Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome

Abstract

PURPOSE: The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications. MATERIALS AND METHODS: We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.