Cancer Causes & Control

, Volume 30, Issue 1, pp 41–51 | Cite as

Potential protein markers for breast cancer recurrence: a retrospective cohort study

  • Chunyan HeEmail author
  • Rina Plattner
  • Vivek Rangnekar
  • Binhua Zhou
  • Chunming Liu
  • Rachel L. Stewart
  • Bin Huang
  • Chi Wang
  • Thomas C. TuckerEmail author
Original paper



We evaluated five key proteins involved in various cancer-related pathways and assessed their relation to breast cancer recurrence.


We used the Kentucky Cancer Registry to retrospectively identify primary invasive breast cancer cases (n = 475) that were diagnosed and treated at University of Kentucky Medical Center between 2000 and 2007. Breast cancer recurrence was observed in 62 cases during the 5-year follow-up after diagnosis. Protein expression or activity level was analyzed from surgery tissue using immuno-histochemical assays.


Compared to ER+/PR+/HER2− patients without recurrence, those with recurrence had higher TWIST expression (p = 0.049) but lower ABL1/ABL2 activity (p = 0.003) in primary tumors. We also found that triple-negative breast cancer patients with recurrence had higher SNAI1 expression compared to those without recurrence (p = 0.03). After adjusting for potential confounders, the higher ABL1/ABL2 activity in primary tumors was associated with a decreased risk of recurrence (OR 0.72, 95% CI 0.85–0.90) among ER+/PR+/HER2− patients. In addition, among patients with recurrence we observed that the activity level of ABL1/ABL2 was significantly increased in recurrent tumors compared to the matched primary tumors regardless of the subtype (p = 0.013).


These findings provide evidence that the expression/activity level of various proteins may be differentially associated with risk of recurrence of breast tumor subtypes.


Breast cancer Recurrence Biomarkers Protein expression Protein activity Tumor subtypes 



Special thanks to Dana Napier for her expertise in TMA construction and talent with immunohistochemistry. Drs. He, Plattner, Rangnekar, Zhou, and Tucker are supported by the University of Kentucky Markey Cancer Center (P30CA177558). Dr. Stewart is supported by NIH fellowship Grant T32 CA160003. The Markey Cancer Center’s Research Communications Office assisted with preparation of this manuscript.


This research project was supported by Markey Cancer Center pilot funding IRB# 14-0172-P3H, the Biospecimen Procurement and Translational Pathology, the Biostatistics and Bioinformatics, and the Cancer Research Informatics Shared Resource Facilities of the University of Kentucky Markey Cancer Center (P30CA177558).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

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Supplementary material 1 (PDF 125 KB)
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Supplementary material 3 (PDF 1640 KB)
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Supplementary material 4 (DOCX 649 KB)
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Supplementary material 5 (DOCX 16 KB)


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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  2. 2.Department of Internal Medicine, Division of Medical Oncology, College of MedicineUniversity of KentuckyLexingtonUSA
  3. 3.Department of Pharmacology and Nutritional Sciences, College of MedicineUniversity of KentuckyLexingtonUSA
  4. 4.Department of Molecular and Cellular Biochemistry, College of MedicineUniversity of KentuckyLexingtonUSA
  5. 5.Department of Radiation Medicine, College of MedicineUniversity of KentuckyLexingtonUSA
  6. 6.Department of Pathology and Laboratory Medicine, College of MedicineUniversity of KentuckyLexingtonUSA
  7. 7.Department of Biostatistics, College of Public HealthUniversity of KentuckyLexingtonUSA
  8. 8.Department of Epidemiology, College of Public HealthUniversity of KentuckyLexingtonUSA
  9. 9.Markey Cancer CenterUniversity of KentuckyLexingtonUSA

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