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Purpose <p>HER2-low breast cancer has emerged as a therapeutic category following the DESTINY-Breast04 trial, where trastuzumab deruxtecan (T-DXd) improved survival. As the Ventana 4B5 assay was the companion diagnostic in this trial, many patients previously tested with the Dako HercepTest required reassessment. However, the frequency and clinical predictors of discrepancies between these assays remain unclear. This study aimed to evaluate discordance frequency between HercepTest<sup>®</sup> and 4B5 and identify associated clinicopathological factors.</p> Methods <p>We retrospectively analyzed patients who underwent prior HER2 testing with HercepTest and subsequent reassessment with 4B5 between May 2023 and November 2024 at our institution. The primary endpoint was reassessment discordance, and secondary analyses examined the clinicopathological predictors of discordance.</p> Results <p>Eighty-four patients (median age: 58 years) were included. Specimens were obtained from primary tumors (28.6%) and metastatic lesions (71.4%); 15.5% were resections and 84.5% were biopsies. The discordance rate between HercepTest<sup>®</sup> and 4B5 was 60.7%, most commonly a shift from 2 + to 1+, followed by 1 + to 0. Multivariable analysis identified progesterone receptor negativity (odds ratio [OR] 3.84, 95% confidence interval [CI] 1.39–11.59, <i>p</i> = 0.01) and metastatic site sampling (OR 3.77, 95% CI 1.14–13.67, <i>p</i> = 0.03) as independent predictors. Approximately one-quarter of discordant patients lost their HER2-low status and potential eligibility for T-DXd.</p> Conclusions <p>Discordance between HercepTest<sup>®</sup> and 4B5 is frequent and clinically consequential, leading to reclassification based on 4B5 that affects eligibility assessment in a substantial subset of patients. These findings highlight the need for careful interpretation of HER2 results in real-world reassessment and increased awareness of diagnostic variability in HER2-low classification.</p>

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Clinical implications of discordance in HER2 reassessment from HercepTest to 4B5 in metastatic breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Yuhei Yamaguchi,
  • Mai Hoshino,
  • Tatsunori Shimoi,
  • Hiroki Tamura,
  • Yutaka Natori,
  • Takuro Saiki,
  • Taro Yamanaka,
  • Rui Kitadai,
  • Ayumi Saito,
  • Shosuke Kita,
  • Aiko Maejima,
  • Yuki Kojima,
  • Kazuki Sudo,
  • Akiko Miyagi Maeshima,
  • Takeshi Murata,
  • Shin Takayama,
  • Yasuto Naoi,
  • Kan Yonemori,
  • Masayuki Yoshida

摘要

Purpose

HER2-low breast cancer has emerged as a therapeutic category following the DESTINY-Breast04 trial, where trastuzumab deruxtecan (T-DXd) improved survival. As the Ventana 4B5 assay was the companion diagnostic in this trial, many patients previously tested with the Dako HercepTest required reassessment. However, the frequency and clinical predictors of discrepancies between these assays remain unclear. This study aimed to evaluate discordance frequency between HercepTest® and 4B5 and identify associated clinicopathological factors.

Methods

We retrospectively analyzed patients who underwent prior HER2 testing with HercepTest and subsequent reassessment with 4B5 between May 2023 and November 2024 at our institution. The primary endpoint was reassessment discordance, and secondary analyses examined the clinicopathological predictors of discordance.

Results

Eighty-four patients (median age: 58 years) were included. Specimens were obtained from primary tumors (28.6%) and metastatic lesions (71.4%); 15.5% were resections and 84.5% were biopsies. The discordance rate between HercepTest® and 4B5 was 60.7%, most commonly a shift from 2 + to 1+, followed by 1 + to 0. Multivariable analysis identified progesterone receptor negativity (odds ratio [OR] 3.84, 95% confidence interval [CI] 1.39–11.59, p = 0.01) and metastatic site sampling (OR 3.77, 95% CI 1.14–13.67, p = 0.03) as independent predictors. Approximately one-quarter of discordant patients lost their HER2-low status and potential eligibility for T-DXd.

Conclusions

Discordance between HercepTest® and 4B5 is frequent and clinically consequential, leading to reclassification based on 4B5 that affects eligibility assessment in a substantial subset of patients. These findings highlight the need for careful interpretation of HER2 results in real-world reassessment and increased awareness of diagnostic variability in HER2-low classification.