Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial.
OBJECTIVE
To investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen.


METHODS
Pathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative, HER2/neu [HER2]-negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67(high)), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67(high)), and assessed for prognostic significance and response to adjuvant chemotherapy.


RESULTS
Patients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population.


CONCLUSIONS
A simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population.
Hugh
Judith
J
Department of Lab Medicine and Pathology, University of Alberta Hospital, 8440 112th St, Edmonton, Alberta, Canada T6G 2B7. judith.hugh@capitalhealth.ca
Hanson
John
J
Cheang
Maggie Chon U
MC
Nielsen
Torsten O
TO
Perou
Charles M
CM
Dumontet
Charles
C
Reed
John
J
Krajewska
Maryla
M
Treilleux
Isabelle
I
Rupin
Matthieu
M
Magherini
Emmanuelle
E
Mackey
John
J
Martin
Miguel
M
Vogel
Charles
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage*
D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; D043823:Taxoids; C508053:ERBB2 protein, human