De-escalation and Sequencing Strategies Shape HER2-Positive Breast Cancer Care at SABCS 2025
Key Points
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The NeoCARHP trial suggested that carboplatin may be omitted in select patients with low-risk, early HER2-positive breast cancer without compromising pathologic complete response (pCR).
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Maintenance strategies in metastatic disease are increasingly tailored by hormone receptor status.
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Tucatinib-based regimens remain a strong choice for patients with central nervous system (CNS) metastases.
Clinical trials presented at the 2025 San Antonio Breast Cancer Symposium highlighted a growing emphasis on personalization and de-escalation in early and metastatic HER2-positive breast cancer treatment. In a discussion between Ya Haddy Sallah, MD, MPH, of Memorial Sloan Kettering Cancer Center, and Nerea Lopetegui Lia, MD, of The Ohio State University, new data emphasized how treatment intensity can be better matched to patient risk.
In early-stage HER2-positive disease, Dr. Lopetegui Lia cited results from the NeoCARHP trial, a randomized phase 3 non-inferiority study evaluating whether carboplatin can be omitted from standard neoadjuvant TCHP. The trial compared TCHP with THP and demonstrated similar pCR rates between the two regimens. These findings raise the possibility that select patients may safely avoid carboplatin-associated toxicity.
Dr. Lopetegui Lia emphasized that de-escalation should be considered, particularly for patients with node-negative disease or low disease burden. While the data are encouraging, she said that a longer follow-up is needed.
In metastatic disease, the experts explored data from the HER2CLIMB-05 and PATINA studies that are informing maintenance strategies. Dr. Lopetegui Lia suggested that trastuzumab, pertuzumab, and tucatinib may be preferred in hormone receptor (HR)-negative disease, while the PATINA approach—adding palbociclib and endocrine therapy to trastuzumab and pertuzumab—may be better suited for HR-positive patients. For patients with brain metastases, tucatinib-based therapy remains a favored option given its CNS activity.