Hormone receptors in breast cancer: An update on the uncommon subtypes

Breast cancer is the most common cancer affecting women and is the second leading cause of cancer death among US women. Estrogen receptor (ER) signaling plays a crucial role in mammary gland development and carcinogenesis. Near 80 % of invasive breast cancers are ER-positive (ER+). Endocrine therapies targeting ER have significantly improved the prognostic outcomes in the patients with ER+ breast cancer, and the therapeutic effects are strongly correlated with the levels of the ER expression in tumor cells. Despite being an ER-dependent gene product, PR is not always overexpressed in ER+ tumors, and a small subset of breast cancers demonstrates an ER+/PR- phenotype, and a rare ER-/PR+ subtype also exists. There have been controversies on the biology of these tumor types and the predictive and prognostic power of PR status. Compelling data have shown the distinct biologic characteristics of ER+/PR- and ER-/PR+ tumors. Despite that ER-low breast cancers demonstrate more similarity to ER- tumors, at least a subset of ER-low carcinomas may have a functional ER signaling. Thus, adequate PR expression is essential as its absence indicates impaired ER pathway. Assessment of PR status may not only distinguish the ER+/PR- subset from the ER+ and ER-low tumors, but also differentiate the ER-/PR+ phenotype from the ER- carcinomas, both with therapeutic implications. This article was aimed to provide an up-to-date review focusing on the clinicopathologic characteristics of uncommon subtypes of breast cancer, including ER+/PR-, ER-/PR+, and ER-low breast cancers.