Tailoring Therapy to Be Just Right in HER2-Positive Early-Stage Breast Cancer: The Goldilocks Problem
Source : https://ascopubs.org/doi/10.1200/OP.21.00125
Treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer was transformed when pharmacologic targeting of the HER2 oncoprotein became possible, marked by the approval of trastuzumab in 1998. Since then, a broad range of HER2-targeted agents have been introduced to the therapeutic armamentarium, including monoclonal antibodies, antibody-drug conjugates, and oral tyrosine kinase inhibitors, with several others in clinical development.
Key Points
• In the current commentary from JCO Oncology Practice, authors reviewed recent advances in the treatment of HER2-positive including the utilization of escalation strategies in high-risk patients and de-escalation strategies in low-risk patients. They noted that in both the pre- and post-treatment settings, risk stratification in HER2-positive early-stage breast cancer has depended on clinical and pathologic staging.
• When following current guidelines, the authors wrote that clinicians likely overtreat or undertreat patients. They explained that 10%-40% of patients with early-stage HER2-positive breast cancer demonstrate a pCR following neoadjuvant treatment with chemotherapy-free regimens, thus suggesting pronounced sensitivity to HER2-targeted therapies. Whereas “disease relapse (including in the CNS) remains an issue in many patients despite receiving the most aggressive existing neoadjuvant and adjuvant regimens.”
• The authors cited various ongoing clinical trials addressing heterogeneity in treatment response that involve treatments that have demonstrated efficacy in the metastasis, such as the CompassHER2-RD trial, which is analyzing the addition of the CNS-penetrating oral tyrosine kinase inhibitor tucatinib to adjuvant T-DM1 in those with residual disease following neoadjuvant treatment.
• According to the authors, “The question remains: Can we add to traditional clinical risk stratification and use advanced molecular or radiologic techniques to better tailor therapy for HER2-positive breast cancer?”