Immunohistochemical Subtype Conversion and Pathological Response After Neoadjuvant Chemotherapy in Luminal B HER2-Negative Locally Advanced Breast Cancer: A Cross-Sectional Study

Background: Luminal B HER2-negative breast cancer responds only modestly to neoadjuvant chemotherapy (NAC), and the receptor profile of its residual tumor may differ from that of the original biopsy. Objective: To test whether subtype conversion after NAC is associated with pathological response. Methods: This retrospective cross-sectional study included 49 consecutive women with stage IIIA–IIIB Luminal B HER2-negative cancer who received doxorubicin–cyclophosphamide or docetaxel–cyclophosphamide before mastectomy at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia (2024–2025). Conversion meant any change in immunohistochemical surrogate subtype between core biopsy and mastectomy. The outcomes were the Miller–Payne grade (primary) and the Residual Cancer Burden (RCB) class. Exact tests, proportional-odds and Firth logistic regression, and Holm correction were applied. Results: Conversion occurred in 14 patients (28.6%; 95% CI 17.8–42.4), most often to Luminal B HER2-positive. Converted tumors had lower Miller–Payne grades (exact p = 0.027). None reached grade 4–5 (0/14 vs 9/35; p = 0.045). The adjusted cumulative odds ratio was 0.27 (95% CI 0.08–0.91). RCB-III was more frequent after conversion (78.6% vs 31.4%; adjusted OR 6.54, 95% CI 1.69–31.63). The association between conversion and the RCB class was the only one surviving Holm correction (p = 0.019), and the RCB-III association depended largely on eight HER2 gains defined by immunohistochemistry alone. Conclusion: More than one in four Luminal B HER2-negative tumors changed surrogate subtype after NAC. Conversion, mostly HER2 gain, marked heavier residual disease. Before adjuvant therapy is chosen, receptors should be re-tested on residual tumor, with in situ hybridization to confirm HER2.