HER-2 amplification + HR-positive

The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody-drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low...These real-world data help establish the prevalence of HER2-low status and its distinct outcomes. The discrepancy in HER2-low status between the primary tumor and metastatic sites highlights the potential for changes in HER2 expression over time, exploring the interaction between HER2-low breast cancer and the tumor microenvironment and emphasizing the importance of monitoring and reassessing HER2 status at various stages to guide treatment decisions effectively and the need for more quantitative and reproducible HER assays.

P2, N=38, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P=N/A, N=80, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies.

P2, N=88, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Dec 2026

Clinical trials proposing its application in locally advanced HER2-BC have also been included. Furthermore, clinical trials showcasing the combination of Sacituzumab govitecan with numerous therapeutic modalities improving patient survival and quality of life in metastatic disease have also been included in the text.

We also analyzed DFS and OS in PCR and nonPCR patients, and there was no statistically significant difference in DFS (p=0.29) and OS (p=0.54) between HER2-0 and HER2-low cases in PCR patients, and no difference in DFS and OS between HER2-0 and HER2-low cases in nonPCR patients. In breast cancer patients receiving neoadjuvant chemotherapy, no significant differences in chemosensitivity or prognostic outcomes were observed between HER2-low and HER2-0 tumors, considering HR expression subtypes and other current clinicopathological features.

P2, N=63, Active, not recruiting, City of Hope Medical Center | Trial completion date: May 2025 --> May 2026

P1, N=40, Recruiting, Emory University | Trial completion date: Apr 2025 --> Apr 2027 | Trial primary completion date: Apr 2025 --> Apr 2026

P1, N=165, Recruiting, Iksuda Therapeutics Ltd. | Trial primary completion date: Sep 2025 --> Sep 2026

Differences exist between this group and HER2-null breast cancer. In this review, we provide an update on HER2-low and HER2-ultralow breast cancer, including background trial data, the evolution of HER2-low expression, current clinical guidelines, quality issues, and future directions.

This prompted us to develop atirmociclib (PF-07220060), a next-generation CDK4 selective inhibitor...Realized dose intensification led to greater CDK4 inhibition and deeper anti-tumor responses, pointing to CDK4 target coverage as a limiting factor of CDK4/6 inhibitor efficacy. We also highlight combinatorial agents that may counter acquired resistance to CDK4 selective inhibition and widen its clinical application.