Background: In the US, African American (AA) women have similar incidence of breast cancer (BC) as White women, but have 40% higher BC mortality. This disparity results from differences in biological and social determinants of cancer treatment. Previous studies have focused primarily on first-line(1L) treatment, but little is known about racial differences in treatment beyond 1L and the impact these differences may have on outcomes. Methods: This analysis utilized data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database and included pts with mBC initiating 2L treatment between 2/3/2015-2/29/2020. 2L treatment was caterogized broadly as CDK 4/6 inhibitors (CDKi), endocrine monotherapy, everolimus combination therapy, and chemotherapy and other systemic therapies. Real-world overall survival (rwOS) was defined as time from 2L initiation to death (censored at last EHR activity). Multinomial logistic regression was used to assess the likelihood of 2L treatment between AA and White (reference) pts, adjusted for demographics and clinical factors, including ECOG performance score, 1L treatment and 1L progression. Median rwOS was estimated using the Kaplan-Meier method and adjusted hazard ratios (aHR) were estimated using multivariable Cox proportional hazards models additionally adjusted for 2L treatment. Stratified analysis was conducted by 1L and 2L treatment. Results: A total of 389 AA and 2776 White pts were included. Compared to White pts, AA pts were younger (median age: 61 vs 65) and more likely to be under-insured (8% vs 3%), and present with de novo metastatic disease (30% vs 26%). AA pts were also less likely to receive CDKi in 2L (29% vs 35% in White), but this difference was not statistically significant after adjustment (OR = 0.83; 95% CI: 0.62-1.11). Compared to White pts who had a median rwOS of 25.6 months (95% CI: 24.5-27.4), AA pts had a median rwOS of 20.4 months (95% CI: 17.3-24.0). Poorer rwOS among AA pts was observed across all 2L treatment groups. After adjusting for covariates and 2L treatment, the observed rwOS difference was no longer statistically significant. However, in stratified analysis among pts who did not receive 1L CDKi, AA pts had 48% higher hazard of death if they received 2L CDKi (aHR = 1.48; 95% CI: 1.08-2.00), and 49% higher hazard of death if received 2L endocrine monotherapy (aHR = 1.49; 95% CI: 1.15-1.94). In contrast, adjusted rwOS was similar between AA and White pts among those who received 1L CDKi. Conclusions: These exploratory findings suggest that AA pts were less likely, partially associated with other factors, to receive CDKi at 2L. In addition, AA pts had worse rwOS than White pts even after receiving 2L CDKi among those who did not receive 1L CDKi. This disparity was not observed among patients who received 1L CDKi.