title: Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood.
abstract: OBJECTIVE
  We sought to evaluate the feasibility of detecting PIK3CA mutations in circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast cancer using a novel technique called BEAMing.
  
  
  METHODS
  In a retrospective analysis, 49 tumor and temporally matched plasma samples from patients with breast cancer were screened for PIK3CA mutations by BEAMing. We then prospectively screened the ctDNA of 60 patients with metastatic breast cancer for PIK3CA mutations by BEAMing and compared the findings with results obtained by screening corresponding archival tumor tissue DNA using both sequencing and BEAMing.
  
  
  RESULTS
  The overall frequency of PIK3CA mutations by BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the retrospective cohort, the concordance of PIK3CA mutation status by BEAMing between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from temporally matched plasma was 100% (34 of 34). In the prospective cohort, the concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and sequencing of archival tumor tissue DNA. When the same archival tissue DNA was screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue samples), there was 100% concordance in the obtained results.
  
  
  CONCLUSIONS
  Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in patients with metastatic breast cancer is feasible. Our results suggest that PIK3CA mutational status can change upon disease recurrence, emphasizing the importance of reassessing PIK3CA status on contemporary (not archival) biospecimens. These results have implications for the development of predictive biomarkers of response to targeted therapies.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Michaela J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Danijela
authors.initials: D
authors.lastname: Jelovac
authors.forename: Evan
authors.initials: E
authors.lastname: Barnathan
authors.forename: Brian
authors.initials: B
authors.lastname: Blair
authors.forename: Shannon
authors.initials: S
authors.lastname: Slater
authors.forename: Penny
authors.initials: P
authors.lastname: Powers
authors.forename: Jane
authors.initials: J
authors.lastname: Zorzi
authors.forename: Stacie C
authors.initials: SC
authors.lastname: Jeter
authors.forename: George R
authors.initials: GR
authors.lastname: Oliver
authors.forename: John
authors.initials: J
authors.lastname: Fetting
authors.forename: Leisha
authors.initials: L
authors.lastname: Emens
authors.forename: Carol
authors.initials: C
authors.lastname: Riley
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.forename: Frank
authors.initials: F
authors.lastname: Diehl
authors.forename: Philipp
authors.initials: P
authors.lastname: Angenendt
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Kurtis E
authors.initials: KE
authors.lastname: Bachman
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Ben H
authors.initials: BH
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood* / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human