Abstract P2-10-04: Racial differences in estrogen receptor expression, treatment, and survival among estrogen receptor positive, HER2-negative invasive breast cancers
Authors: Purrington Kristen S. , Gorski David , Simon Michael S. , Kim Seongho , Rosati Rayna , Schwartz Ann , Ratnam Manohar 
Published: March 2020

Background: African American women (AAW) are more likely to die from hormone receptor positive, HER2-negative breast cancer than European American women (EAW), even when accounting for factors including tumor stage and other clinical characteristics, although the mechanisms underlying this disparity are unclear. We recently showed that AAW with this breast cancer subtype are 75% more likely to have high predicted risk of distant recurrence than EAW using a 21-gene recurrence score, providing evidence for underlying racial differences in tumor biology. Estrogen receptor (ER) positive tumors can vary widely in the percentage of cells staining positive for ER (1-100%), and tumors with lower percent ER staining are more likely to display basal-like features typically associated with triple negative disease, a subtype that is more common among AAW. The relationship between race, ER staining levels, and clinical treatment and outcomes remains unknown. Methods: We identified 1,625 women with ER+, HER2- invasive breast cancer who received treatment at the Karmanos Cancer Institute in Detroit, MI from 2010-2017 via the Metropolitan Detroit Cancer Surveillance System (MDCSS) registry. Percentage of cells staining positive for ER (weakly ER+ = 1-10%, moderately ER+ = 11-50%, strongly ER+ = &gt;50%) was abstracted from pathology reports. Clinical outcomes and tumor characteristics were linked via the MDCSS registry. Associations between ER levels and demographic/clinical characteristics were evaluated using logistic regression models and breast cancer-specific survival was evaluated using Cox proportional hazards models. Results: Weakly, moderately, and strongly ER+ tumors accounted for 3.2%, 2.7%, and 94.1% of the sample, respectively. AAW were more than twice as likely to have weakly ER+ tumors (Odds ratio (OR)=2.39, 95% confidence interval (CI) 1.28-4.49, p=6.4 × 10−3) and moderately ER+ tumors (OR=2.79, 95% CI 1.40-5.58, p=3.7 × 10−3) than EAW. AAW with weakly ER+ tumors were 4-fold more likely to be node positive than EAW (OR=4.35, p=0.045) and AAW with moderately ER+ tumors were 3-fold more likely to be node positive than EAW (OR=3.01, p=0.28). Adjustment for tumor size at surgery did not affect the relationship between race and node status. In a multivariable logistic model predicting whether a women received endocrine therapy, women with weakly ER+ tumors were 20% less likely to receive endocrine therapy compared to those with strongly ER+ tumors (OR=0.77, p=9.4 × 10−8), and lymph node positive tumors were 15% less likely to receive endocrine therapy (OR=0.85, p=7.2 × 10−11). In contrast, receiving chemotherapy and having later stage tumors were each associated with a 10% increase in receiving endocrine therapy (chemo: OR=1.08, p=1.9 × 10−5; stage: OR=1.13. p=6.1 × 10−5). In a multivariable Cox regression analysis, race (Hazard ratio (HR)=1.70, 95% CI 1.15-2.51, p=0.0074), ER staining levels (1-10%: HR=2.72, p=0.0029; 11-50%: HR+2.41, p=0.062), node positivity (HR=3.36, p=0.0017), distant stage (HR=18.6, p=6.0 × 10−14), and endocrine therapy (HR=0.26, p=4.1 × 10−9) were significantly associated with breast cancer specific survival. While not statistically significant, the effects of both race (HR=3.94, 95% CI 0.62-25.2, p=0.15) and endocrine therapy (HR=0.11, 95% CI 0.01-1.06, p=0.056) were strongest among the weakly HR+ tumor group. Conclusions: The biology of ER+, HER2- tumors varies by race, and AAW are more likely to have weakly ER+, node-positive tumors- which are less likely to be treated with beneficial endocrine therapy- and predict poorer outcomes. A better understanding of the role of hormone signaling in these tumors would substantially affect racial differences in survival among with ER+/HER2- tumors.

Citation Format: Kristen S. Purrington, David Gorski, Michael S. Simon, Seongho Kim, Rayna Rosati, Ann Schwartz, Manohar Ratnam. Racial differences in estrogen receptor expression, treatment, and survival among estrogen receptor positive, HER2-negative invasive breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-04.