title: Personalized chemotherapy selection for breast cancer using gene expression profiles.
abstract: Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens.
authors.affiliation: Department of Statistics, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Kaixian
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Chemistry &Biochemistry, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Qing-Xiang Amy
authors.initials: QA
authors.lastname: Sang
authors.affiliation: Department of Statistics, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Pei-Yau
authors.initials: PY
authors.lastname: Lung
authors.affiliation: Mayo clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Chemistry &Biochemistry, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Ty
authors.initials: T
authors.lastname: Lively
authors.affiliation: Department of Chemistry &Biochemistry, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Sheffield
authors.affiliation: Department of Chemistry &Biochemistry, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Mayassa J
authors.initials: MJ
authors.lastname: Bou-Dargham
authors.affiliation: Department of Statistics, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Statistics, Florida State University, Tallahassee, FL, 32306, USA.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D017239:Paclitaxel / Q000008:administration & dosage; D057285:Precision Medicine / Q000379:methods*; D043823:Taxoids / Q000008:administration & dosage; D059467:Transcriptome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel