Background: Growth factor (G-CSF) support has been shown to reduce the incidence of neutropenic complications after chemotherapy; however, it can be associated with a significant increase in cost of care. Here, we reviewed G-CSF use in breast cancer patients receiving docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) regimen at a safety-net system. Methods: Parkland Health is the safety-net system that provides care to primarily uninsured/underinsured patients in Dallas County, Texas. The majority of patients treated at Parkland belong to racial and ethnic minorities. We reviewed electronic medical records of patients with HER-2 positive breast cancer who were treated with TCHP between 01/01/2017 and 12/31/2022 at Parkland. Data on patient demographics, treatment history, laboratory values, and treatment related complications were collected. Results: A total of 171 consecutive patients underwent neoadjuvant/adjuvant treatment with TCHP for HER-2 positive breast cancer. Forty-one patients (24.0%) received G-CSF for primary prophylaxis, as per discretion of treating physician. In the 130 patients (76.0%) who did not receive primary prophylaxis, G-CSF was added later in 41 patients (32.5%). Febrile neutropenia (FN), neutropenic treatment delays, and infections not meeting FN criteria accounted for the majority of cases where G-CSF was added later in the course of treatment. Overall, 529 cycles of TCHP were administered without G-CSF vs. 372 cycles with G-CSF. Without primary prophylaxis, 18.5% (24/130) of the patients developed FN vs 2.4% (1/41) for those who received primary prophylaxis, p=0.011. FN was a complication in 4.5% (24/529) of chemotherapy cycles without G-CSF vs. 1.1% (4/372) of cycles administered with G-CSF, p=0.003. In patients treated without G-CSF, the majority of FN episodes (71%) occurred within the first 3 cycles. FN resulted in a total of 150 days (median 5 days) of hospital stay resulting in $1.2 million (M) in charges (median $36,000 per admission). Universal G-CSF use in our patient population could have prevented 21 episodes of febrile neutropenia with an estimated saving of $1.05 M (hospital admission charges), at an extra cost of $1.8M (based on the pegfilgrastim Medicare average sales price (ASP) from 2017-2022). However, based on the 2023 Medicare ASP, by substituting pegfilgrastim for biosimilars, the estimated cost would have been $603,000. Conclusions: Our study did not show an FN rate >20% to warrant routine addition of G-CSF for primary prophylaxis as recommended by the NCCN. During the study period, the cost of G-CSF was prohibitive for its universal use. However, the recent introduction of G-CSF biosimilars has significantly reduced the cost burden and justifies routine G-CSF prophylaxis as a cost saving measure.