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

Sep 22, 2026

Human epidermal growth factor receptor type 2 (HER2) overexpression occurs in 15–20% of primary invasive breast cancers, but accurate classification of HER2-low and HER2-ultralow remains challenging. This Delphi consensus study addressed testing, sampling, and reporting gaps across Asia by combining two online surveys and an expert meeting. Agreement was achieved on 33/57 closed-ended statements, with strong consensus supporting biopsy of recurrent lesions and clear guidance for pathological workflows, while further evidence is still needed for clinicopathological implications.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusion

Plain Language Summary

Keywords

Adv Ther (2026) 43:1562–1581 [https://doi.org/10.1007/s12325-025-03426-x](https://doi.org/10.1007/s12325-025-03426-x) ORIGINAL RESEARCH Addressing the Challenges in the Identification of HER2‑Low and Ultralow Breast Cancer in Asia: A Delphi Consensus Milap Shah · Rowen T. Yolo · Bethy S. Hernowo · Trung Nguyen Cong · Gong Gyungyub · Irianiwati · Lu Bach Kim · Manuelito A. Madrid · Pathmanathan Rajadurai · Pichet Sampatanukul · Shir‑Hwa Ueng · Sunil Pasricha · Benjamin Yongcheng Tan · Puay Hoon Tan · Tikamporn Jitpasutham Received: August 26, 2025 / Accepted: November 3, 2025 / Published online: February 12, 2026 © The Author(s) 2026 ABSTRACT Introduction: Human epidermal growth fac‑ tor receptor type 2 (HER2) is overexpressed in 15–20% of primary invasive breast cancers, serving as a key predictive and prognostic fac‑ tor. HER2‑low is defined as immunohistochem‑ istry (IHC) 1+ or 2+ with in situ hybridization Supplementary Information The online version contains supplementary material available at [https://doi.org/10.1007/s12325](https://doi.org/10.1007/s12325)‑025‑03426‑x. M. Shah Yashoda Hospital, Hyderabad, India e‑[mail: drmilap2000@gmail.com](mail: drmilap2000@gmail.com) [R. T](R. T). Yolo (*) Department of Anatomic Pathology, University of Santo Tomas Hospital, España Blvd, Manila, Philippines e‑mail: [rtyolo@ust.edu.ph](rtyolo@ust.edu.ph) R. T. Yolo Faculty of Pharmacy, Department of Medical Technology, University of Santo Tomas, Manila, Philippines R. T. Yolo Faculty of Medicine and Surgery, Department of Pathology, University of Santo Tomas, Manila, Philippines B. S. Hernowo Hasan Sadikin General Hospital, Bandung, Indonesia e‑[mail: bethyhernowo@gmail.com](mail: bethyhernowo@gmail.com) (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 chal‑ lenges in testing, sampling, and reporting, and to identify unmet needs in Asia. Methods: The study comprised two online sur‑ veys and a participant meeting with 15 patholo‑ gists from nine countries in Asia and the Indo‑ Pacific region. Responses were recorded for 57 T. N. Cong Department of Pathology, Hanoi Medical University, Hanoi, Vietnam e‑mail: [congtrunghmu@gmail.com](congtrunghmu@gmail.com) G. Gyungyub Department of Pathology, Asan Medical Center, Songpa‑Gu, Seoul, South Korea e‑mail: [gygong@amc.seoul.kr](gygong@amc.seoul.kr)[ ](gygong@amc.seoul.kr)Irianiwati Universitas Gadjah Mada, Yogyakarta, Indonesia e‑mail: [irianiwati@ugm.ac.id](irianiwati@ugm.ac.id) L. B. Kim Department of Pathology, Ho Chi Minh City Oncology Hospital, Ho Chi Minh City, Vietnam e‑[mail: bachkimlu1509@gmail.com](mail: bachkimlu1509@gmail.com) M. A. Madrid St. Luke’s Medical Center, Quezon City, Philippines e‑[mail: mamadrid@stlukes.com.ph](mail: mamadrid@stlukes.com.ph) 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% . Results: All participants completed both sur‑ veys and the meeting (100% response) . Consen‑ sus was reached on 33/57 closed‑ended state‑ ments (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% agree‑ ment) 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. Conclusion: This Delphi study found strong consensus on key concepts for sampling, patho‑ logical testing, interpretation, and reporting of HER2‑low and u

FAQs

How are HER2-low and HER2-ultralow defined in this study?

HER2-low is defined as immunohistochemistry (IHC) 1+ or 2+ with in situ hybridization (ISH) negative. HER2-ultralow is defined as incomplete, faint/barely perceptible membrane staining in at most 10% of tumor cells (0+/with membrane staining).

What methods were used to reach the Delphi consensus?

The study used two online surveys and a participant meeting. It involved 15 pathologists from nine Asian/Indo-Pacific countries and recorded responses using a 1–9-point Likert scale with a 75% consensus threshold.

What were the main areas where consensus was reached?

Consensus was reached on key concepts for sampling, pathological testing, interpretation, and reporting of HER2-low and ultralow breast cancer. Most participants agreed that biopsies of recurrent lesions should be performed, especially when the primary tumor was HER2-zero.

Sep 22, 2026

Upload by Alex Sinclair