Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

Norman Wolmark ¹, Eleftherios P Mamounas ², Frederick L Baehner ¹, Steven M Butler ¹, Gong Tang ¹, Farid Jamshidian ¹, Amy P Sing ¹, Steven Shak ¹, Soonmyung Paik ¹

Affiliations

¹ Norman Wolmark, Eleftherios P. Mamounas, and Soonmyung Paik, National Surgical Adjuvant Breast and Bowel Project Operations Center; Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Gong Tang, University of Pittsburgh; and Gong Tang, NRG Oncology, Pittsburgh, PA; Eleftherios P. Mamounas, UF Health Cancer Center at Orlando Health, Orlando, FL; Frederick L. Baehner, Steven M. Butler, Farid Jamshidian, Amy P. Sing, and Steven Shak, Genomic Health, Redwood City, and Frederick L. Baehner, University of California, San Francisco, San Francisco CA; and Soonmyung Paik, Yonsei University College of Medicine, Seoul, Korea.
² Norman Wolmark, Eleftherios P. Mamounas, and Soonmyung Paik, National Surgical Adjuvant Breast and Bowel Project Operations Center; Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Gong Tang, University of Pittsburgh; and Gong Tang, NRG Oncology, Pittsburgh, PA; Eleftherios P. Mamounas, UF Health Cancer Center at Orlando Health, Orlando, FL; Frederick L. Baehner, Steven M. Butler, Farid Jamshidian, Amy P. Sing, and Steven Shak, Genomic Health, Redwood City, and Frederick L. Baehner, University of California, San Francisco, San Francisco CA; and Soonmyung Paik, Yonsei University College of Medicine, Seoul, Korea. terry.mamounas@orlandohealth.com.

PMID: 27217450
31 References
22 citations

Abstract

Purpose: We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups.

Patients And Methods: RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14.

Results: Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01).

Conclusion: For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis.

