title: First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations.
abstract: The aims of this study were to compare the performance of six different genomic prognostic markers to predict long-term survival and chemotherapy response on the same patient cohort and assess if clinicopathological variables carry independent prognostic and predictive values. We examined seven clinical variables and six previously described prognostic signatures on 228 tumors from patients who received homogeneous preoperative chemotherapy and had long-term follow-up information for survival. We used the area under the receiver operator characteristic curve (AUC) to compare predictors and also performed univariate and multivariate analyses including the genomic and clinical variables and plotted Kaplan-Meir survival curves. All genomic prognostic markers had statistically similar AUCs and sensitivity to predict 5-year progression-free survival (PFS, sensitivities ranged from 0.591 to 0.773, and AUCs: 0.599-0.673), overall survival (OS, sensitivities: 0.590-0.769, AUCs: 0.596-0.684) and pathologic complete response (pCR, sensitivities: 0.596-0.851, AUCs: 0.614-0.805). In multivariate analysis, the genomic markers were not independent from one another; however, estrogen receptor (Odds Ratio [OR] 7.63, P < 0.001) and HER2 status (OR: 0.37, P = 0.021) showed significant independent predictive values for pCR. Nodal status remained an independent prognostic, but not predictive, variable (OR for PFS: 2.77, P = 0.021, OR for OS: 3.62, P = 0.01). There was moderate to good agreement between different prediction results in pair-wise comparisons. First-generation prognostic-gene signatures predict both chemotherapy response and long-term survival. When multiple predictors are applied to the same case discordant risk prediction frequently occurs.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77230-1439, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bianchini
authors.forename: Rebekah E
authors.initials: RE
authors.lastname: Hubbard
authors.forename: Elliana
authors.initials: E
authors.lastname: Young
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012306:Risk; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor