Abstract P3-08-06: Lymphovascular invasion (LVI), the 21-gene recurrence score, and race in early estrogen receptor-positive, HER2-negative breast cancer: A national cancer database (NCDB) analysis
Authors: Makower Della , Lin Juan , Xue Xiaonan , Sparano Joseph A 
Published: March 2020

Abstract
Background: LVI and black race are associated with poorer prognosis in early breast cancer (BCA). The Oncotype DX 21-gene Recurrence Score (RS) is both prognostic for recurrence and predictive of chemotherapy benefit in estrogen-receptor positive (ER+), HER2-negative (HER2-) early BCA. Black women enrolled on the TAILORx trial, which assigned or randomized women with hormone receptor-positive, HER2-, node-negative (N0) BCA to adjuvant therapy based on RS, had a 1.4-fold higher risk of recurrence than white women, despite similar RS distribution, treatment, and reported adherence to endocrine therapy. No prior studies have evaluated the impact of LVI, RS, and race in the same population, to assess whether LVI contributes to racial disparities or adds prognostic information to RS.
Methods: Female patients diagnosed between 1/1/2010 (the first year LVI was collected by NCDB) and 1/1/2014 with ER+ HER2- BCA, measuring up to 5 cm, with 0-3 involved axillary nodes, treated with definitive surgery as first treatment, and with numeric RS available, were identified from the 2005-2016 NCDB database. Bivariate associations between two categorical variables were examined using the chi-square test. Multivariate Cox proportional hazards model were used to assess association between LVI, chemotherapy and RS on overall survival (OS), while adjusting age, race, tumor size, grade, LN status, median income, and education level. The estimated HR for each variable in the model, along with its 95% CI, was reported. All tests are two-sided with significance level ≤5%. All analyses were conducted using SAS 9.4.
Results: 77,425 women met inclusion criteria, 65,018 N0 and 12,407 node-positive (N+). 2870 deaths were seen. LVI was present in 12.7% of cases, and associated with poor tumor grade, high RS ≥26, and N+ (all p&lt;0.0001), but not black race. Black race was associated with with larger tumor size, poorer tumor grade, high RS ≥26, and N+ (all p&lt;0.0001). Tumor-related factors associated with poorer OS included LVI (p&lt;0.0001), larger tumor size (21-50 vs 0-20 mm, p&lt;0.0001), higher RS (11-25 vs 0-10, p=0.039, ≥26 vs 0-10, p&lt;0.0001), poor histologic grade (3 vs 1, p&lt;0.0001) and N+ (p&lt;0.0001). Demographic factors associated with worse OS were older age (p&lt;0.0001) and black race (p&lt;0.0001). Median income was inversely associated with OS (p&lt;0.0001). LVI correlated with poor grade and higher RS, and with N+ (p&lt;0.0001). LVI was associated with worse OS in the entire cohort [HR 1.241 (95% CI 1.120, 1.375, p&lt;0.0001)] and in N0 patients [HR 1.355 (95% CI 1.195, 1.536, p&lt;0.0001)], but not in N+. LVI was associated with worse OS in N0 patients with RS 11-25 [HR 1.292 (95% CI 1.074, 1.555)] and ≥26 [HR 1.553 (95% CI 1.277, 1.888)], but not in patients with RS 0-10. Test for interaction between RS and LVI was not significant.
Conclusion: LVI adds prognostic information in ER+, HER2-, N0 BCA with RS 11-100. Black race is associated with worse OS, and with adverse prognostic factors such as high grade and high RS, but not with LVI.
Citation Format: Della Makower, Juan Lin, Xiaonan Xue, Joseph A Sparano. Lymphovascular invasion (LVI), the 21-gene recurrence score, and race in early estrogen receptor-positive, HER2-negative breast cancer: A national cancer database (NCDB) analysis [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 P3-08-06.