Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1036-1042
Number of pages7
JournalJournal of the National Cancer Institute
Volume105
Issue number14
DOIs
StatePublished - Jul 17 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sgroi, D. C., Carney, E., Zarrella, E., Steffel, L., Binns, S. N., Finkelstein, D. M., Szymonifka, J., Bhan, A. K., Shepherd, L. E., Zhang, Y., Schnabel, C. A., Erlander, M. G., Ingle, J. N., Porter, P., Muss, H. B., Pritchard, K. I., Tu, D., Rimm, D. L., & Goss, P. E. (2013). Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. Journal of the National Cancer Institute, 105(14), 1036-1042. https://doi.org/10.1093/jnci/djt146