Research advances in estrogen receptor low positive early breast cancer

Yizi JIN; Mingxi LIN; Cheng ZENG; Qing GUO; Jian ZHANG

doi:10.19401/j.cnki.1007-3639.2024.10.007

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Research advances in estrogen receptor low positive early breast cancer

Review | 更新时间：2025-12-31

- Research advances in estrogen receptor low positive early breast cancer
- China Oncology Vol. 34, Issue 10, Pages: 972-978(2024)
- 作者机构：
  
  复旦大学附属肿瘤医院肿瘤内科，复旦大学附属肿瘤医院Ⅰ期临床试验病房，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  ZHANG Jian
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.10.007
  CLC： R737.9
- Received：20 September 2022，
  
  Revised：2024-10-01，
  
  Published：30 October 2024
- 稿件说明：
移动端阅览
Yizi JIN, Mingxi LIN, Cheng ZENG, et al. Research advances in estrogen receptor low positive early breast cancer[J]. China Oncology, 2024, 34(10): 972-978.
DOI：

Yizi JIN, Mingxi LIN, Cheng ZENG, et al. Research advances in estrogen receptor low positive early breast cancer[J]. China Oncology, 2024, 34(10): 972-978. DOI： 10.19401/j.cnki.1007-3639.2024.10.007.

摘要

内分泌治疗是雌激素受体（estrogen receptor，ER）阳性早期乳腺癌重要的辅助治疗手段。ER低表达（免疫组织化学染色1% ~ 10%）人群近年来受到广泛关注，该群体占乳腺癌总体人群的3% ~ 9%，辅助内分泌治疗效果相对有限。虽然ER低表达患者在乳腺癌人群中占比较低，但由于乳腺癌患者整体人群数量庞大，该群体的临床需求不容忽视。多项研究提示，ER低表达乳腺癌在肿瘤的分子生物学特征、临床病理学特征及患者预后等方面与ER阳性乳腺癌差异较大，更类似于ER阴性乳腺癌。对于ER低表达早期乳腺癌的内分泌治疗获益及疗程界定仍存在争议，缺乏大型前瞻性临床研究的证据。多项回顾性研究及meta分析结果显示，该人群接受辅助内分泌治疗可能获益有限，应慎重考虑；联合细胞周期蛋白依赖性激酶（cyclin-dependent kinase，CDK）4/6抑制剂行辅助治疗的获益仍有待未来数据佐证。部分ER低表达乳腺癌患者可综合考虑其他危险因素进行辅助化疗。除传统化疗外，抗体药物偶联物（如戈沙妥珠单抗、Dato-DXd）、多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase，PARP]抑制剂、免疫治疗ER低表达早期乳腺癌的临床研究也正在进行中。其中包括：评估戈沙妥珠单抗联合帕博利珠单抗辅助治疗术后高危的人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）阴性、ER和孕激素受体（progesterone receptor，PR）<10%患者的Ⅲ期ASCENT-05研究，评估戈沙妥珠单抗辅助治疗术后高危HER2阴性患者的Ⅲ期SASCIA研究，以及评估Dato-DXd联合度伐利尤单抗新辅助治疗的Ⅲ期TROPION-Breast04研究；此外，一项针对奥拉帕利联合度伐利尤单抗新辅助治疗三阴性乳腺癌（triple-negative breast cancer，TNBC）及ER低表达乳腺癌的研究（NCT03594396）正在探索中，结果值得期待。本文介绍ER低表达乳腺癌的定义、临床病理学特征及患者预后，并阐述HER2阴性、ER低表达早期乳腺癌的治疗现状以及未来潜在的治疗策略。

Abstract

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor (ER)-positive breast cancer. ER-low-positive (immunohistochemistry staining 1%-10%) breast cancer has drawn widespread attention in recent years. This group accounts for 3%-9% of overall breast cancer patients. The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer. Although the proportion of patients with low ER expression in breast cancer population is relatively low

the clinical needs of this population can not be ignored because of the large number of breast cancer patients. A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer

and is similar to ER-negative breast cancer in terms of molecular and biological characteristics

clinical features and prognosis. There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer

and there is a lack of evidence from large-scale prospective studies. Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy

and therefore endocrine therapy should be considered with caution in this population. The benefit of adjuvant therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors is yet to be supported by future data. Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors. Additionally

clinical trials that test antibody-drug conjugates (such as sacituzumab govitecan and Dato-DXd)

poly (ADP-ribose) polymerase (PARP) inhibitors

and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing

including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in high-risk human epidermal growth factor receptor 2 (HER2)-negative

ER and progesterone receptor (PR)<10% patients after surgery

the phase Ⅲ SASCIA study evaluating the adjuvant therapy of sacituzumab govitecan in high-risk HER2-negative patients after surgery

and the phase Ⅲ TROPION-Breast 04 study evaluating the neoadjuvant therapy of Dato-DXd combined with durvalumab. In addition

a neoadjuvant treatment for triple-negative breast cancer (TNBC) and ER-low expression breast cancer with olaparib and durvalumab (NCT03594396) is being explored

and the results are worth expecting. This article aimed to introduce the definition

clinical and pathological characteristics

and prognosis of ER-low breast cancer

and expound on the current treatment status and potential therapeutic strategies for HER2-negative

ER-low-positive early breast cancer in the future.

关键词

Keywords

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