Expanding the treatment options for HER2-low metastatic breast cancer: Experience with trastuzumab deruxtecan in aggressive luminal HER2-low breast cancer

Abstract

The polar division of breast cancer into HER2-positive and HER2-negative subtypes has long remained clinically significance. However, up to 60% of HER2-negative tumors have HER2 receptor expression assessed by immunohistochemistry as 1+ or 2+. In the absence of gene amplification, such tumors are classified as HER2-low. Сlassical anti-HER2 agents have not improved treatment outcomes for these tumors. The development of a new generation antibody-cytostatic conjugate, trastuzumab deruxtecan, targeting the HER2 receptor, is changing diagnostic approaches and clinical practice in the treatment of metastatic HER2-low breast cancer. The results of the phase III DESTINY-Breast04 study of trastuzumab deruxtecan in patients with metastatic breast cancer with low HER2 expression became a real revolution. The median progression-free survival in the cohort of patients receiving trastuzumab deruxtecan was 9.9 months versus 5.1 months in the group of patients receiving standard chemotherapy at the physician’s choice (RR 0.50; 95% CI 0.40–0.63, P = 0.003). An objective response during therapy with trastuzumab deruxtecan was recorded in 52.3% of cases versus 16.3% in the standard treatment group. Therapy with the new drug demonstrated a favorable safety profile and did not reduce the quality of life. In this publication, we present our own experience of treating a patient with metastatic luminal HER2-low breast cancer with trastuzumab deruxtecan. Despite the aggressive course, the number of previous lines of therapy and massive liver damage, the use of trastuzumab deruxtecan made it possible to control the disease for 2 years while maintaining a high quality of life for the patient. Trastuzumab deruxtecan is a new effective treatment option for HER2-low metastatic breast cancer.