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References
Cited By

References
Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Maureen Cronin, Chithra Sangli, +7 authors, Drew Watson. less Clin Chem, 2007 Apr 28; 53(6). PMID: 17463177 Highly Cited.
Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers. Giampaolo Bianchini, Lajos Pusztai, +16 authors, Luca Gianni. less Breast Cancer Res, 2013 Sep 26; 15(5). PMID: 24060333 Free PMC article.
Biologic markers determine both the risk and the timing of recurrence in breast cancer. Laura J Esserman, Dan H Moore, +11 authors, Christopher C Benz. less Breast Cancer Res Treat, 2011 May 21; 129(2). PMID: 21597921 Free PMC article.
The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Martin Filipits, Torsten O Nielsen, +22 authors, Austrian Breast and Colorectal Cancer Study Group. less Clin Cancer Res, 2014 Feb 13; 20(5). PMID: 24520097
Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. Mitch Dowsett, Ivana Sestak, +7 authors, Jack Cuzick. less J Clin Oncol, 2013 Jul 03; 31(22). PMID: 23816962 Highly Cited.
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), C Davies, +11 authors, R Peto. less Lancet, 2011 Aug 02; 378(9793). PMID: 21802721 Free PMC article. Highly Cited.
Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. Mitch Dowsett, Jack Cuzick, +11 authors, Steven Shak. less J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256 Highly Cited.
Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. Fiona M Blows, Kristy E Driver, +40 authors, David Huntsman. less PLoS Med, 2010 Jun 04; 7(5). PMID: 20520800 Free PMC article. Highly Cited.
Residual risk of breast cancer recurrence 5 years after adjuvant therapy. Abenaa M Brewster, Gabriel N Hortobagyi, +8 authors, Francisco J Esteva. less J Natl Cancer Inst, 2008 Aug 13; 100(16). PMID: 18695137 Free PMC article. Highly Cited.
A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Torsten O Nielsen, Joel S Parker, +12 authors, Matthew J Ellis. less Clin Cancer Res, 2010 Sep 15; 16(21). PMID: 20837693 Free PMC article. Highly Cited.
Estrogen Receptor Expression in 21-Gene Recurrence Score Predicts Increased Late Recurrence for Estrogen-Positive/HER2-Negative Breast Cancer. Mitch Dowsett, Ivana Sestak, +6 authors, Jack Cuzick. less Clin Cancer Res, 2015 Jun 17; 21(12). PMID: 26078431
Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. Eleftherios P Mamounas, John Bryant, +7 authors, Norman Wolmark. less J Clin Oncol, 2005 May 18; 23(16). PMID: 15897552 Highly Cited.
Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. Dennis C Sgroi, Erin Carney, +16 authors, Paul E Goss. less J Natl Cancer Inst, 2013 Jul 03; 105(14). PMID: 23812955 Free PMC article.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark. less J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680 Highly Cited.
Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Dennis C Sgroi, Ivana Sestak, +9 authors, Mitch Dowsett. less Lancet Oncol, 2013 Sep 17; 14(11). PMID: 24035531 Free PMC article. Highly Cited.
Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer. Arran K Turnbull, Laura M Arthur, +7 authors, J Michael Dixon. less J Clin Oncol, 2015 Jun 03; 33(20). PMID: 26033813
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark. less N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335 Highly Cited.
Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Christina Davies, Hongchao Pan, +36 authors, Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. less Lancet, 2012 Dec 12; 381(9869). PMID: 23219286 Free PMC article. Highly Cited.
A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. B Fisher, J Costantino, +7 authors, E R Fisher. less N Engl J Med, 1989 Feb 23; 320(8). PMID: 2644532 Highly Cited.
The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. P Dubsky, J C Brase, +18 authors, Austrian Breast and Colorectal Cancer Study Group (ABCSG). less Br J Cancer, 2013 Oct 26; 109(12). PMID: 24157828 Free PMC article. Highly Cited.
Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. Harold J Burstein, Sarah Temin, +10 authors, Jennifer J Griggs. less J Clin Oncol, 2014 May 29; 32(21). PMID: 24868023 Free PMC article. Highly Cited.
Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. Sunil S Badve, Frederick L Baehner, +13 authors, Joseph A Sparano. less J Clin Oncol, 2008 May 20; 26(15). PMID: 18487567
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. Kathy S Albain, William E Barlow, +20 authors, Breast Cancer Intergroup of North America. less Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174 Free PMC article. Highly Cited.
Factors predicting late recurrence for estrogen receptor-positive breast cancer. Ivana Sestak, Mitch Dowsett, +4 authors, Jack Cuzick. less J Natl Cancer Inst, 2013 Sep 14; 105(19). PMID: 24029245 Free PMC article. Highly Cited.
Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. B Fisher, J Dignam, +18 authors, H L Lickley. less J Natl Cancer Inst, 1996 Nov 06; 88(21). PMID: 8901851 Highly Cited.
Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. Lori J Goldstein, Robert Gray, +12 authors, Joseph A Sparano. less J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838 Free PMC article. Highly Cited.
Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. B Fisher, J Dignam, J Bryant, N Wolmark. J Natl Cancer Inst, 2001 May 03; 93(9). PMID: 11333290
Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer. Chungyeul Kim, Gong Tang, +18 authors, Soonmyung Paik. less J Clin Oncol, 2011 Sep 29; 29(31). PMID: 21947828 Free PMC article.
Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. Ivana Sestak, Jack Cuzick, +8 authors, Michael Gnant. less J Clin Oncol, 2014 Oct 22; 33(8). PMID: 25332252 Highly Cited.
Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. Paul E Goss, James N Ingle, +15 authors, Dongsheng Tu. less J Clin Oncol, 2008 Mar 12; 26(12). PMID: 18332475
Annual hazard rates of recurrence for breast cancer after primary therapy. T Saphner, D C Tormey, R Gray. J Clin Oncol, 1996 Oct 01; 14(10). PMID: 8874335 Highly Cited.

