Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer

PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. MATERIALS AND METHODS: The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.