example. That was the first randomized trial to study [patients with] HER2-positive metastatic breast cancer with active brain metastases, which is important to accurately study the efficacy of these agents in patients with brain metastases and improve their outcomes.