Abstract P1-07-09: Estrogen receptor positivity: 10% or 1%?
Authors: Yi M , Huo L , Koenig KB , Mittendorf EA , Meric-Bernstam F , Kuerer HM , Bedrosian I , Symmans WF , Hortobagyi GN , Crow JR , Shah RR , Hunt KK 
Published: August 2014

Background. Guidelines by the American Society of Clinical Oncology and the College of American Pathologists recently recommended that estrogen receptor (ER) status should be considered positive if 1% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. Historically, 10% nuclear staining defined ER-positive status and impacted decision-making regarding endocrine therapy. Currently, no optimal threshold exists for ER either by clinically validating patient outcomes in prospective clinical trials or independently validated from systematically collected archived specimens from randomized clinical trials. In this study, we examined patient, tumor and treatment differences among patients by ER status: ER-positive ≥10%, ER-positive 1–10% and ER negative (&lt;1%). We compared recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) among patients with different ER staining categories and adjusted by clinical stage, adjuvant chemo and endocrine therapy.

Method. Patients with primary breast carcinoma treated at our center who had complete ER status from January 1990 to December 2011 were included in this study. Patients were excluded if they presented with recurrent or metastatic disease. For statistical analyses, patients who underwent surgery for breast cancer were separated into three groups: ER-positive ≥10%, ER-positive 1–10% and ER negative. Analyses comparing various clinical and pathologic characteristics among patients with different ER status were performed. Survival rates were calculated by the Kaplan-Meier method.

Result. Patients whose tumors were ER-positive 1–10% (2.7%) were younger (median age 53 Vs. 56 years, P &lt; 0.0001), more likely to have invasive ductal carcinoma histology with more advanced disease (clinical stage II/III 50.4% Vs. 37.3%, p &lt; 0.0001), and were more likely to receive neoadjuvant chemotherapy (40.9% vs. 25.6%, P &lt; 0.0001), adjuvant chemotherapy (45.5% vs. 31.2%, P &lt; 0.0001), and less likely to receive adjuvant endocrine therapy (19.5% vs. 78.6%, P &lt; 0.0001) compared to patients with ER-positive tumors ≥ 10%. They were also more likely to have HER-2-positive (29.1% vs. 13.4%, P &lt; 0.0001) and grade III disease (82.1% vs. 29.6%, P &lt; 0.0001). Compared to patients with ER negative, patients with ER-positive 1–10% had earlier stage disease (clinical stage II/III 50.4% Vs. 59.3%, p = 0.01), were less likely to receive neoadjuvant chemotherapy (40.9% vs. 48.2%, p = 0.02), and more likely to receive adjuvant endocrine therapy (19.5% vs. 12.6%, p = 0.002). At a median follow-up of 5.1 years, patients with ER-positive 1–10% had worse RFS, DFS and OS rates compared to patients with ER-positive tumors ≥ 10%. The RFS, DFS and OS rates between patients with ER-positive 1–10% and ER negative did not differ significantly. Patients with ER-positive 1–10% and negative still had worse RFS, DSS and OS rates compared to patients with ER-positive tumors ≥ 10% after adjusted by clinical stage, adjuvant chemo and endocrine therapy.

Conclusion. Patients whose tumors are ER-positive at 1–10% have clinical and pathologic characteristics different from those whose tumors are ER-positive ≥10%. Similar to patients whose tumors are ER negative, those with ER-positive disease at 1–10% do not appear to benefit from endocrine therapy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-09.