Alterations of biomarker profiles after neoadjuvant chemotherapy in breast cancer: tumor heterogeneity should be taken into consideration

// Xingchen Zhou 1, * , Junyong Zhang 2, * , Haiqin Yun 1 , Ranran Shi 1 , Yan Wang 1 , Wei Wang 3 , Svetlana Bajalica Lagercrantz 4 , Kun Mu 1 1 Department of Pathology, Shandong University School of Medicine, Jinan 250012, China 2 Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China 3 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 4 Department of Oncology-Pathology, Karolinska Institutet, CCK Karolinska University Hospital, Stockholm SE-171 76, Sweden * These authors have contributed equally to this work Correspondence to: Kun Mu, e-mail: mukun@sdu.edu.cn Keywords: breast cancer, neoadjuvant chemotherapy, biomarkers, heterogeneity Received: May 31, 2015 Accepted: August 25, 2015 Published: September 05, 2015 ABSTRACT Tumor biomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 are routinely tested in breast cancer patients and their status guides clinical management and predicts prognosis. A few retrospective studies have suggested that neoadjuvant chemotherapy (NAC) in breast cancer may change the status of biomarker expression, which in turn will affect further management of these patients. In this study we take advantage of a relatively large cohort and aim to study the effect of NAC on biomarker expression and explore the impact of tumor size and lymph node involvement on biomarker status changes. We collected 107 patients with invasive breast cancer who received at least three cycles of NAC. We retrospectively performed and scored the immunohistochemistry (IHC) of ER, PR, HER2 and Ki-67 using both the diagnostic core biopsies before NAC and excisional specimens following NAC. HER2 gene status was assessed by fluorescence in situ hybridization for cases with IHC result of 2+. We demonstrated that there was a significant decrease in expression of PR ( P = 0.013) and Ki-67 ( P = 0.000) in post-NAC specimens compared to pre-NAC core biopsies. In addition, cases with large tumor size (≥2cm) and cases with lymph node metastasis were more frequently to have biomarker changes. Finally we studied cases with HER2 status changes after NAC treatments in detail and emphasized the nature of tumor heterogeneity.