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, 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
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.
Figures
References
- Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–1717
- Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349:1793–1802
- Jin H, Tu D, Zhao N, et al. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2011;30:718–721
- Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010;28:3784–3796
- Carlson RW, Allred DC, Anderson BO. et al. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines, Breast Cancer. 2011. J Natl Compr Cancer Netw. 2011;9:136–222
- Goss PE. Letrozole in the extended adjuvant setting: MA.17. Breast Cancer Res Treat. 2007;105(Suppl 1):45–53
- Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11:55–65
- Cardoso F, Van’t Veer L, Rutgers E, et al. Clinical application of the 70-gene profile: the MINDACT trial. J Clin Oncol. 2008;26:729–735
- Burstein HJ, Griggs JJ. Deep time: the long and the short of adjuvant endocrine therapy for breast cancer. J Clin Oncol. 2012;30:684–686
- Goetz MP, Suman VJ, Ingle JN, et al. A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen. Clin Cancer Res. 2006;12:2080–2087
- Ma XJ, Hilsenbeck SG, Wang W, et al. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol. 2006;24:4611–4619
- Ma XJ, Salunga R, Dahiya S, et al. A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res. 2008;14:2601–2608
- Ma XJ, Wang Z, Ryan PD, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 2004;5:607–616
- Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst. 2009;101:1446–1152
- Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–2795
- Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43
- Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models. Biom J. 2008;50:346–363
- Langholz B, Borgan O. Estimation of absolute risk from nested case-control data. Biometrics. 1997;53:767–774
- Devlin TF, Weeks BJ. Spline functions for logistic regression modeling. Proceedings of the 11th Annual SAS Users Group International Conference. Cary, NC: SAS Institute; 1986:646–651
- Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005;97:1262–1271
- Dent SF, Gaspo R, Kissner M, et al. Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res Treat. 2011;126:295–310
- Partridge AH, LaFountain A, Mayer E, et al. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008;26:556–562
- Verma S, Madarnas Y, Sehdev S, et al. Patient adherence to aromatase inhibitor treatment in the adjuvant setting. Curr Oncol. 2011;18(Suppl 1):S3–S9
- Myrick ME, Schmid SM, Kilic N, et al. Eligibility, compliance and persistence of extended adjuvant endocrine therapy for breast cancer. Acta Oncol. 2011;51:247–253
- Goss PE, Ingle JN, Pater JL, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008;26:1948–1955
- Goss PE, Muss HB, Ingle JN, et al. Extended adjuvant endocrine therapy in breast cancer: current status and future directions. Clin Breast Cancer. 2008;8:411–417
Source: PubMed