Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry

Salomon M Stemmer ¹, Mariana Steiner ², Shulamith Rizel ¹, Lior Soussan-Gutman ³, Noa Ben-Baruch ⁴, Avital Bareket-Samish ⁵, David B Geffen ⁶, Bella Nisenbaum ⁷, Kevin Isaacs ⁸, Georgeta Fried ⁹, Ora Rosengarten ¹⁰, Beatrice Uziely ¹¹, Christer Svedman ¹², Debbie McCullough ¹², Tara Maddala ¹², Shmuel H Klang ¹³, Jamal Zidan ¹⁴, Larisa Ryvo ¹⁵, Bella Kaufman ¹⁶, Ella Evron ¹⁶, Natalya Karminsky ¹⁷, Hadassah Goldberg ¹⁸, Steven Shak ¹², Nicky Liebermann ¹³

Affiliations

¹ Davidoff Center, Rabin Medical Center, 39 Jabotinski St., Petah Tikva, 49414 Israel.
² Lin Medical Center, Haifa, Israel.
³ Oncotest Division, Teva Pharmaceutical Industries, Ltd., Shoham, Israel.
⁴ Oncology Dept., Kaplan Medical Center, Rehovot, Israel.
⁵ BioInsight Ltd, Zichron Yaakov, Israel.
⁶ Department of Oncology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
⁷ Oncology Dept., Meir Medical Center, Kfar Saba, Israel.
⁸ Oncology Dept., Ha'emek Medical Center, Afula, Israel.
⁹ Oncology Dept., Rambam Health Care Campus, Haifa, Israel.
¹⁰ Oncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
¹¹ Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
¹² Genomic Health Inc., Redwood City, CA USA.
¹³ Community Division, Clalit Health Services, Tel Aviv, Israel.
¹⁴ Oncology Dept., Ziv Medical Center, Safed, Israel.
¹⁵ Oncology Dept., Tel-Aviv Sourasky Medical center, Tel Aviv, Israel.
¹⁶ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹⁷ Oncology Dept., Wolfson Medical Center, Holon, Israel.
¹⁸ Faculty of Medicine, Bar Ilan University, Safed, Israel.

