Addressing the Challenges in the Identification of HER2-Low and Ultralow Breast Cancer in Asia: A Delphi Consensus

Human epidermal growth factor receptor type 2 (HER2) is overexpressed in 15-20% of primary invasive breast cancers, serving as a key predictive and prognostic factor. HER2-low is defined as immunohistochemistry (IHC) 1+ or 2+ with in situ hybridization (ISH) negative and HER2-ultralow is defined as membrane staining that is incomplete, faint/barely perceptible, and in at most 10% of tumor cells (0+/with membrane staining). Trastuzumab deruxtecan has shown improved outcomes in multiple clinical trials between these groups. A Delphi study was conducted to address challenges in testing, sampling, and reporting, and to identify unmet needs in Asia.

The study comprised two online surveys and a participant meeting with 15 pathologists from nine countries in Asia and the Indo-Pacific region. Responses were recorded for 57 close-ended and 33 open-ended statements using a 1-9-point Likert scale ranging from agreement to disagreement with a consensus threshold of 75%.

All participants completed both surveys and the meeting (100% response). Consensus was reached on 33/57 closed-ended statements (survey 1, 27/47; survey 2, 6/21), while 24/57 did not reach consensus. Ninety-three percent of participants agreed that biopsies of recurrent lesions should be performed, especially if the primary tumor was HER2-zero. Initially, participants did not reach consensus (73% agreement) on reassessing HER2 results for metastatic lesions scored as HER2-zero but later reached consensus (80% agreement). All testing-related questions reached consensus in survey 1.

This Delphi study found strong consensus on key concepts for sampling, pathological testing, interpretation, and reporting of HER2-low and ultralow breast cancer. While the opinions expressed align with current guidelines, more evidence on the clinicopathological implications is needed.