Background: Patients with Hormone Receptor (HR)+ metastatic breast cancer have seen several new options that improve overall survival. Recently, there are new treatment options for patients with HER2 low expression (defined as HER2 1+ on IHC or 2+ on IHC with a negative FISH). Currently, patients who have HR+ metastatic breast cancer are treated with a combination of an aromatase inhibitor and a Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as first line. Information regarding response to therapy in this group and a correlation with HER2 expression is limited. Methods: This is a retrospective study that aimed to evaluate patients with metastatic, HR+, HER2 low or HER2 negative breast cancer between January 1, 2015 and December 31, 2022. Patients were stratified based on their HER2 status, race, presence of de-novo metastatic disease versus progression, treatment with a CDK 4/6 Inhibitor, and time to progression (defined as the date of biopsy-proved diagnosis to the date of radiographic progression). Comparative data analyses were performed using Fisher Exact and Kruskal-Wallis testing. Kaplan Meier estimates with a log rank p-value were used for survival curves, and a P-value of < 0.05 was considered statistically significant. Results: 143 patients were included in our study. Patients were divided based on their HER2 status; 33.5% had HER2 2+ disease, 55.9% had HER2 1+, and 8.4% had HER2 0. Of the patients evaluated, 66% (94/143) were Caucasian, 25% (36/143) were African American (AA), and 9% (13/143) were of other race. There was a significant difference amongst patients treated with CDK 4/6 inhibitors when stratified by race; AA patients had a higher proportion of not using a CDK4 inhibitor (43.3% vs 20.3%; p-value 0.0109). There was a significant difference between the survival curves of HER2 0, 1+, and 2+ (log rank p-value = 0.043). HER2 0 patients progressed quicker than HER2 1+ and 2+ patients. When comparing HER2 negative and low disease, a significant difference was found between the survival curves (log rank p-value = 0.0190). In patients with HER2 low (1+ and 2+ with negative FISH) and HER2 negative disease, there was no difference noted among patients who had de-novo or progression to metastatic disease, high MiB1 status (defined as >20%), whether treatment with CDK 4/6 inhibitor was used, and tumor histology. Conclusions: In our study, patients who had any HER2 expression had a longer time to progression compared to patients with no expression. Patients who had a higher expression (2+ vs 1+) displayed a longer time to progression. This may suggest that as the HER2 expression increases, they may derive a longer benefit with first line therapy. Interestingly, African American patients had a higher proportion of not using a CDK4/6 inhibitor. Larger studies are needed to evaluate these differences and determine whether any expression can be used as a prognostic marker.