Comprehensive Diagnostic and Therapeutic Approaches for Estrogen Receptor-Low Breast Cancer: A Multidisciplinary Perspective From Oncologists and Pathologists

Estrogen receptor (ER)-low breast cancer (BC) is a rare subtype of BC defined by ER expression between 1% and 10% and is biologically more similar to triple-negative than hormone receptor-positive BC. Conflicting data have been published regarding the benefit of endocrine therapy (ET) in this subtype, whereas the response to neoadjuvant chemotherapy and prognosis seems to be comparable with that of TNBC. ER-low BC was not included in most of the randomized clinical trials conducted among patients with TNBC, missing the opportunity to access new drugs and collect data. Recent evidence has suggested that ER-low BC might benefit from an immune-chemotherapy regimen, aligning to TNBC. International guidelines should recognize ER-low BC as a unique and heterogeneous entity that needs specific prospective clinical trials to cover the gap of knowledge for determining the best management for these patients. On the basis of the published evidence, ER-low BC should be treated as TNBC and included in clinical trials designed for TNBC. Molecular subtypes and immune biomarkers could help to tailor the treatment and identify the subgroup of patients with ER-low BC for whom ET might still play a role. In this setting, considering the recent scientific publications and current guidelines, the CamE-Lot project was developed to improve the management and diagnosis of ER-low BC by fostering collaboration between pathologists and oncologists. By using real-life data from leading centers nationwide, the project aims to describe standardized practices for diagnosing and treating this particular subtype of BC. This approach could significantly enhance consistency in clinical care, improve patient outcomes, and contribute to a deeper understanding of ER-low BC.