title: Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657).
abstract: Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
authors.affiliation: University of California San Francisco, 1600 Divisadero Street, Box 1710, San Francisco, CA 94115, USA. Laura.esserman@ucsfmedctr.org
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Esserman
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Maggie C U
authors.initials: MC
authors.lastname: Cheang
authors.forename: Christina
authors.initials: C
authors.lastname: Yau
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Lisa
authors.initials: L
authors.lastname: Carey
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.forename: Joe W
authors.initials: JW
authors.lastname: Gray
authors.forename: Kathleen
authors.initials: K
authors.lastname: Conway-Dorsey
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.forename: Meredith B
authors.initials: MB
authors.lastname: Buxton
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Davis
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Koei
authors.initials: K
authors.lastname: Chin
authors.forename: Denise
authors.initials: D
authors.lastname: Wolf
authors.forename: Helen
authors.initials: H
authors.lastname: Krontiras
authors.forename: Leslie
authors.initials: L
authors.lastname: Montgomery
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Constance
authors.initials: C
authors.lastname: Lehman
authors.forename: Minetta C
authors.initials: MC
authors.lastname: Liu
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: John T
authors.initials: JT
authors.lastname: Carpenter
authors.forename: Chad
authors.initials: C
authors.lastname: Livasy
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: David
authors.initials: D
authors.lastname: Chhieng
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.forename: Carolyn
authors.initials: C
authors.lastname: Mies
authors.forename: Joseph
authors.initials: J
authors.lastname: Rabban
authors.forename: Yunni-Yi
authors.initials: YY
authors.lastname: Chen
authors.forename: Dilip
authors.initials: D
authors.lastname: Giri
authors.forename: Alfred
authors.initials: A
authors.lastname: Au
authors.forename: Nola
authors.initials: N
authors.lastname: Hylton
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D016016:Proportional Hazards Models; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D011987:Receptors, Steroid; D043823:Taxoids; D000068878:Trastuzumab