title: A systematic evaluation of multi-gene predictors for the pathological response of breast cancer patients to chemotherapy.
abstract: Previous studies have reported conflicting assessments of the ability of cell line-derived multi-gene predictors (MGPs) to forecast patient clinical outcomes in cancer patients, thereby warranting an investigation into their suitability for this task. Here, 42 breast cancer cell lines were evaluated by chemoresponse tests after treatment with either TFAC or FEC, two widely used standard combination chemotherapies for breast cancer. We used two different training cell line sets and two independent prediction methods, superPC and COXEN, to develop cell line-based MGPs, which were then validated in five patient cohorts treated with these chemotherapies. This evaluation yielded high prediction performances by these MGPs, regardless of the training set, chemotherapy, or prediction method. The MGPs were also able to predict patient clinical outcomes for the subgroup of estrogen receptor (ER)-negative patients, which has proven difficult in the past. These results demonstrated a potential of using an in vitro-based chemoresponse data as a model system in creating MGPs for stratifying patients' therapeutic responses. Clinical utility and applications of these MGPs will need to be carefully examined with relevant clinical outcome measurements and constraints in practical use.
authors.affiliation: Precision Therapeutics, Inc., Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kui
authors.initials: K
authors.lastname: Shen
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.forename: Youngchul
authors.initials: Y
authors.lastname: Kim
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Shara D
authors.initials: SD
authors.lastname: Rice
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gabrin
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D020869:Gene Expression Profiling; D006801:Humans; D015233:Models, Statistical; D010597:Pharmacogenetics; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil