Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
OBJECTIVE
The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known.


METHODS
The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS.


RESULTS
A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit.


CONCLUSIONS
The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
Paik
Soonmyung
S
Division of Pathology, Operations Center, and Biostatistical Center, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212, USA. soon.paik@nsabp.org
Tang
Gong
G
Shak
Steven
S
Kim
Chungyeul
C
Baker
Joffre
J
Kim
Wanseop
W
Cronin
Maureen
M
Baehner
Frederick L
FL
Watson
Drew
D
Bryant
John
J
Costantino
Joseph P
JP
Geyer
Charles E
CE
Wickerham
D Lawrence
DL
Wolmark
Norman
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016014:Linear Models; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D013629:Tamoxifen / Q000008:administration & dosage
D014408:Biomarkers, Tumor; D008937:Mitomycins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate