Scholarlink

Purpose <p>HER2 expression is crucial in breast cancer classification and treatment. Traditionally, tumors were categorized as HER2-positive or HER2-negative, but HER2-low (IHC 1 + or 2 + without ISH amplification) has emerged as a new classification. Among HER2-negative cases, HER2-ultralow (≤ 10% faint HER2 staining) and HER2-null (completely HER2-negative) have been proposed. While differences between HER2-low and HER2-zero tumors are studied, <i>little is known about the clinical and prognostic characteristics of HER2-ultralow breast cancer</i>. This study <i>aimed to clarify</i> the clinical characteristics, immune microenvironment, treatment response, and prognosis of HER2-ultralow tumors, <i>with HER2-null and HER2-low tumors analyzed as comparators</i>.</p> Methods <p>A retrospective analysis of 244 HER2-negative breast cancer patients treated with neoadjuvant chemotherapy (NAC) at Osaka Metropolitan University Hospital (2007–2018) classified tumors into HER2-low (41.0%), HER2-ultralow (36.1%), and HER2-null (23.0%). <i>Clinicopathological features</i>,<i> tumor-infiltrating lymphocyte (TIL) counts</i>,<i> pathological complete response (pCR)</i>,<i> and prognostic outcomes (disease-free survival [DFS] and overall survival [OS]) were evaluated</i>.</p> Results <p>HER2-ultralow tumors showed significantly higher estrogen receptor (ER) positivity compared with HER2-null tumors (51.8% vs. 19.6%, p &lt; 0.001), and also tended to have higher progesterone receptor positivity (p = 0.048). In contrast, HER2-null tumors were associated with younger age (median 50.0 vs. 56.0 years, p = 0.004) and higher TIL density (50.0% vs. 36.8%, p = 0.016). The overall pCR rate was 27.9%. DFS showed no significant differences among the three groups (p = 0.087), but OS was significantly worse in HER2-null compared with Not HER2-null tumors (p = 0.026, HR = 0.454). HER2-ultralow cases demonstrated an intermediate prognosis between HER2-low and HER2-null (OS comparison with HER2-null,&gt;p= 0.101).</p> Conclusion <p>HER2-ultralow tumors <i>represent a distinct subgroup characterized by higher hormone receptor positivity</i>, whereas HER2-null tumors were associated with younger age, higher TIL density, and poorer survival. <i>These findings emphasize the clinical significance of refining HER2-negative subclassification to distinguish HER2-ultralow</i>,<i> while acknowledging limitations of sample size and retrospective design</i>.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Clinical characteristics and prognostic impact of HER2-ultralow breast cancer and tumor-infiltrating lymphocytes (TILs)

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月28日

查看全文
  • Koji Takada,
  • Shinichiro Kashiwagi,
  • Mariko Nishikawa,
  • Asuka Kochi,
  • Chika Watanabe,
  • Haruhito Kinoshita,
  • Kana Ogisawa,
  • Masatsune Shibutani,
  • Tamami Morisaki

摘要

Purpose

HER2 expression is crucial in breast cancer classification and treatment. Traditionally, tumors were categorized as HER2-positive or HER2-negative, but HER2-low (IHC 1 + or 2 + without ISH amplification) has emerged as a new classification. Among HER2-negative cases, HER2-ultralow (≤ 10% faint HER2 staining) and HER2-null (completely HER2-negative) have been proposed. While differences between HER2-low and HER2-zero tumors are studied, little is known about the clinical and prognostic characteristics of HER2-ultralow breast cancer. This study aimed to clarify the clinical characteristics, immune microenvironment, treatment response, and prognosis of HER2-ultralow tumors, with HER2-null and HER2-low tumors analyzed as comparators.

Methods

A retrospective analysis of 244 HER2-negative breast cancer patients treated with neoadjuvant chemotherapy (NAC) at Osaka Metropolitan University Hospital (2007–2018) classified tumors into HER2-low (41.0%), HER2-ultralow (36.1%), and HER2-null (23.0%). Clinicopathological features, tumor-infiltrating lymphocyte (TIL) counts, pathological complete response (pCR), and prognostic outcomes (disease-free survival [DFS] and overall survival [OS]) were evaluated.

Results

HER2-ultralow tumors showed significantly higher estrogen receptor (ER) positivity compared with HER2-null tumors (51.8% vs. 19.6%, p < 0.001), and also tended to have higher progesterone receptor positivity (p = 0.048). In contrast, HER2-null tumors were associated with younger age (median 50.0 vs. 56.0 years, p = 0.004) and higher TIL density (50.0% vs. 36.8%, p = 0.016). The overall pCR rate was 27.9%. DFS showed no significant differences among the three groups (p = 0.087), but OS was significantly worse in HER2-null compared with Not HER2-null tumors (p = 0.026, HR = 0.454). HER2-ultralow cases demonstrated an intermediate prognosis between HER2-low and HER2-null (OS comparison with HER2-null,>p= 0.101).

Conclusion

HER2-ultralow tumors represent a distinct subgroup characterized by higher hormone receptor positivity, whereas HER2-null tumors were associated with younger age, higher TIL density, and poorer survival. These findings emphasize the clinical significance of refining HER2-negative subclassification to distinguish HER2-ultralow, while acknowledging limitations of sample size and retrospective design.