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. 2015 Nov 3;6(34):36894-902.
doi: 10.18632/oncotarget.5050.

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
Affiliations

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

Xingchen Zhou et al. Oncotarget. .

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 (≥ 2 cm) 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.

Keywords: biomarkers; breast cancer; heterogeneity; neoadjuvant chemotherapy.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Paired analysis of biomarker changes after NAC
PR expression and Ki-67 index were significantly decreased in post-NAC excisional specimens when compared to pre-NAC core biopsies (*P < 0.05, ***P < 0.001, NS: No significant difference).
Figure 2
Figure 2. IHC of case QL25 demonstrated tumor heterogeneity and altered biomarker expression patterns after NAC treatment
In the core biopsy (left), there are areas with HER2 IHC2+ and adjacent areas with IHC3+. In the IHC2+ regions, ER positivity was moderate, along with weak PR expression and relatively low Ki-67 index (25%); in the IHC3+ areas, ER positivity was weak, PR was negative, and Ki-67 index was 45%. After NAC (right), HER2 was changed to 1+, along with strong ER expression and moderate PR positivity. The Ki67 index was 35%.
Figure 3
Figure 3. FISH study of breast carcinoma from case QL25 showing HER2 heterogeneity and status change after NAC treatment
FISH demonstrated obvious tumor heterogeneity with HER2 dot amplification (HER2/CEP17 ratio = 3) A. and adjacent cluster amplification B. in pre-NAC core biopsy. After NAC treatment, HER2 was changed to negative (HER2/CEP17 ratio = 1.41) C.
See this image and copyright information in PMC

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