Abstract Background and Rationale: The direct cost of modern systemic therapy is a growing obstacle for United States patients who rely on Medicare Part B. Two biologic rich standards dominate early breast cancer care: an immunotherapy containing regimen for triple negative disease and a dual HER2 regimen for tumors that are hormone receptor positive and HER2 positive, often called triple positive. Up to date information on the absolute Medicare and patient out of pocket cost for each regimen is limited. Objective: To measure 1 year Medicare drug spending and beneficiary coinsurance for the immunotherapy regimen used in triple negative cancer and the dual HER2 regimen used in triple positive cancer, and to test how those totals change with body size and with 340B acquisition pricing. Methods: Average Sales Price files for Medicare Part B quarter 3 2025 supplied unit prices. Doses came from National Comprehensive Cancer Network Breast Guideline version 4 2025. Rules were applied to a reference woman who weighed 70 kg and had a body surface area (BSA) 1.82 m2. For each drug the per dose rule was converted to milligrams, multiplied by cycle count, divided by the billing unit size listed in the Healthcare Common Procedure Coding System, rounded up, and multiplied by Average Sales Price plus 6 percent. Beneficiary liability was 20 percent coinsurance. Sensitivity runs repeated every calculation for 60 kg and 90 kg and for a 40 percent 340B discount. Results: For the 70 kg patient Medicare paid 212,008 USD for the immunotherapy regimen and 205,484 USD for the dual HER2 regimen. Coinsurance liabilities were 42,402 USD and 41,097 USD, respectively. Pembrolizumab accounted for more than 90 percent of triple negative cost, whereas trastuzumab plus pertuzumab accounted for more than 80 percent of triple positive cost. Changing weight from 60 kg to 90 kg moved annual immunotherapy cost by less than 0.2 percent, yet shifted dual HER2 cost from 196,539 USD to 223,302 USD (plus 13.6 percent). Coinsurance moved in parallel, from 39,308 USD to 44,660 USD. A 40 percent 340B discount lowered every total proportionally without changing the rank order. Conclusions: At 2025 quarter 3 prices Medicare pays about 200,000 USD for 1 year of either regimen and the beneficiary faces approximately 42,000 USD in coinsurance. Fixed dose pembrolizumab makes the triple negative regimen cost almost independent of body size, whereas weight based trastuzumab and pertuzumab make the triple positive regimen strongly size dependent. These updated figures quantify present financial burden and provide transparent inputs for future budget impact and cost effectiveness work. Citation Format: P. Jain, V. Majmundar, C. Bhanushali, N. Ganatra, M. Patel, R. Patel, A. Kothari, K. Patel, T. Naqvi. Medicare Part B Drug Cost Burden of Pembrolizumab Based Triple Negative and Dual HER2 Triple Positive Regimens for Early Breast Cancer at 2025 Q3 Payment Rates abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-11-01.
Jain et al. (Tue,) studied this question.