PMID: 28900633
27 References
20 citations

Abstract

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

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References
Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. A S Coates, E P Winer, +6 authors, Panel Members. less Ann Oncol, 2015 May 06; 26(8). PMID: 25939896 Free PMC article. Highly Cited.
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.
A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Laurel A Habel, Steven Shak, +12 authors, Charles P Quesenberry. less Breast Cancer Res, 2006 Jun 02; 8(3). PMID: 16737553 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.
A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Martin Filipits, Margaretha Rudas, +25 authors, EP Investigators. less Clin Cancer Res, 2011 Aug 03; 17(18). PMID: 21807638 Highly Cited.
Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. M Gnant, M Filipits, +22 authors, Austrian Breast and Colorectal Cancer Study Group. less Ann Oncol, 2013 Dec 19; 25(2). PMID: 24347518 Highly Cited.
Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. Valentina I Petkov, Dave P Miller, +21 authors, Steven Shak. less NPJ Breast Cancer, 2017 Jul 20; 2. PMID: 28721379 Free PMC article. Highly Cited.
Prospective study of the effect of the 21-gene assay on adjuvant clinical decision-making in Japanese women with estrogen receptor-positive, node-negative, and node-positive breast cancer. Hideko Yamauchi, Chizuko Nakagawa, +7 authors, Seigo Nakamura. less Clin Breast Cancer, 2013 Dec 11; 14(3). PMID: 24321102
The impact of the Oncotype DX Recurrence Score on treatment decisions and clinical outcomes in patients with early breast cancer: the Maccabi Healthcare Services experience with a unified testing policy. Nava Siegelmann-Danieli, Barbara Silverman, +3 authors, Avi Porath. less Ecancermedicalscience, 2014 Jan 05; 7. PMID: 24386009 Free PMC article.
Prospective transGEICAM study of the impact of the 21-gene Recurrence Score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer. J Albanell, A González, +17 authors, A Lluch. less Ann Oncol, 2011 Jun 10; 23(3). PMID: 21652577
Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry. Salomon M Stemmer, Mariana Steiner, +13 authors, Noa Ben-Baruch. less NPJ Breast Cancer, 2017 Sep 14; 3. PMID: 28900632 Free PMC article.
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. Fatima Cardoso, Laura J van't Veer, +32 authors, MINDACT Investigators. less N Engl J Med, 2016 Aug 25; 375(8). PMID: 27557300 Highly Cited.
The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy. D B Geffen, S Abu-Ghanem, +6 authors, M Koretz. less Ann Oncol, 2011 Mar 03; 22(11). PMID: 21363879
Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study. Joseph Gligorov, Xavier B Pivot, +11 authors, Francilian Breast Intergroup. less Oncologist, 2015 Jun 27; 20(8). PMID: 26112003 Free PMC article.
The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients. Salomon M Stemmer, Shmuel H Klang, +7 authors, Nicky Lieberman. less Breast Cancer Res Treat, 2013 Jun 27; 140(1). PMID: 23801158 Free PMC article.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology. less J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339 Free PMC article. Highly Cited. Review.
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.
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.
The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use. W Eiermann, M Rezai, +13 authors, J Blohmer. less Ann Oncol, 2012 Nov 09; 24(3). PMID: 23136233 Free PMC article.
The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Josh J Carlson, Joshua A Roth. Breast Cancer Res Treat, 2013 Aug 27; 141(1). PMID: 23974828 Free PMC article. Highly Cited. Systematic Review.
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.
Clinical significance of the 21-gene signature (Oncotype DX) in hormone receptor-positive early stage primary breast cancer in the Japanese population. Masakazu Toi, Hiroji Iwata, +8 authors, Japan Breast Cancer Research Group-Translational Research Group. less Cancer, 2010 Jun 22; 116(13). PMID: 20564629
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. E Senkus, S Kyriakides, +6 authors, ESMO Guidelines Committee. less Ann Oncol, 2015 Sep 01; 26 Suppl 5. PMID: 26314782 Highly Cited.
West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. Oleg Gluz, Ulrike A Nitz, +18 authors, Nadia Harbeck. less J Clin Oncol, 2016 Mar 02; 34(20). PMID: 26926676 Highly Cited.
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.
Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Shmuel H Klang, Ariel Hammerman, +3 authors, John Hornberger. less Value Health, 2010 Apr 24; 13(4). PMID: 20412544
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge. less N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349 Free PMC article. Highly Cited.

