title: Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.
abstract: Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents.
authors.affiliation: University of Padua, School of Medicine, Department of Surgery, Oncology and Gastroenterology (DiSCOG), Padova, Italy flumachi@unipd.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Lumachi
authors.affiliation: Surgery 1, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Giordano B
authors.initials: GB
authors.lastname: Chiara
authors.affiliation: Medical Oncology, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Foltran
authors.affiliation: Surgery 1, S. Maria degli Angeli Hospital, Pordenone, Italy.
authors.forename: Stefano M M
authors.initials: SM
authors.lastname: Basso
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000627:therapeutic use; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A; C499320:PARP1 protein, human; C546842:MTOR protein, human; C508053:ERBB2 protein, human
keywords: HER2; Proteomics; VEGF; breast cancer; early breast cancer; genomics; mTOR; review; targeted therapies; trastuzumab; triple-negative