Clinical Research Papers:

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

Xingchen Zhou _, Junyong Zhang, Haiqin Yun, Ranran Shi, Yan Wang, Wei Wang, Svetlana Bajalica Lagercrantz and Kun Mu

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Oncotarget. 2015; 6:36894-36902. https://doi.org/10.18632/oncotarget.5050

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Xingchen Zhou1,*, Junyong Zhang2,*, Haiqin Yun1, Ranran Shi1, Yan Wang1, Wei Wang3, Svetlana Bajalica Lagercrantz4, Kun Mu1

1Department of Pathology, Shandong University School of Medicine, Jinan 250012, China

2Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China

3Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

4Department 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: [email protected]

Keywords: breast cancer, neoadjuvant chemotherapy, biomarkers, heterogeneity

Received: May 31, 2015     Accepted: August 25, 2015     Published: September 05, 2015


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.

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