Application of 21-Gene test in adjuvant radiotherapy for early breast cancer

doi:10.16139/j.1007-9610.2024.03.15

Abstract

Abstract:

Breast cancer is the most common malignant tumor in women. With the development of genomics technology and medical frontier technology, the systemic treatment of breast cancer has gradually entered the era of personalized medicine. However, the decision-making of adjuvant radiotherapy for breast cancer still mainly relies on traditional clinicopathological factors, and there is a lack of scientific and reliable tools to guide precise radiotherapy in different populations. Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer is the most common molecular subtype of breast cancer. The 21-Gene recurrence score (RS) test (Oncotype Dx™, Genomic Health, Redwood City, CA) is a commercially available genomic test for breast cancer. In this article, we reviewed the current research evidence on the use of 21-Gene RS test for radiotherapy decision-making in HR-positive HER2-negative early breast cancer. Current clinical studies support the predictive value of 21-Gene RS test for adjuvant radiotherapy, and several large-scale prospective clinical studies in this area are underway.

Key words: Breast cancer, Radiotherapy, 21-Gene recurrence score

CLC Number:

R737.9
R815

TANG Xiaolu, HUA Xin, CAO Lu, CHEN Jiayi. Application of 21-Gene test in adjuvant radiotherapy for early breast cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(03): 270-276.

