Journal Article
. 2019 Dec;38(7).
doi: 10.1200/JCO.19.01959.

Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer

Philip D Poorvu 1 Shari I Gelber 1 Shoshana M Rosenberg 1 Kathryn J Ruddy 2 Rulla M Tamimi 3 Laura C Collins 4 Jeffrey Peppercorn 5 Lidia Schapira 6 Virginia F Borges 7 Steven E Come 4 Ellen Warner 8 Debbie M Jakubowski 9 Christy Russell 9 Eric P Winer 1 Ann H Partridge 1 
Affiliations
  • PMID: 31809240
  •     37 References
  •     3 citations

Abstract

Purpose: The 21-gene recurrence score (RS) assay is prognostic among women with early-stage estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer and is used to inform recommendations for chemotherapy. Women ≤ 40 years of age represent a minority of patients studied using gene expression profiles.

Methods: The Young Women's Breast Cancer Study is a prospective cohort of women diagnosed with breast cancer at age ≤ 40 years and enrolled patients between 2006 and 2016 (N = 1,302). We identified patients with stage I-III ER+/HER2- breast cancer. The RS assay was performed on banked specimens for patients who had not been tested clinically. Distant recurrence-free survival (DRFS) was assessed by TAILORx and traditional RS risk groups among patients with axillary node-negative (N0) and limited node-positive (N1) breast cancer.

Results: Among eligible women (N = 577), 189 (33%) had undergone RS testing, and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6.0 years. Median age at diagnosis was 37.2 years; 300 of 509 patients (59%) had N0 breast cancer, of whom 195 (65%) had an RS of 11-25 and fewer than half (86 of 195; 44%) received chemotherapy. Six-year DRFS rates were 94.4% and 92.3% (RS < 11), 96.9% and 85.2% (RS 11-25), and 85.1% and 71.3% (RS ≥ 26) among women with N0 and N1 disease, respectively.