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Extended Endocrine Therapy: Is 5 Years Enough? Manali A Bhave, N Lynn Henry. Curr Oncol Rep, 2017 Mar 03; 19(3). PMID: 28251491 Review.
An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®. Zsuzsanna Varga, Annette Lebeau, +18 authors, Giuseppe Viale. less Breast Cancer Res, 2017 May 12; 19(1). PMID: 28490348 Free PMC article.
Identifying Biomarkers to Select Patients with Early Breast Cancer Suitable for Extended Adjuvant Endocrine Therapy. Ivana Sestak. Breast Care (Basel), 2017 Aug 09; 12(3). PMID: 28785181 Free PMC article. Review.
Extended Adjuvant Endocrine Therapy for Postmenopausal Women: Treating Many to Benefit a Few. Paula R Pohlmann, Claudine Isaacs. J Natl Cancer Inst, 2017 Sep 20; 110(1). PMID: 28922782 Free PMC article.
Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer. Volker Möbus, Susanne Hell, Marcus Schmidt. Geburtshilfe Frauenheilkd, 2017 Nov 03; 77(10). PMID: 29093601 Free PMC article.
20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. Hongchao Pan, Richard Gray, +9 authors, EBCTCG. less N Engl J Med, 2017 Nov 09; 377(19). PMID: 29117498 Free PMC article. Highly Cited.
Optimal duration of adjuvant endocrine therapy: how to apply the newest data. Kerstin Wimmer, Stephanie Strobl, +5 authors, Michael Gnant. less Ther Adv Med Oncol, 2018 Jan 19; 9(11). PMID: 29344105 Free PMC article. Review.
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Ivana Sestak, Richard Buus, +9 authors, Mitch Dowsett. less JAMA Oncol, 2018 Feb 17; 4(4). PMID: 29450494 Free PMC article. Highly Cited.
Differential microRNA expression profiles in tamoxifen-resistant human breast cancer cell lines induced by two methods. Peng Ye, Cheng Fang, +6 authors, Xinghua Long. less Oncol Lett, 2018 Feb 23; 15(3). PMID: 29467872 Free PMC article.
Luminal A Breast Cancer and Molecular Assays: A Review. Jennifer J Gao, Sandra M Swain. Oncologist, 2018 Feb 24; 23(5). PMID: 29472313 Free PMC article. Review.
The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial). Frédérique Penault-Llorca, Thomas Filleron, +12 authors, Henri Roché. less BMC Cancer, 2018 May 08; 18(1). PMID: 29728098 Free PMC article.
Optimal management of luminal breast cancer: how much endocrine therapy is long enough? Elisabetta Munzone, Marco Colleoni. Ther Adv Med Oncol, 2018 Jul 07; 10. PMID: 29977350 Free PMC article. Review.
Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer. Richard Buus, Belinda Yeo, +7 authors, Mitch Dowsett. less Breast Cancer Res, 2018 Sep 06; 20(1). PMID: 30180877 Free PMC article.
Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy. Salomon M Stemmer, Mariana Steiner, +16 authors, David B Geffen. less NPJ Breast Cancer, 2019 Nov 16; 5. PMID: 31728408 Free PMC article.
Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help? Marie Alexandre, Aurélie Maran-Gonzalez, +6 authors, Séverine Guiu. less Cancer Manag Res, 2019 Dec 19; 11. PMID: 31849525 Free PMC article. Review.
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge. less N Engl J Med, 2019 Jun 04; 380(25). PMID: 31157962 Free PMC article. Highly Cited.
Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer. Jinani Jayasekera, Yisheng Li, +21 authors, CISNET-BOLD Collaborative Group. less J Natl Cancer Inst, 2018 May 03; 110(12). PMID: 29718314 Free PMC article.
Association of Circulating Tumor Cells With Late Recurrence of Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Joseph Sparano, Anne O'Neill, +5 authors, Kathy D Miller. less JAMA Oncol, 2018 Jul 29; 4(12). PMID: 30054636 Free PMC article. Highly Cited.
Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Eleftherios P Mamounas, Hanna Bandos, +17 authors, Norman Wolmark. less Lancet Oncol, 2018 Dec 05; 20(1). PMID: 30509771 Free PMC article.
Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 1: Late Recurrence: Current Understanding, Clinical Considerations. Ryan J O Dowling, Kevin Kalinsky, +29 authors, Pamela J Goodwin. less JNCI Cancer Spectr, 2020 Apr 28; 3(4). PMID: 32337479 Free PMC article.
21-Gene Recurrence Score Assay Could Not Predict Benefit of Post-mastectomy Radiotherapy in T1-2 N1mic ER-Positive HER2-Negative Breast Cancer. Wen-Wen Zhang, Qin Tong, +8 authors, Huan-Xin Lin. less Front Oncol, 2019 May 02; 9. PMID: 31041190 Free PMC article.
Clinical utility of genomic signatures in young breast cancer patients: a systematic review. Cynthia Villarreal-Garza, Ana S Ferrigno, +3 authors, Hatem A Azim. less NPJ Breast Cancer, 2020 Oct 17; 6. PMID: 33062888 Free PMC article. Review.

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