Only estrogen receptor “positive” is not enough to predict the prognosis of breast cancer

Purpose: Beginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer. Methods: A retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0–2, 3–5, and 6–8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis. Results: Among the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (P < 0.0001) and significantly more likely to have high risk group (P < 0.0001) relative to higher levels of ER expression group. Conclusion: ER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.