Figures/Tables 1

References 56

[1]	HARVEY J M, CLARK G M, OSBORNE C K, et al. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer[J]. J Clin Oncol, 2023, 41(7):1331-1338. doi: 10.1200/JCO.22.02500 pmid: 36827742
[2]	ARISTEI C, PERRUCCI E, ALÌ E, et al. Personalization in modern radiation oncology: methods, results and pitfalls.Personalized interventions and breast cancer[J]. Front Oncol, 2021, 11:616042.
[3]	KRUG D, BAUMANN R, BUDACH W, et al. Commercially available gene expression assays as predictive tools for adjuvant radiotherapy? A critical review[J]. Breast Care (Basel), 2020, 15(2):118-126.
[4]	WU S G, ZHANG W W, WANG J, et al. Effect of 21-Gene recurrence score in decision-making for surgery in early stage breast cancer[J]. Onco Targets Ther, 2019, 12:2071-2078.
[5]	BUSHARA O, HANSEN N M. Genetic considerations in the locoregional management of breast cancer: a review of current evidence[J]. Curr Breast Cancer Rep, 2023, 15:48-57.
[6]	MAMOUNAS E P, MITCHELL M P, WOODWARD W A. Molecular predictive and prognostic markers in locoregional management[J]. J Clin Oncol, 2020, 38(20):2310-2320. doi: 10.1200/JCO.19.02905 pmid: 32442060
[7]	TURASHVILI G, WEN H Y. Multigene testing in breast cancer: what have we learned from the 21-Gene recurrence score assay?[J]. Breast J, 2020, 26(6):1199-1207.
[8]	National Comprehensive Cancer Network^®. NCCN Guidelines^®:breast cancer,version 5.2023[G/OL]. [2023-02-08]. https://www.nccn.org/login?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
[9]	ANDRE F, ISMAILA N, ALLISON K H, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update[J]. J Clin Oncol, 2022, 40(16):1816-1837.
[10]	Guidelines of Chinese Society of Clinical Oncology CSCO 2023: breast cancer[G/OL]. [2023-02-08]. https://www.csco.org.cn/cn/index.aspx.
[11]	China Anti-Cancer Association Committee Of Breast Cancer Society CACA-CBCS. Guidelines and norms of breast cancer(2021)[J]. Chin Oncol, 2021, 31(10):954-1040.
[12]	PAIK S, SHAK S, TANG G, et al. A multigene assay to predict recurrence of tamoxifen-treated,node-negative breast cancer[J]. N Engl J Med, 2004, 351(27):2817-2826.
[13]	SPARANO J A, PAIK S. Development of the 21-Gene assay and its application in clinical practice and clinical trials[J]. J Clin Oncol, 2008, 26(5):721-728. doi: 10.1200/JCO.2007.15.1068 pmid: 18258979
[14]	SPARANO J A, GRAY R J, RAVDIN P M, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer[J]. N Engl J Med, 2019, 380(25):2395-2405.
[15]	ANDRE F, ISMAILA N, HENRY N L, et al. 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[J]. J Clin Oncol, 2019, 37(22):1956-1964. doi: 10.1200/JCO.19.00945 pmid: 31150316
[16]	CARDOSO F, KYRIAKIDES S, OHNO S, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2019, 30(8):1194-1220.
[17]	SJÖSTRÖM M, CHANG S L, FISHBANE N, et al. Clinicogenomic radiotherapy classifier predicting the need for intensified locoregional treatment after breast-conserving surgery for early-stage breast cancer[J]. J Clin Oncol, 2019, 37(35):3340-3349. doi: 10.1200/JCO.19.00761 pmid: 31618132
[18]	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]. J Clin Oncol, 2006, 24(23):3726-3734. doi: 10.1200/JCO.2005.04.7985 pmid: 16720680
[19]	ALBAIN K S, BARLOW W E, 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[J]. Lancet Oncol, 2010, 11(1):55-65. doi: 10.1016/S1470-2045(09)70314-6 pmid: 20005174
[20]	GEYER C E, TANG G, MAMOUNAS E P, et al. 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer[J]. NPJ breast cancer, 2018, 4:37. doi: 10.1038/s41523-018-0090-6 pmid: 30456299
[21]	FALCO M, MASOJĆ B, KRAM A. Locoregional relapse is a strong prognostic indicator of distant metastatic progression in breast cancer patients after negative sentinel lymph node biopsy[J]. Breast J, 2020, 26:2364-2370.
[22]	ZHAO X, TANG Y, WANG S, et al. Locoregional recurrence patterns in women with breast cancer who have not undergone post-mastectomy radiotherapy[J]. Radiat Oncol, 2020, 15(1):212. doi: 10.1186/s13014-020-01637-w pmid: 32887640
