Research advances in estrogen receptor low positive early breast cancer

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.

Keywords

• |estrogen receptor|er-low positive|breast cancer|endocrine therapy|targeted therapy|antibody-drug conjugates