Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response

PURPOSE: For patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT. METHODS: We assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens. RESULTS: ER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype. CONCLUSION: A patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.