Conclusion: The RS assay is prognostic among young women with node-negative and limited node-positive breast cancer, representing a valuable tool for risk stratification. Disease outcomes with a median follow-up of 6 years among young women with N0 disease and an RS of 0-25, a minority of whom received chemotherapy, and node-positive disease with an RS < 11 were very good, whereas those with N0 disease and an RS ≥ 26 or N1 disease with an RS ≥ 11 experienced substantial risk of early distant recurrence.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Relationship between age at diagnosis and outcome of premenopausal breast cancer: age less than 35 years is a reasonable cut-off for defining young age-onset breast cancer.
Wonshik Han, So Young Kang, Korean Breast Cancer Society.
Breast Cancer Res Treat, 2009 Apr 08; 119(1). PMID: 19350387
Adjuvant ovarian suppression in premenopausal breast cancer.
Prudence A Francis, Meredith M Regan, +28 authors, International Breast Cancer Study Group.
N Engl J Med, 2014 Dec 17; 372(5). PMID: 25495490    Free PMC article.
Highly Cited.
Temporal trends in breast cancer survival in Sweden: significant improvement in 20 years.
H O Adami, B Malker, +2 authors, L Ries.
J Natl Cancer Inst, 1986 Apr 01; 76(4). PMID: 3457203
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update-Integration of Results From TAILORx.
Fabrice Andre, Nofisat Ismaila, +10 authors, Vered Stearns.
J Clin Oncol, 2019 Jun 01; 37(22). PMID: 31150316
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
Highly Cited.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Distribution of 21-Gene Recurrence Scores Among Breast Cancer Histologic Subtypes.
Scott Kizy, Jing Li Huang, +5 authors, Jane Yuet Ching Hui.
Arch Pathol Lab Med, 2018 Mar 13; 142(6). PMID: 29528718
Purposeful selection of variables in logistic regression.
Zoran Bursac, C Heath Gauss, David Keith Williams, David W Hosmer.
Source Code Biol Med, 2008 Dec 18; 3. PMID: 19087314    Free PMC article.
Highly Cited.
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.
N Engl J Med, 2019 Jun 04; 380(25). PMID: 31157962    Free PMC article.
Highly Cited.
Recent Trends in Chemotherapy Use and Oncologists' Treatment Recommendations for Early-Stage Breast Cancer.
Allison W Kurian, Irina Bondarenko, +7 authors, Steven J Katz.
J Natl Cancer Inst, 2017 Dec 14; 110(5). PMID: 29237009    Free PMC article.
West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer.
Ulrike Nitz, Oleg Gluz, +18 authors, West German Study Group PlanB Investigators.
J Clin Oncol, 2019 Feb 21; 37(10). PMID: 30785826
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.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.
Prudence A Francis, Olivia Pagani, +34 authors, SOFT and TEXT Investigators and the International Breast Cancer Study Group.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29863451    Free PMC article.
Highly Cited.
Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease.
Jennifer L Gnerlich, Anjali D Deshpande, +3 authors, Julie A Margenthaler.
J Am Coll Surg, 2009 Mar 26; 208(3). PMID: 19317994    Free PMC article.
Highly Cited.
Use and Costs for Tumor Gene Expression Profiling Panels in the Management of Breast Cancer From 2006 to 2012: Implications for Genomic Test Adoption Among Private Payers.
Megan C Roberts, Stacie B Dusetzina.
J Oncol Pract, 2015 Jun 25; 11(4). PMID: 26105668
Adoption of gene expression profile testing and association with use of chemotherapy among women with breast cancer.
Michael J Hassett, Samuel M Silver, +12 authors, Jane C Weeks.
J Clin Oncol, 2012 May 16; 30(18). PMID: 22585699    Free PMC article.
Breast cancer in young women: poor survival despite intensive treatment.
Hanna Fredholm, Sonja Eaker, +3 authors, Henrik Lindman.
PLoS One, 2009 Nov 13; 4(11). PMID: 19907646    Free PMC article.
Highly Cited.
Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival.
Ann H Partridge, Melissa E Hughes, +9 authors, Rulla M Tamimi.
J Clin Oncol, 2016 Aug 03; 34(27). PMID: 27480155
Highly Cited.
Treatment Efficacy, Adherence, and Quality of Life Among Women Younger Than 35 Years in the International Breast Cancer Study Group TEXT and SOFT Adjuvant Endocrine Therapy Trials.
Poornima Saha, Meredith M Regan, +25 authors, International Breast Cancer Study Group.
J Clin Oncol, 2017 Jun 28; 35(27). PMID: 28654365    Free PMC article.
Occurrence of breast cancer subtypes in adolescent and young adult women.
Theresa H M Keegan, Mindy C DeRouen, +2 authors, Christina A Clarke.
Breast Cancer Res, 2012 Mar 29; 14(2). PMID: 22452927    Free PMC article.
Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort.
Anna L V Johansson, Cassia B Trewin, +3 authors, Giske Ursin.
Int J Cancer, 2018 Oct 28; 144(6). PMID: 30367449
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.
J Clin Oncol, 2016 Mar 02; 34(20). PMID: 26926676
Highly Cited.
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.
N Engl J Med, 2016 Aug 25; 375(8). PMID: 27557300
Highly Cited.
Prospective observational study of breast cancer treatment outcomes for UK women aged 18-40 years at diagnosis: the POSH study.
Ellen Copson, Bryony Eccles, +11 authors, POSH Study Steering Group.
J Natl Cancer Inst, 2013 Jun 01; 105(13). PMID: 23723422
Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.
Olivia Pagani, Meredith M Regan, +32 authors, International Breast Cancer Study Group.
N Engl J Med, 2014 Jun 03; 371(2). PMID: 24881463    Free PMC article.
Highly Cited.
TAILORing Adjuvant Systemic Therapy for Breast Cancer.
Vered Stearns.
N Engl J Med, 2018 Jul 12; 379(2). PMID: 29996081
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.
J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256
Highly Cited.
Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study.
Jeanne A Petrek, Michelle J Naughton, +4 authors, Paniti Sukumvanich.
J Clin Oncol, 2006 Feb 16; 24(7). PMID: 16476708
Incidence and time course of bleeding after long-term amenorrhea after breast cancer treatment: a prospective study.
Paniti Sukumvanich, L Doug Case, +5 authors, Michelle J Naughton.
Cancer, 2010 Jun 22; 116(13). PMID: 20564648
Incidence and Survival Among Young Women With Stage I-III Breast Cancer: SEER 2000-2015.
Alexandra Thomas, Anthony Rhoads, +7 authors, Paul A Romitti.
JNCI Cancer Spectr, 2019 Aug 09; 3(3). PMID: 31392297    Free PMC article.
ESO-ESMO 3rd international consensus guidelines for breast cancer in young women (BCY3).
Shani Paluch-Shimon, Olivia Pagani, +15 authors, Fatima Cardoso.
Breast, 2017 Aug 20; 35. PMID: 28822332
Highly Cited.
Young age: an independent risk factor for disease-free survival in women with operable breast cancer.
Wonshik Han, Seok Won Kim, +6 authors, Dong-Young Noh.
BMC Cancer, 2004 Nov 18; 4. PMID: 15546499    Free PMC article.
Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling.
Hatem A Azim, Stefan Michiels, +7 authors, Sherene Loi.
Clin Cancer Res, 2012 Jan 21; 18(5). PMID: 22261811
Highly Cited.
Being 40 or younger is an independent risk factor for relapse in operable breast cancer patients: the Saudi Arabia experience.
Naser Elkum, Said Dermime, +7 authors, Taher Al-Tweigeri.
BMC Cancer, 2007 Dec 07; 7. PMID: 18053234    Free PMC article.
Current State of the Art in the Adjuvant Systemic Treatment of Premenopausal Patients With Early Breast Cancer.
Francesca Parisi, Maria Grazia Razeti, +7 authors, Matteo Lambertini.
Clin Med Insights Oncol, 2020 Jul 11; 14. PMID: 32647477    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.
NPJ Breast Cancer, 2020 Oct 17; 6. PMID: 33062888    Free PMC article.
Review.
Oncotype DX Breast Recurrence Score Distribution and Chemotherapy Benefit Among Women of Different Age Groups With HR-Positive, HER2-Negative, Node-Negative Breast Cancer in the SEER Database.
Ran Cheng, Xiangyi Kong, +2 authors, Jing Wang.
Front Oncol, 2020 Nov 17; 10. PMID: 33194568    Free PMC article.