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Background <p>HER2 overexpression drives tumor aggressiveness and poor prognosis, serving as a crucial therapeutic target in various malignancies. While HER2’s role in breast cancer metastasis and prognosis is well-documented, its heterogeneity in brain metastases (BM) across different primary tumors remains understudied. This investigation examined HER2 status in matched primary cancers and BM across multiple cancer types to evaluate HER2 alterations during metastases.</p> Methods <p>We conducted a retrospective analysis of 185 matched primary tumor-BM pairs. HER2 expression was assessed using immunohistochemistry (IHC), with equivocal cases (IHC 2+) further evaluated by silver-enhanced in situ hybridization (SISH). We analyzed associations between HER2 positivity, clinicopathological factors, and survival outcomes.</p> Results <p>Of the 185 matched cases, lung, breast, and colorectal cancers were predominant, with breast cancer showing the highest HER2 positivity rate (61.5%, <i>P</i> &lt; 0.001). HER2 positivity was detected in 14.1% (26/185) of primary tumors and 15.1% (28/185) of BM with a 7.6% (14/185) discordance rate between primary and metastatic sites. HER2 positivity in BM significantly correlated with age, primary cancer type, and BM location (<i>P</i> = 0.040, <i>P</i> &lt; 0.001, <i>P</i> = 0.045, respectively). Age, BM location, BM size, BM multiplicity, and presence of other organ metastases were identified as independent prognostic factors.</p> Conclusions <p>Our findings reveal significant HER2 heterogeneity between primary tumors and matched BM across cancer types. The observed discordance in HER2 status, particularly notable in breast cancer, underscores the necessity of HER2 status reassessment in BM for optimal targeted treatment strategies.</p>

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HER2 heterogeneity between primary cancers and brain metastases: a retrospective analysis of 185 matched pairs across multiple cancer types

  • 期刊论文

  • 发表日期：

    2026年2月20日

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  • Ji Young Lee,
  • Joo Yeon Koo,
  • Nah Ihm Kim,
  • Sung Sun Kim,
  • Hyun‑Jeong Shim,
  • Min-Hee Yi,
  • Roo Ji Lee,
  • Sue Jee Park,
  • Tae-Young Jung,
  • Kyung-Sub Moon,
  • Kyung-Hwa Lee

摘要

Background

HER2 overexpression drives tumor aggressiveness and poor prognosis, serving as a crucial therapeutic target in various malignancies. While HER2’s role in breast cancer metastasis and prognosis is well-documented, its heterogeneity in brain metastases (BM) across different primary tumors remains understudied. This investigation examined HER2 status in matched primary cancers and BM across multiple cancer types to evaluate HER2 alterations during metastases.

Methods

We conducted a retrospective analysis of 185 matched primary tumor-BM pairs. HER2 expression was assessed using immunohistochemistry (IHC), with equivocal cases (IHC 2+) further evaluated by silver-enhanced in situ hybridization (SISH). We analyzed associations between HER2 positivity, clinicopathological factors, and survival outcomes.

Results

Of the 185 matched cases, lung, breast, and colorectal cancers were predominant, with breast cancer showing the highest HER2 positivity rate (61.5%, P < 0.001). HER2 positivity was detected in 14.1% (26/185) of primary tumors and 15.1% (28/185) of BM with a 7.6% (14/185) discordance rate between primary and metastatic sites. HER2 positivity in BM significantly correlated with age, primary cancer type, and BM location (P = 0.040, P < 0.001, P = 0.045, respectively). Age, BM location, BM size, BM multiplicity, and presence of other organ metastases were identified as independent prognostic factors.

Conclusions

Our findings reveal significant HER2 heterogeneity between primary tumors and matched BM across cancer types. The observed discordance in HER2 status, particularly notable in breast cancer, underscores the necessity of HER2 status reassessment in BM for optimal targeted treatment strategies.