[23]	DAVEY M G, CLEERE E F, O'DONNELL J P, et al. Value of the 21-Gene expression assay in predicting locoregional recurrence rates in estrogen receptor-positive breast cancer: a systematic review and network meta-analysis[J]. Breast Cancer Res Treat, 2022, 193(3):535-544.
[24]	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]. J Clin Oncol, 2010, 28(11):1829-1834. doi: 10.1200/JCO.2009.24.4798 pmid: 20212256
[25]	MAMOUNAS E P, LIU Q, PAIK S, et al. 21-Gene recurrence score and locoregional recurrence in node-positive/ER-positive breast cancer treated with chemo-endocrine therapy[J]. J Natl Cancer Inst, 2017, 109(4):djw259.
[26]	YORDANOVA M, HASSAN S. The role of the 21-Gene Recurrence Score(®) assay in hormone receptor-positive, node-positive breast cancer: the Canadian experience[J]. Curr Oncol, 2022, 29(3):2008-2020.
[27]	VARGA Z, SINN P, SEIDMAN A D. Summary of head-to-head comparisons of patient risk classifications by the 21-Gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer[J]. Int J Cancer, 2019, 145(4):882-893. doi: 10.1002/ijc.32139 pmid: 30653259
[28]	CAPUTO R, CIANNIELLO D, GIORDANO A, et al. Gene expression assay in the management of early breast cancer[J]. Curr Med Chem, 2020, 27(17):2826-2839. doi: 10.2174/0929867326666191205163329 pmid: 31804159
[29]	GIORGI ROSSI P, LEBEAU A, CANELO-AYBAR C, et al. Recommendations from the European commission initiative on breast cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer,hormone receptor positive, HER-2 negative[J]. Br J Cancer, 2021, 124(9):1503-1512.
[30]	AUGUSTOVSKI F, SOTO N, CAPORALE J, et al. Decision-making impact on adjuvant chemotherapy allocation in early node-negative breast cancer with a 21-Gene assay:systematic review and meta-analysis[J]. Breast Cancer Res Treat, 2015, 152(3):611-625.
[31]	HARNAN S, TAPPENDEN P, COOPER K, et al. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis[J]. Health Technol Assess, 2019, 23(30):1-328. doi: 10.3310/hta23300 pmid: 31264581
[32]	WOODWARD W A, BARLOW W E, JAGSI R, et al. Association between 21-gene assay recurrence score and locoregional recurrence rates in patients with node-positive breast cancer[J]. JAMA oncol, 2020, 6(4):505-511. doi: 10.1001/jamaoncol.2019.5559 pmid: 31917424
[33]	CHEVLI N, HAQUE W, TRAN K T, et al. Role of 21-Gene recurrence score in predicting prognostic benefit of radiation therapy after breast-conserving surgery for T1N0 breast cancer[J]. Pract Radiat Oncol, 2023, 13(3):e230-e238.
[34]	WU S G, ZHANG W W, WANG J, et al. 21-Gene recurrence score assay and outcomes of adjuvant radiotherapy in elderly women with early-stage breast cancer after breast-conserving surgery[J]. Front Oncol, 2019, 9:1.
[35]	DONG Y, ZHANG W W, WANG J, et al. The 21-Gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer[J]. Future Oncol, 2019, 15(14):1629-1639. doi: 10.2217/fon-2018-0967 pmid: 30864836
[36]	JAYASEKERA J, SCHECHTER C B, SPARANO J A, et al. Effects of radiotherapy in early-stage, low-recurrence risk, hormone-sensitive breast cancer[J]. J Natl Cancer Inst, 2018, 110(12):1370-1379. doi: 10.1093/jnci/djy128 pmid: 30239794
[37]	GOODMAN C R, SEAGLE B L, KOCHERGINSKY M, et al. 21-Gene recurrence score assay predicts benefit of post-mastectomy radiotherapy in T1-2 N1 breast cancer[J]. Clin Cancer Res, 2018, 24(16):3878-3887. doi: 10.1158/1078-0432.CCR-17-3169 pmid: 29685878
[38]	WU S G, HE Z Y, LI Q, et al. Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy[J]. Breast, 2012, 21(5):657-661.
[39]	HUGHES K S, SCHNAPER L A, BELLON J R, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343[J]. J Clin Oncol, 2013, 31(19):2382-2387. doi: 10.1200/JCO.2012.45.2615 pmid: 23690420
[40]	BUSZEK S M, LIN H Y, BEDROSIAN I, et al. Lumpectomy plus hormone or radiation therapy alone for women aged 70 years or older with hormone receptor-positive early stage breast cancer in the modern era: an analysis of the national cancer database[J]. Int J Radiat Oncol Biol Phys, 2019, 105(4):795-802.