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Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry. Salomon M Stemmer, Mariana Steiner, +13 authors, Noa Ben-Baruch. less NPJ Breast Cancer, 2017 Sep 14; 3. PMID: 28900632 Free PMC article.
Validation Study of the American Joint Committee on Cancer Eighth Edition Prognostic Stage Compared With the Anatomic Stage in Breast Cancer. Anna Weiss, Mariana Chavez-MacGregor, +6 authors, Elizabeth A Mittendorf. less JAMA Oncol, 2017 Dec 10; 4(2). PMID: 29222540 Free PMC article.
Practice patterns and outcomes for patients with node-negative hormone receptor-positive breast cancer and intermediate 21-gene Recurrence Scores. Jonathan Chen, Xian Wu, +2 authors, Paul J Christos, Silvia Formenti, Himanshu Nagar. less Breast Cancer Res, 2018 Apr 18; 20(1). PMID: 29661221 Free PMC article.
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge. less N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917 Free PMC article. Highly Cited.
Impact of 21-Gene Breast Cancer Assay on Treatment Decision for Patients with T1-T3, N0-N1, Estrogen Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Breast Cancer: Final Results of the Prospective Multicenter ROXANE Study. Maria Vittoria Dieci, Valentina Guarneri, +16 authors, Veneto Oncology Network. less Oncologist, 2019 Jun 04; 24(11). PMID: 31152079 Free PMC article.
Panoptic View of Prognostic Models for Personalized Breast Cancer Management. Geetanjali Saini, Karuna Mittal, +3 authors, Ritu Aneja. less Cancers (Basel), 2019 Sep 11; 11(9). PMID: 31500225 Free PMC article. Review.
Adjuvant chemotherapy and survival among patients 70 years of age and younger with node-negative breast cancer and the 21-gene recurrence score of 26-30. Seho Park, Yunan Han, +7 authors, Yikyung Park. less Breast Cancer Res, 2019 Oct 18; 21(1). PMID: 31619259 Free PMC article.
Cross-Canada differences in early-stage breast cancer treatment and acute-care use. M Powis, P Groome, +8 authors, M K Krzyzanowska. less Curr Oncol, 2019 Nov 12; 26(5). PMID: 31708656 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.
Gene Expression Profiling Tests for Early-Stage Invasive Breast Cancer: A Health Technology Assessment. Ontario Health (Quality). Ont Health Technol Assess Ser, 2020 Apr 15; 20(10). PMID: 32284770 Free PMC article.
Radiogenomics of magnetic resonance imaging and a new multi-gene classifier for predicting recurrence prognosis in estrogen receptor-positive breast cancer: A preliminary study. Yukiko Tokuda, Masahiro Yanagawa, +3 authors, Noriyuki Tomiyama. less Medicine (Baltimore), 2020 Apr 22; 99(16). PMID: 32311939 Free PMC article.
Should women with early breast cancer under 40 years of age have a routine 21-gene recurrence score testing: A SEER database study. Kai-Hua Liu, Lei Zhang, +4 authors, San-Gang Wu. less Breast, 2020 Jan 10; 49. PMID: 31918322 Free PMC article.
Clinicopathological characteristics, adjuvant chemotherapy decision and disease outcome in patients with breast cancer with a 21-gene recurrence score of 26-30. Jing Yu, Jiayi Wu, +6 authors, Kunwei Shen. less Oncol Lett, 2020 Jul 30; 20(2). PMID: 32724396 Free PMC article.
AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Nina Ditsch, Michael Untch, +42 authors, Achim Wöckel. less Breast Care (Basel), 2019 Sep 29; 14(4). PMID: 31558897 Free PMC article. Review.
The 21-Gene Recurrence Score Assay and Prediction of Chemotherapy Benefit: A Propensity Score-Matched Analysis of the SEER Database. In Sil Choi, Jiwoong Jung, +5 authors, Ki-Tae Hwang. less Cancers (Basel), 2020 Jul 12; 12(7). PMID: 32650374 Free PMC article.
Personalised medicine and the decision to withhold chemotherapy in early breast cancer with intermediate risk of recurrence - a systematic review and meta-analysis. Susanna M Wallerstedt, Astrid Nilsson Ek, +3 authors, Barbro Linderholm. less Eur J Clin Pharmacol, 2020 Jun 07; 76(9). PMID: 32504183 Free PMC article. Review.
The Distribution and Outcomes of the 21-Gene Recurrence Score in T1-T2N0 Estrogen Receptor-Positive Breast Cancer With Different Histologic Subtypes. Jun Wang, Zhen-Yu He, +3 authors, San-Gang Wu. less Front Genet, 2019 Jan 09; 9. PMID: 30619463 Free PMC article.
Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer. Lizhe Zhu, Nan Ma, +5 authors, Yu Ren. less Oncol Lett, 2019 Jun 13; 17(6). PMID: 31186766 Free PMC article.
Adjuvant radiation therapy alone is associated with improved overall survival compared to hormonal therapy alone in older women with estrogen receptor positive early stage breast cancer. Sachin R Jhawar, Naomi Alpert, +8 authors, Nisha Ohri. less Cancer Med, 2020 Sep 18; 9(22). PMID: 32942344 Free PMC article.
Chemotherapy and 21-gene recurrence score testing for older breast cancer patients: A competing-risks analysis. Ping Zhou, Wen-Wen Zhang, +4 authors, San-Gang Wu. less Breast, 2020 Dec 06; 54. PMID: 33278648 Free PMC article.

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