Abstract P5-10-08: Estrogen receptor quantitative measures and differences in breast cancer survival
Authors: Hill D , Royce M , Lomo L , Barry M , Kang H , Wiggins C , Prossnitz E 
Published: March 2017

Introduction: In New Mexico, Hispanic women have a 1.7-fold increased risk of breast cancer-specific death compared to non-Hispanic white women. In previous studies, race/ethnic minority women have had larger survival disparities in estrogen receptor positive (ER+) than ER- disease, suggesting some aspect of ER may mediate survival outcomes. We thus conducted an extensive assessment of ER quantitative measures.

Objective: To determine whether ER percent positive and intensity differs by ethnicity, and to evaluate whether that potential difference might account for a proportion of survival disparities.

Methods: We conducted a population-based case-cohort study of first invasive breast cancer diagnosed in white females from 1997-2009 in six NM counties, identified through Surveillance Epidemiology End Results (SEER). We selected 15% of breast cancer cases and all breast cancer deaths through 2012. After IRB approval, pathology reports and tissue microarrays served as sources of ER, PR, and Her2 information. Tumors were classified according to modified intrinsic subtypes based on immunohistochemistry. Data were analyzed using Cox proportional hazards models adapted for case-cohort with weighted estimates (cohort weighted by 6.67x), and estimated hazard ratios (HR) and 95% confidence intervals (CI) using the robust variance and alpha=.05. The proportional hazards assumption was verified by Schoenfeld residuals. All analyses were adjusted for age. Interaction was assessed by inclusion of main effects and a product term (subtype* exposure).

Results: ER and intrinsic subtype information was available for 76% of the cohort (867/1143) and 70% of breast cancer deaths (689/991). Median follow up was 7.8 years. In analyses stratified by intrinsic subtype, Hispanic women experienced elevated mortality relative to non-Hispanic whites for luminal A (HR 1.9;95% CI 1.4-2.6), Luminal B (HR 2.9;95% CI 1.5-5.7), and TN tumors (HR 1.9;95% CI 1.0-3.6) but not Her2+ER- disease (HR 1.1;95% 0.3-3.4).

Overall ER Quantitative measures: Among ER+ women, breast cancer mortality decreased with increasing ER+ staining, measured by percent (p-trend=.004) or quartile (p-trend=.002). After adjustment for ER percent(ER%+), women with increased ER intensity (score&gt;2) had reduced mortality, relative to score=1 (HR 0.6;95% CI 0.4-.1.0). Results did not differ by Luminal A or B subtype (p interaction&gt; .05).

Ethnicity-specific ER quantitative measures: ER%+ distribution did not differ by Hispanic ethnicity. However, among Hispanic women, interaction terms for ER%+ (p=.04) or quartile (p=.08) by subtype in relation to breast cancer survival suggest that Hispanic women with increasing ER staining have a reduced risk of mortality in Luminal A but not Luminal B tumors. Such differences were not evident among non-Hispanic white women. In multivariate models, inclusion of ER%+ and staining intensity did not alter Hispanic survival disparity overall, but mediated 8.6% in Luminal B.

Conclusion: After inclusion of ER%+, ER staining intensity is an independent risk factor for breast cancer survival. Differences in ER quantitative measures appear to account for only a small proportion of survival disparities. Survival gaps in ER+ breast cancer may be attributable to host or other tumor factors.Introduction: In New Mexico, Hispanic women have a 1.7-fold increased risk of breast cancer-specific death compared to non-Hispanic white women. In previous studies, race/ethnic minority women have had larger survival disparities in estrogen receptor positive (ER+) than ER- disease, suggesting some aspect of ER may mediate survival outcomes. We thus conducted an extensive assessment of ER quantitative measures.

Objective: To determine whether ER percent positive and intensity differs by ethnicity, and to evaluate whether that potential difference might account for a proportion of survival disparities.

Methods: We conducted a population-based case-cohort study of first invasive breast cancer diagnosed in white females from 1997-2009 in six NM counties, identified through Surveillance Epidemiology End Results (SEER). We selected 15% of breast cancer cases and all breast cancer deaths through 2012. After IRB approval, pathology reports and tissue microarrays served as sources of ER, PR, and Her2 information. Tumors were classified according to modified intrinsic subtypes based on immunohistochemistry. Data were analyzed using Cox proportional hazards models adapted for case-cohort with weighted estimates (cohort weighted by 6.67x), and estimated hazard ratios (HR) and 95% confidence intervals (CI) using the robust variance and alpha=.05. The proportional hazards assumption was verified by Schoenfeld residuals. All analyses were adjusted for age. Interaction was assessed by inclusion of main effects and a product term (subtype* exposure).

Results: ER and intrinsic subtype information was available for 76% of the cohort (867/1143) and 70% of breast cancer deaths (689/991). Median follow up was 7.8 years. In analyses stratified by intrinsic subtype, Hispanic women experienced elevated mortality relative to non-Hispanic whites for luminal A (HR 1.9;95% CI 1.4-2.6), Luminal B (HR 2.9;95% CI 1.5-5.7), and TN tumors (HR 1.9;95% CI 1.0-3.6) but not Her2+ER- disease (HR 1.1;95% 0.3-3.4).

Overall ER Quantitative measures: Among ER+ women, breast cancer mortality decreased with increasing ER+ staining, measured by percent (p-trend=.004) or quartile (p-trend=.002). After adjustment for ER percent(ER%+), women with increased ER intensity (score&gt;2) had reduced mortality, relative to score=1 (HR 0.6;95% CI 0.4-.1.0). Results did not differ by Luminal A or B subtype (p interaction&gt; .05).

Ethnicity-specific ER quantitative measures: ER%+ distribution did not differ by Hispanic ethnicity. However, among Hispanic women, interaction terms for ER%+ (p=.04) or quartile (p=.08) by subtype in relation to breast cancer survival suggest that Hispanic women with increasing ER staining have a reduced risk of mortality in Luminal A but not Luminal B tumors. Such differences were not evident among non-Hispanic white women. In multivariate models, inclusion of ER%+ and staining intensity did not alter Hispanic survival disparity overall, but mediated 8.6% in Luminal B.

Conclusion: After inclusion of ER%+, ER staining intensity is an independent risk factor for breast cancer survival. Differences in ER quantitative measures appear to account for only a small proportion of survival disparities. Survival gaps in ER+ breast cancer may be attributable to host or other tumor factors.

Citation Format: Hill D, Royce M, Lomo L, Barry M, Kang H, Wiggins C, Prossnitz E. Estrogen receptor quantitative measures and differences in breast cancer survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-10-08.