[41]	CHEVLI N, HAQUE W, TRAN K T, et al. 21-Gene recurrence score predictive for prognostic benefit of radiotherapy in patients age ≥ 70 with T1N0 ER/PR⁺ HER2^- breast cancer treated with breast conserving surgery and endocrine therapy[J]. Radiother Oncol, 2022, 174:37-43.
[42]	RECHT A, COMEN E A, FINE R E, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update[J]. J Clin Oncol, 2016, 34(36):4431-4442. doi: 10.1200/JCO.2016.69.1188 pmid: 27646947
[43]	KIMURA Y, SASADA S, GODA N, et al. Therapeutic value of postmastectomy radiation therapy for T1-2 breast cancer with 1-3 positive lymph nodes[J]. J Radiat Oncol, 2019, 8:323-328.
[44]	LUO C, ZHONG X, DENG L, et al. Nomogram predicting locoregional recurrence to assist decision-making of postmastectomy radiation therapy in patients with T1-2N1 breast cancer[J]. Int J Radiat Oncol Biol Phys, 2019, 103(4):905-912.
[45]	LUO C, ZHONG X, FAN Y, et al. The effect of postmastectomy radiation therapy on high-risk patients with T1-2N0 breast cancer[J]. Breast, 2021, 60:1-5. doi: 10.1016/j.breast.2021.08.006 pmid: 34455226
[46]	YAMADA A, HAYASHI N, KUMAMARU H, et al. Prognostic impact of postoperative radiotherapy in patients with breast cancer and with pT1-2 and 1-3 lymph node metastases: a retrospective cohort study based on the Japanese Breast Cancer Registry[J]. Eur J Cancer, 2022, 172:31-40. doi: 10.1016/j.ejca.2022.05.017 pmid: 35752154
[47]	KYNDI M, OVERGAARD M, NIELSEN H M, et al. High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c[J]. Radiother Oncol, 2009, 90(1):74-79.
[48]	WHELAN T J, OLIVOTTO I A, PARULEKAR W R, et al. Regional nodal irradiation in early-stage breast cancer[J]. N Engl J Med, 2015, 373(4):307-316.
[49]	HE L, LV Y, SONG Y, et al. The prognosis comparison of different molecular subtypes of breast tumors after radiotherapy and the intrinsic reasons for their distinct radiosensitivity[J]. Cancer Manag Res, 2019, 11:5765-5775. doi: 10.2147/CMAR.S213663 pmid: 31303789
[50]	MEEHAN J, GRAY M, MARTÍNEZ-PÉREZ C, et al. Precision medicine and the role of biomarkers of radiotherapy response in breast cancer[J]. Front Oncol, 2020, 10:628. doi: 10.3389/fonc.2020.00628 pmid: 32391281
[51]	POORTMANS P M, WELTENS C, FORTPIED C, et al. Internal mammary and medial supraclavicular lymph node chain irradiation in stage Ⅰ-Ⅲ breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial[J]. Lancet Oncol, 2020, 21(12):1602-1610.
[52]	ZHANG W W, TONG Q, SUN J Y, et al. 21-Gene recurrence score assay could not predict benefit of post-mastectomy radiotherapy in T1-2 N1mic ER-positive HER2-negative breast cancer[J]. Front Oncol, 2019, 9:270.
[53]	The IDEA Study (Individualized Decisions for Endocrine Therapy Alone)[G/OL]. [2023-02-08]. https://www.clinicaltrials.gov/study/NCT02400190.
[54]	PARULEKAR W R, BERRANG T, KONG I, et al. Cctg MA.39 tailor RT: a randomized trial of regional radiotherapy in biomarker low-risk node-positive breast cancer (NCT03488693)[J]. J Clin Oncol, 2019, 37(15 suppl):TPS602-TPS602.
[55]	e-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)[G/OL]. [2023-02-08]. https://www.clinicaltrials.gov/study/NCT04852887.
[56]	PRAT A, PARKER J S, FAN C, et al. Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen[J]. Ann Oncol, 2012, 23(11):2866-2873. doi: S0923-7534(19)37503-9 pmid: 32018740

Item	IDEA	TAILOR RT	DEBRA
Study type	Interventional	Interventional	Interventional
Estimated enrollment	202	2 140	1 670
Allocation	N/A	Randomized	Randomized
Intercention model	Single group assignment	Parallel assignment	Parallel assignment
Masking	Open label	Open label	Open label
Ages eligible for study(Years)	50-69	≥35	50-70
TNM stage	pT1N0M0	pT1-2N1 or pT3N0	pT1N0
Surgery	BCS^a)	BCS or Mastectomy	Lumpectomy
Recurrence score	≤18	≤25	≤18
Arm	-ET^b)	-no RT^c) -RT	-ET⁺RT -ET
Primary outcomes	LRR^d)	BCRFI^e)	invasive or non-invasive IBTR^f)
Actual study start date	2015.03	2018.05	2021.06
Estimated primary completion date	2026.03	2027.09	2026.01
Estimated study completion date	2026.03	2027.12	2041.07