title: The impact of genomic testing on the recommendation for radiation therapy in patients with ductal carcinoma in situ: A prospective clinical utility assessment of the 12-gene DCIS score™ result.
abstract: OBJECTIVE
  Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% having a local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX(®) 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians' recommendations for radiation.
  
  
  METHODS
  Ten sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known.
  
  
  RESULTS
  In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8 mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%CI: 49.6-68.2%) post-assay (P= 0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment.
  
  
  CONCLUSIONS
  The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%CI: 23.0-40.6%) of the time--a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.
authors.affiliation: University of California, San Francisco, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Alvarado
authors.affiliation: Rocky Mountain Cancer Centers, Aurora, Colorado.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Carter
authors.affiliation: St. Elizabeth Healthcare, Edgewood, Kentucky.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Guenther
authors.affiliation: The Surgical Center of Central Arkansas, Little Rock, Arkansas.
authors.forename: James
authors.initials: J
authors.lastname: Hagans
authors.affiliation: Rocky Mountain Cancer Centers, Aurora, Colorado.
authors.forename: Rachel Y
authors.initials: RY
authors.lastname: Lei
authors.affiliation: Rocky Mountain Cancer Centers, Littleton, Colorado.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Leonard
authors.affiliation: The Christ Hospital, Cincinnati, Ohio.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Manders
authors.affiliation: Genomic Health, Inc., Redwood City, California.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Sing
authors.affiliation: Partnership for Health Analytic Research, LLC, Beverly Hills, California.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Broder
authors.affiliation: Partnership for Health Analytic Research, LLC, Beverly Hills, California.
authors.forename: Dasha
authors.initials: D
authors.lastname: Cherepanov
authors.affiliation: Partnership for Health Analytic Research, LLC, Beverly Hills, California.
authors.forename: Eunice
authors.initials: E
authors.lastname: Chang
authors.affiliation: Partnership for Health Analytic Research, LLC, Beverly Hills, California.
authors.forename: Marianne
authors.initials: M
authors.lastname: Eagan
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Wendy
authors.initials: W
authors.lastname: Hsiao
authors.affiliation: University of Maryland St. Joseph Medical Center, Towson, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schultz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D018570:Risk Assessment
keywords: adjuvant radiotherapy; breast cancer; clinical utility; ductal carcinoma in situ; genomics; recurrence risk