Breast Cancer Research and Treatment

, Volume 111, Issue 3, pp 411–417

αB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer

  • Olga Ivanov
  • Feng Chen
  • Elizabeth L. Wiley
  • Anjeni Keswani
  • Leslie K. Diaz
  • Heidi C. Memmel
  • Alfred Rademaker
  • William J. Gradishar
  • Monica Morrow
  • Seema A. Khan
  • Vincent L. Cryns
Preclinical Study

DOI: 10.1007/s10549-007-9796-0

Cite this article as:
Ivanov, O., Chen, F., Wiley, E.L. et al. Breast Cancer Res Treat (2008) 111: 411. doi:10.1007/s10549-007-9796-0

Abstract

Aims αB-crystallin is an anti-apoptotic protein commonly expressed in poor prognosis basal-like breast tumors, which are largely triple (estrogen receptor (ER), progesterone receptor (PR), and HER2) negative. We examined whether αB-crystallin expression in breast cancer was associated with a poor response to neoadjuvant (preoperative) chemotherapy. Methods One hundred and twelve breast cancer patients who received neoadjuvant chemotherapy and who had post-chemotherapy tumor specimens available for analysis were included in the study. Forty-nine percent of patients were treated with doxorubicin and cyclophosphamide (AC), 37% received AC in combination with a taxane, and 14% received other regimens. Paired pre- and post-chemotherapy tumor specimens were available for 33 patients. αB-crystallin expression was determined by immunohistochemistry in tissue microarrays. Results Seventeen percent of tumors were αB-crystallin positive. αB-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. αB-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as ≥50% reduction in tumor size after treatment were 53% (clinical ORR) and 61% (pathological ORR). Although tumor grade, size, ER, PR, HER2 or triple negative status was not associated with response, αB-crystallin-positive tumors had poorer overall response rates than αB-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001). Conclusion αB-crystallin is a novel biomarker expressed predominantly in triple negative breast tumors that identifies a subset of chemotherapy-resistant tumors, which may contribute to their poor prognosis.

Keywords

αB-crystallin Chemotherapy Neoadjuvant Biomarker Apoptosis Breast cancer 

Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • Olga Ivanov
    • 1
  • Feng Chen
    • 2
  • Elizabeth L. Wiley
    • 3
  • Anjeni Keswani
    • 2
  • Leslie K. Diaz
    • 3
  • Heidi C. Memmel
    • 1
  • Alfred Rademaker
    • 4
  • William J. Gradishar
    • 2
  • Monica Morrow
    • 5
  • Seema A. Khan
    • 1
  • Vincent L. Cryns
    • 6
  1. 1.Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  3. 3.Department of Pathology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  4. 4.Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  5. 5.Department of Surgical OncologyFox Chase Cancer CenterPhiladelphiaUSA
  6. 6.Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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