NCCN Guidelines® Insights: Breast Cancer, Version 4.2021

Featured Updates to the NCCN Guidelines

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  • 1 Robert H. Lurie Comprehensive Cancer Center of Northwestern University;
  • | 2 Yale Cancer Center/Smilow Cancer Hospital;
  • | 3 Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;
  • | 4 Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;
  • | 5 The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;
  • | 6 Stanford Cancer Institute;
  • | 7 UC San Diego Moores Cancer Center;
  • | 8 Dana-Farber/Brigham and Women’s Cancer Center;
  • | 9 Memorial Sloan Kettering Cancer Center;
  • | 10 University of Colorado Cancer Center;
  • | 11 The University of Texas MD Anderson Cancer Center;
  • | 12 Mayo Clinic Cancer Center;
  • | 13 Fox Chase Cancer Center;
  • | 14 UCLA Jonsson Comprehensive Cancer Center;
  • | 15 Massachusetts General Hospital Cancer Center;
  • | 16 Abramson Cancer Center at the University of Pennsylvania;
  • | 17 Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance;
  • | 18 Fred & Pamela Buffet Cancer Center;
  • | 19 UT Southwestern Simmons Comprehensive Cancer Center;
  • | 20 Vanderbilt-Ingram Cancer Center;
  • | 21 City of Hope National Medical Center;
  • | 22 University of Wisconsin Carbone Cancer Center;
  • | 23 University of Michigan Rogel Cancer Center;
  • | 24 UCSF Helen Diller Family Comprehensive Cancer Center;
  • | 25 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;
  • | 26 Research Advocacy Network;
  • | 27 Moffitt Cancer Center;
  • | 28 O'Neal Comprehensive Cancer Center at UAB;
  • | 29 Huntsman Cancer Institute at the University of Utah;
  • | 30 Roswell Park Comprehensive Cancer Center; and
  • | 31 National Comprehensive Cancer Network.
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The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.

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    Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published online February 4, 2021]. CA Cancer J Clin,

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    Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 2006;295:16581667.

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    Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:28172826.

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    Dowsett M, Cuzick J, Wale C, et al. 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. J Clin Oncol 2010;28:18291834.

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    Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 2010;28:16771683.

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  • 7.

    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;11:5565.

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    Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:37263734.

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  • 9.

    Tang G, Shak S, Paik S, et al. Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20. Breast Cancer Res Treat 2011;127:133142.

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    Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379:111121.

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  • 11.

    Gluz O, Nitz UA, Christgen M, et al. 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. J Clin Oncol 2016;34:23412349.

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  • 12.

    Cardoso F, van’t Veer LJ, Poncet C, et al. MINDACT: long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. Presented at the ASCO Virtual Scientific Program 2020; May 29–31, 2020. Abstract 506.

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  • 13.

    Piccart M, van’t Veer LJ, Poncet C, et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol 2021;22:476488.

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  • 14.

    Kalinsky KB, Barlow WE, Meric-Bernstam F, et al. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/− chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). Presented at the 2020 CTRC-AACR San Antonio Breast Cancer Symposium; December 8–11, 2020; San Antonio, Texas. Abstract GS3-00.

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    Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, et al. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst 2018;110:110.

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    Noordhoek I, Treuner K, Putter H, et al. Breast cancer index predicts extended endocrine benefit to individualize selection of patients with HR+ early-stage breast cancer for 10 years of endocrine therapy. Clin Cancer Res 2021;27:311319.

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    Sgroi DC, Sestak I, Cuzick J, et al. 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. Lancet Oncol 2013;14:10671076.

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  • 18.

    Bartlett JMS, Sgroi DC, Treuner K, et al. Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. Ann Oncol 2019;30:17761783.

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  • 19.

    Sparano J, Gray RJ, Wood WC, et al. TAILORx: phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score [abstract]. J Clin Oncol 2018;36(Suppl):Abstract LBA1.

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  • 20.

    Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med 2018;379:122137.

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