Abstract PS4-10-02: A Real-World Correlation Analysis on the Age at Diagnosis, Pathologic Complete Response, Germline Mutations, and Toxicity in Early Triple-Negative Breast Cancer Patients Treated with the Neoadjuvant Therapy KEYNOTE-522

Abstract Introduction: Age at diagnosis can significantly impact treatment outcomes and toxicity profiles in breast cancer. Pathologic complete response (pCR) following neoadjuvant therapy in triple-negative breast cancer (TNBC) is an established surrogate for long-term outcomes. While clinical and genetic factors have been explored as predictors of pCR, the relationship between age at diagnosis and pCR, especially in the context of immune checkpoint inhibitor-based therapy such as KEYNOTE-522 (KN522), remains unclear. The KEYNOTE-522 regimen (neoadjuvant pembrolizumab combined with a four-drug chemotherapy backbone, followed by adjuvant pembrolizumab) is a standard of care for stage II-III TNBC. We evaluated the correlations between age and pCR, germline mutation status, and treatment-related toxicities in a cohort of breast cancer patients treated with the neoadjuvant therapy, KN522 regimen. Methods: We evaluated 78 patients with early-stage TNBC enrolled in a clinical registry at this single institution. Of these, 66 (84.6%) received KN522-based neoadjuvant therapy, while others underwent chemotherapy (2.6%) or upfront surgery (12.8%). Age at diagnosis (range 23–85 years, mean 52.9 ± 14.9) was analyzed as a continuous variable, and pCR status (yes/no) was the binary outcome. We also evaluated key variables including germline testing, HER2 status, ECOG, BMI, and toxicity data. Pathologic response data was available for 72 patients (92.3%). Results: Pathologic complete response (pCR) was achieved in 51.4% (37/72) of evaluable patients. Age distribution did not differ significantly between those who achieved pCR and those who did not (median age: 52 vs. 53 years, respectively), and no significant linear correlation was observed between age and pCR (point biserial correlation r = –0.08, p > 0.3). Patients with germline BRCA1/2 mutations (13/70, 18.6%) demonstrated a numerically higher pCR rate, though statistical significance was limited by sample size. Older patients (>65 years) experienced higher rates of toxicity and treatment modifications; however, this was not associated with lower pCR rates. In the KN522 subgroup, pCR rates were slightly higher, aligning with existing trial data, but age remained a non-significant modifier of treatment response. The cohort was entirely female, 87% non-Hispanic white, and 65% Hispanic, with no significant correlation between age and race or ethnicity. Conclusion: In this real-world, retrospective cohort of early-stage TNBC patients receiving neoadjuvant therapy with KN522, pathologic complete response (pCR) was achieved in over half (51.4%) of evaluable patients with no significant association between age at diagnosis and pCR outcomes. Toxicities were common during KN522 treatment, with 100% of patients experiencing at least one toxicity. Although older patients experienced increased toxicity and treatment modifications, this did not translate into lower response rates. Older patients may experience greater rates of severe toxicity; however further prospective investigation should be considered. Germline BRCA1/2 mutation carriers showed a trend toward higher pCR, though statistical power was limited. These findings suggest age alone should not be a determining factor in predicting treatment response in early-stage breast cancer, consistent with existing KN522 trial data. These findings also emphasize the importance of incorporating age and genetic testing in personalized treatment planning. Citation Format: S. A. Haddad, D. U. Portillo, E. Kaser, A. Baig, C. F. Jones, R. Banwait, M. M. Canola. A Real-World Correlation Analysis on the Age at Diagnosis, Pathologic Complete Response, Germline Mutations, and Toxicity in Early Triple-Negative Breast Cancer Patients Treated with the Neoadjuvant Therapy KEYNOTE-522 [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 PS4-10-02.