Abstract PD6-01: Mid-treatment MRI response as a surrogate for breast pCR in TNBC: Implications for neoadjuvant chemotherapy de-escalation

Abstract Background: The incorporation of pembrolizumab into neoadjuvant chemotherapy (NAC) has significantly improved treatment response and prognosis in patients with triple-negative breast cancer (TNBC). Given the aggressive nature of the KEYNOTE-522 regimen, this study aimed to explore the potential for treatment de-escalation based on radiologic response during NAC. Methods: This retrospective study included 517 patients with TNBC who underwent serial breast MRI before, during, and after NAC. Radiologic complete response (rCR) was defined as the absence of any residual mass or enhancement on breast MRI. The association between MRI-based rCR and breast pathologic complete response (pCR, defined as ypT0) was analyzed according to imaging timepoints (mid-treatment vs. post-NAC) and chemotherapy regimen: anthracycline plus cyclophosphamide followed by weekly paclitaxel (AC-T), weekly paclitaxel plus carboplatin followed by anthracycline plus cyclophosphamide (TC-AC), or TC-AC plus pembrolizumab (KN-522 regimen). Results: At the mid-treatment timepoint, the overall rCR rate was 15.5%. Notably, the KN-522 regimen demonstrated an improved mid-treatment rCR rate compared to conventional regimens: 11.6% with AC-T, 12.9% with TC-AC, and 23.6% with the KN-522 regimen. In addition, the majority of patients with rCR at the mid-treatment subsequently achieved a breast pCR: 96.2% with AC-T, 94.7% with TC-AC, and 97.1% with the KN-522 regimen. At post-NAC, the overall rCR rate increased across all treatment groups (28.0% in AC-T, 34.5% in TC-AC, and 42.4% in the KN-522 regimen). However, the corresponding breast pCR rates showed a slight decline (88.9% in AC-T, 86.3% in TC-AC, and 83.6% in KN-522). In patients with high tumor-infiltrating lymphocytes (TILs, ≥ 30%) who received KN-522 regimen and subsequently achieved rCR, the breast pCR rate increased to 94.7%, a trend not observed in the other treatment groups. At the mid-treatment timepoint, the overall rCR rate was 15.5%. The KN-522 regimen resulted in a higher mid-treatment rCR rate (23.6%) compared to AC-T (11.6%) and TC-AC (12.9%). Among patients who achieved mid-treatment rCR, subsequent breast pCR rates were high across all regimens: 96.2% (AC-T), 94.7% (TC-AC), and 97.1% (KN-522). At the post-NAC timepoint, rCR rates increased across all groups (28.0% in AC-T, 34.5% in TC-AC, and 42.4% in KN-522), although corresponding breast pCR rates slightly declined (88.9%, 86.3%, and 83.6%, respectively). Notably, among patients with high tumor-infiltrating lymphocytes (TILs ≥30%) who received the KN-522 regimen and achieved rCR, the breast pCR rate rose to 94.7%, a pattern not observed in other treatment arms. Conclusion: The rCR on mid-treatment MRI was a strong predictor of breat pCR in TNBC. The addition of pembrolizumab to NAC significantly improved the rate of excellent radiologic response at the mid-treatment timepoint. Among patients receiving the KN-522 regimen, those with high TILs revealed improved diagnostic accuracy of post-NAC MRI in predicting breast pCR. These findings suggest the potential for KN-522 regimen de-escalation based on early radiologic response, particularly in patients with high TILs. Citation Format: S. Bae, J. Kim, Y. Cha, Y. Kook, A. Kim, J. Jeong, S. Ahn. Mid-treatment MRI response as a surrogate for breast pCR in TNBC: Implications for neoadjuvant chemotherapy de-escalation 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 PD6-01.