Assessment of heterogeneous response of primary tumor and nodal disease to neoadjuvant therapy in invasive breast cancer
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Abstract
Objective: To assess heterogeneous pathological responses of the primary tumor and axillary lymph nodes following neoadjuvant therapy (NAT) in invasive breast carcinoma and to identify clinicopathological factors associated with variable response patterns, including pathological complete response (pCR).
Methods: This cross-sectional study included node-positive, non-metastatic patients with invasive breast cancer who received NAT followed by definitive surgery between October 2024 and June 2025. Tumor and nodal responses were assessed on final histopathology and categorized as pCR, heterogeneous response, or non-complete response. Clinicopathological and biological variables were recorded. Associations were evaluated using univariate analysis, while multinomial logistic regression identified independent predictors of tumor and nodal response.
Results: Among 169 patients, heterogeneous response occurred in 53 (31.4%), non-complete response in 95 (56.2%), and pCR in 21 (12.4%). Within the heterogeneous group, 24 (45.3%) patients achieved breast pCR with residual nodal disease, while 29 (54.7%) showed nodal pCR with residual breast tumor. A significant association was observed between breast and nodal responses (p <0.001). Tumor grade III (50.9%, p =0.017), triple-negative receptor status (41.5%, p <0.001), and type of NAT (p =0.032) were significantly associated with heterogeneous response. Residual tumor size (p =0.010), lymphovascular invasion (p =0.023), ductal carcinoma in situ (p =0.007), and extranodal extension (p <0.001) independently predicted tumor and nodal response, but not heterogeneous response specifically.
Conclusion: Discordant pathological responses between primary breast tumors and axillary lymph nodes after NAT are frequent and reflect biological heterogeneity. Recognizing these patterns is crucial for individualized surgical planning and optimization of post-neoadjuvant treatment strategies.
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