title: Unique molecular signatures as a hallmark of patients with metastatic breast cancer: implications for current treatment paradigms.
abstract: Our analysis of the tumors of 57 women with metastatic breast cancer with next generation sequencing (NGS) demonstrates that each patient's tumor is unique in its molecular fingerprint. We observed 216 somatic aberrations in 70 different genes, including 131 distinct aberrations. The most common gene alterations (in order of decreasing frequency) included: TP53, PIK3CA, CCND1, MYC, HER2 (ERBB2), MCL1, PTEN, FGFR1, GATA3, NF1, PIK3R1, BRCA2, EGFR, IRS2, CDH1, CDKN2A, FGF19, FGF3 and FGF4. Aberrations included mutations (46%), amplifications (45%), deletions (5%), splices (2%), truncations (1%), fusions (0.5%) and rearrangements (0.5%), with multiple distinct variants within the same gene. Many of these aberrations represent druggable targets, either through direct pathway inhibition or through an associated pathway (via 'crosstalk'). The 'molecular individuality' of these tumors suggests that a customized strategy, using an "N-of-One" model of precision medicine, may represent an optimal approach for the treatment of patients with advanced tumors.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Parker
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Johnique T
authors.initials: JT
authors.lastname: Atkins
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Ralph
authors.initials: R
authors.lastname: Zinner
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.forename: Stacy
authors.initials: S
authors.lastname: Moulder
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Maria
authors.initials: M
authors.lastname: Schwaederle
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: M Philip J
authors.initials: MP
authors.lastname: Stephens
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D052138:Genes, Neoplasm; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins