Breast cancers have traditionally been considered estrogen receptor (ER)-positive when at least 1% of tumor cells express ER. Recent ASCO/CAP guidelines, however, introduce a distinct category—ER-low-positive—for tumors with 1%–10% ER expression, reflecting the limited evidence on how low ER levels influence prognosis and treatment response. This study investigates whether ER-low tumors differ from ER-positive and ER-negative tumors in terms of outcomes and examines their predictive value for response to neoadjuvant chemotherapy (NeoCT). Following the MOOSE (Meta-analyses Of Observational Studies in Epidemiology) guidelines, we systematically searched ISI Web of Science and PubMed to identify eligible studies for meta-analysis. The investigation focused primarily on pathologic complete response (pCR), with overall survival (OS) and disease-free survival (DFS) as secondary outcomes. A total of twelve retrospective cohort studies were included. The results indicated that patients with ER-low tumors achieved higher pCR rates after neoadjuvant chemotherapy than those with ER-positive tumors, and their response was comparable to patients with ER-negative tumors. In terms of survival, ER-low breast cancers were linked to significantly poorer OS and DFS compared with ER-positive cancers, while no survival differences were observed when ER-low tumors were compared with ER-negative cases. Available evidence indicates that ER-low breast cancers resemble ER-negative tumors more closely than ER-positive ones in terms of disease-free survival (DFS) and overall survival (OS). Additionally, low ER expression appears to have predictive value for response to neoadjuvant chemotherapy (NeoCT). Given that the current evidence is rated as low to moderate in certainty, our findings highlight the urgent need for rigorously designed prospective studies to explore the molecular characteristics and optimal therapeutic approaches for ER-low breast cancers.
