Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker

نویسندگان

  • Dennis C. Sgroi
  • Erin Carney
  • Elizabeth Zarrella
  • Lauren Steffel
  • Shemeica N. Binns
  • Dianne M. Finkelstein
  • Jackie Szymonifka
  • Atul K. Bhan
  • Lois E. Shepherd
  • Yi Zhang
  • Catherine A. Schnabel
  • Mark G. Erlander
  • James N. Ingle
  • Peggy Porter
  • Hyman B. Muss
  • Katherine I. Pritchard
  • Dongsheng Tu
  • David L. Rimm
  • Paul E. Goss
چکیده

BACKGROUND Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole. METHODS A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided. RESULTS High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03). CONCLUSIONS In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.

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عنوان ژورنال:

دوره 105  شماره 

صفحات  -

تاریخ انتشار 2013