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

Published

Journal Article

AIMS: alphaB-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 alphaB-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. alphaB-crystallin expression was determined by immunohistochemistry in tissue microarrays. RESULTS: Seventeen percent of tumors were alphaB-crystallin positive. alphaB-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. alphaB-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as > or =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, alphaB-crystallin-positive tumors had poorer overall response rates than alphaB-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001). CONCLUSION: alphaB-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.

Full Text

Cited Authors

  • Ivanov, O; Chen, F; Wiley, EL; Keswani, A; Diaz, LK; Memmel, HC; Rademaker, A; Gradishar, WJ; Morrow, M; Khan, SA; Cryns, VL

Published Date

  • October 2008

Published In

Volume / Issue

  • 111 / 3

Start / End Page

  • 411 - 417

PubMed ID

  • 17968656

Pubmed Central ID

  • 17968656

Electronic International Standard Serial Number (EISSN)

  • 1573-7217

International Standard Serial Number (ISSN)

  • 0167-6806

Digital Object Identifier (DOI)

  • 10.1007/s10549-007-9796-0

Language

  • eng