Journal Article
. 2018 Nov;125(2).
doi: 10.1002/cncr.31818.

Community clinical practice patterns and mortality in patients with intermediate oncotype DX recurrence scores: Who benefits from chemotherapy?

Abiola F Ibraheem 1 David J Press 2 Olufunmilayo I Olopade 1 Dezheng Huo 1 
Affiliations
  • PMID: 30387876
  •     34 References
  •     9 citations

Abstract

Background: The Oncotype DX recurrence score (RS) is used as a tool for making decisions about chemotherapy for patients who have hormone receptor (estrogen receptor or progesterone receptor)-positive, HER2-negative breast cancer. There is no benefit from chemotherapy among patients aged ≥50 years who have lymph node-negative disease and an RS from 11 to 25, but the benefit of chemotherapy in the lymph node-positive group remains unknown.

Methods: On the basis of data from the National Cancer Data Base between 2010 and 2014, a nationwide, retrospective cohort study included 73,185 women who had stage I through IIIA breast cancer and an RS between 11 and 30.

Results: Receipt of chemotherapy was associated with a reduced risk of death among patients who had lymph node-positive breast cancer (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.45-0.74; P < .001) after adjusting for other prognostic factors in a multivariable Cox model. The 5-year survival gain ranged from 1.3% (RS 11-17 subgroup), to 3.3% (RS 18-25 subgroup), and to 6.7% (RS 26-30 subgroup). Among patients who had lymph node-negative disease, chemotherapy was associated with a reduced risk of death for those with an RS from 25 to 30 (HR, 0.68; 95% CI, 0.48-0.96; P = .03; 5-year survival gain, 1.8%), but there was no benefit from chemotherapy for patients who had an RS from 11 to 17 (HR, 0.97; 95% CI, 0.61-1.55; P = .90), and there was a marginally significant benefit for women who had an RS from 18 to 25 (HR, 0.79; 95% CI, 0.62-1.00; P = .05). Similar results were observed using propensity score-matching method.

Conclusions: The benefit of chemotherapy for patients with breast cancer who have an intermediate RS is driven in a nonlinear fashion by RS: the higher the RS, the larger the absolute benefit. Findings from this study underscore the utility of real-world data to inform joint decision making in practice.

Keywords: Oncotype DX; breast cancer; lymph node-negative; lymph node-positive; recurrence score.

Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention.
V B Pai, M C Nahata.
Drug Saf, 2000 May 02; 22(4). PMID: 10789823
Highly Cited. Review.
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.
Breast Cancer Res, 2006 Jun 02; 8(3). PMID: 16737553    Free PMC article.
Highly Cited.
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.
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.
Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.
Armando E Giuliano, James L Connolly, +6 authors, Gabriel N Hortobagyi.
CA Cancer J Clin, 2017 Mar 16; 67(4). PMID: 28294295
Highly Cited.
Utilization and impact of 21-gene recurrence score assay for breast cancer in clinical practice across the United States: lessons learned from the 2010 to 2012 National Cancer Data Base analysis.
Amila Orucevic, Robert E Heidel, John L Bell.
Breast Cancer Res Treat, 2016 May 22; 157(3). PMID: 27206678    Free PMC article.
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.
J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838    Free PMC article.
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.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Development of the 21-gene assay and its application in clinical practice and clinical trials.
Joseph A Sparano, Soonmyung Paik.
J Clin Oncol, 2008 Feb 09; 26(5). PMID: 18258979
Highly Cited. Review.
Prognostic significance of Nottingham histologic grade in invasive breast carcinoma.
Emad A Rakha, Maysa E El-Sayed, +5 authors, Ian O Ellis.
J Clin Oncol, 2008 May 21; 26(19). PMID: 18490649
Highly Cited.
Using the NCDB for cancer care improvement: an introduction to available quality assessment tools.
Mehul V Raval, Karl Y Bilimoria, +2 authors, Clifford Y Ko.
J Surg Oncol, 2009 May 26; 99(8). PMID: 19466738
Review.
Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer.
B Fisher, J Dignam, +10 authors, R G Margolese.
J Natl Cancer Inst, 1997 Dec 09; 89(22). PMID: 9390536
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.
21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile.
Jagar Jasem, Arya Amini, +4 authors, Peter Kabos.
J Clin Oncol, 2016 Mar 24; 34(17). PMID: 27001563    Free PMC article.
Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies.
Stephen K Chia, Caroline H Speers, +2 authors, Ivo A Olivotto.
J Clin Oncol, 2004 May 01; 22(9). PMID: 15117985
Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.
Peter C Austin.
Stat Med, 2009 Sep 17; 28(25). PMID: 19757444    Free PMC article.
Highly Cited.
Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials.
Bernard Fisher, Jong-Hyeon Jeong, +5 authors, National Surgical Adjuvant Breast and Bowel Project randomised clinical trials.
Lancet, 2004 Sep 08; 364(9437). PMID: 15351193
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.
Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
R A Deyo, D C Cherkin, M A Ciol.
J Clin Epidemiol, 1992 Jun 01; 45(6). PMID: 1607900
Highly Cited.
Decline in the use of anthracyclines for breast cancer.
Sharon H Giordano, Yu-Li Lin, +2 authors, James S Goodwin.
J Clin Oncol, 2012 May 23; 30(18). PMID: 22614988    Free PMC article.
Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes.
Scott D Ramsey, William E Barlow, +6 authors, Gabriel N Hortobagyi.
Contemp Clin Trials, 2012 Sep 25; 34(1). PMID: 23000081    Free PMC article.
Review.
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.
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.
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
Antonio C Wolff, M Elizabeth H Hammond, +19 authors, College of American Pathologists.
Arch Pathol Lab Med, 2013 Oct 09; 138(2). PMID: 24099077    Free PMC article.
Highly Cited.
The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
Karl Y Bilimoria, Andrew K Stewart, David P Winchester, Clifford Y Ko.
Ann Surg Oncol, 2008 Jan 10; 15(3). PMID: 18183467    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.
Comparison of commission on cancer-approved and -nonapproved hospitals in the United States: implications for studies that use the National Cancer Data Base.
Karl Y Bilimoria, David J Bentrem, +2 authors, Clifford Y Ko.
J Clin Oncol, 2009 Jul 29; 27(25). PMID: 19636004
Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines.
D Bovelli, G Plataniotis, F Roila, ESMO Guidelines Working Group.
Ann Oncol, 2010 Jun 29; 21 Suppl 5. PMID: 20555097
Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment.
Maria Volkova, Raymond Russell.
Curr Cardiol Rev, 2012 Jul 05; 7(4). PMID: 22758622    Free PMC article.
Highly Cited. Review.
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.
N Engl J Med, 1989 Feb 23; 320(8). PMID: 2644532
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.
Lancet, 2011 Aug 02; 378(9793). PMID: 21802721    Free PMC article.
Highly Cited.
Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.
Megan C Roberts, Dave P Miller, Steven Shak, Valentina I Petkov.
Breast Cancer Res Treat, 2017 Mar 01; 163(2). PMID: 28243896
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.
Cancer, 2010 Jun 22; 116(13). PMID: 20564629
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.
Breast Cancer Res, 2019 Oct 18; 21(1). PMID: 31619259    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.
NPJ Breast Cancer, 2019 Nov 16; 5. PMID: 31728408    Free PMC article.
Lymph node involvement: Positive about the role of the recurrence score in estrogen-driven breast cancer?
Kevin Kalinsky, Ruth M O'Regan.
Cancer, 2018 Nov 06; 125(2). PMID: 30387877    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.
Nodal positivity decreases with age in women with early-stage, hormone receptor-positive breast cancer.
Stephanie M Downs-Canner, Charles E Gaber, +4 authors, David W Ollila.
Cancer, 2019 Dec 21; 126(6). PMID: 31860136    Free PMC article.
Sex Disparity Observed for Oncotype DX Breast Recurrence Score in Predicting Mortality Among Patients with Early Stage ER-Positive Breast Cancer.
Fei Wang, Sonya Reid, +6 authors, Xiao-Ou Shu.
Clin Cancer Res, 2019 Nov 22; 26(1). PMID: 31748278    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.
Oncol Lett, 2020 Jul 30; 20(2). PMID: 32724396    Free PMC article.
Propensity score analysis of the prognostic value of genomic assays for breast cancer in diverse populations using the National Cancer Data Base.
Abiola Ibraheem, Olufunmilayo I Olopade, Dezheng Huo.
Cancer, 2020 Jun 11; 126(17). PMID: 32521056    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.
Eur J Clin Pharmacol, 2020 Jun 07; 76(9). PMID: 32504183    Free PMC article.
Review.