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


CONCLUSIONS
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.
Ivanov
Olga
O
Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Chen
Feng
F
Wiley
Elizabeth L
EL
Keswani
Anjeni
A
Diaz
Leslie K
LK
Memmel
Heidi C
HC
Rademaker
Alfred
A
Gradishar
William J
WJ
Morrow
Monica
M
Khan
Seema A
SA
Cryns
Vincent L
VL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D017211:Treatment Failure; D038203:alpha-Crystallin B Chain / Q000032:analysis*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D038203:alpha-Crystallin B Chain; C508053:ERBB2 protein, human