Characterizing Clinicopathologic Features of Estrogen Receptor-Positive/Progesterone Receptor-Negative Breast Cancers

Abstract

Background: While most estrogen receptor-positive (ER+) breast cancers express progesterone receptor (PR), a small subset of tumors exhibits an ER+/PR- phenotype despite the fact that PR is an ER-dependent gene product. Previous studies have shown that these tumors are generally associated with a worse clinical outcome when compared to the ER+/PR+ breast cancers, indicating that they are clinically and probably genetically different entities.

Methods: We characterized the clinicopathologic features of ER+/PR- tumors from the Surveillance, Epidemiology and End Results (SEER) database and the authors' institutional cohort.

Results: ER+/PR- tumors, constituting 12% of all breast cancers in both cohorts, less frequently occurred in Caucasians, were more likely to be of a higher histologic grade and presented with a higher stage when compared to ER+/PR+ tumors. Conversely, ER+/PR- neoplasms were more frequently seen in Caucasians, less likely to be of a higher histologic grade and less frequently presented with an advanced clinical stage when compared to ER-/PR- tumors. Further, the ER+/PR- tumors were associated with a disease-specific survival intermediate to that between ER+/PR+ and ER-/PR- tumors. An ER H-score of ≥270 was associated with a significantly superior relapse-free survival in the ER+/PR- tumors, suggesting that a near-maximal ER expression is needed to compensate for the altered ER signaling in these tumors. Pathologic stage and HER2 status were independent prognostic factors in the ER+/PR- tumors. These findings may provide additional insights in directing clinical decision making for individualized systemic therapy in the pursuit of precision medicine.

Keywords: Breast cancer; Disease-specific survival; Estrogen receptor; Progesterone receptor; Relapse-free survival.