Last updated April 19, 2022

Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer

Diagnosis

Newly Diagnosed ER-positive, HER2-negative Breast Cancer

Oncotype DX (21-gene recurrence score)

Recommendation 1.1
If a patient has node-negative breast cancer, the clinician may use Oncotype DX test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , H , S )
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Recommendation 1.2
In the group of patients in Recommendation 1.1 with Oncotype DX score greater than or equal to 26, the clinician should offer chemoendocrine therapy. ( EB , H , S )
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Recommendation 1.3
In the group of patients in Recommendation 1.1 who are 50 years of age or younger with Oncotype DX score 16 to 25, the clinician may offer chemoendocrine therapy. ( EB , I , M )
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Recommendation 1.4
If a patient is postmenopausal and has node-positive breast cancer with 1–3 positive nodes, the clinician may use Oncotype DX test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , H , S )
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Recommendation 1.5
In the group of patients in Recommendation 1.4, the clinician should offer chemoendocrine therapy for those whose Oncotype DX score is greater than or equal to 26. ( EB , H , S )
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Recommendation 1.6
If a patient is premenopausal and has node-positive breast cancer with 1–3 positive nodes, Oncotype DX test should NOT be offered to guide decisions for adjuvant systemic chemotherapy. ( EB , H , M )
Qualifying statement: The genomic assay is prognostic and may be used for shared patient-physician treatment decision making.
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Recommendation 1.7
If a patient has node-positive breast cancer with more than 3 positive nodes, the evidence on the clinical utility of routine Oncotype DX test to guide decisions for adjuvant endocrine and chemotherapy is insufficient to recommend its use. ( IC , Ins, M )
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MammaPrint (70-gene signature)

Recommendation 1.8
If a patient is older than 50 and has high clinical risk breast cancer that is node-negative or node-positive with 1–3 positive nodes, the clinician may use MammaPrint test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , S )
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Recommendation 1.9
If a patient is 50 years of age or younger and has high clinical risk, node-negative or node-positive with 1–3 positive nodes breast cancer, the clinician should NOT use the MammaPrint test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , H , S )
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Recommendation 1.10
If a patient has low clinical risk, regardless of age, the evidence on clinical utility of routine MammaPrint test is insufficient to recommend its use. ( EB , I , M )
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Recommendation 1.11
If a patient has node-positive breast cancer with more than 3 positive nodes, the evidence on the clinical utility of routine MammaPrint test to guide decisions for adjuvant endocrine and chemotherapy is insufficient to recommend its use. ( IC , Ins, S )
Qualifying statement: The genomic assay is prognostic and may be used for shared patient-physician treatment decision making.
614

EndoPredict (12-gene risk score)

Recommendation 1.12
If a patient is postmenopausal and has breast cancer that is node-negative or node-positive with 1–3 positive nodes, the clinician may use EndoPredict test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , M )
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Recommendation 1.13
If a patient is premenopausal and has breast cancer that is node-negative or node-positive with 1–3 positive nodes, the clinician should NOT use EndoPredict test to guide decisions for adjuvant endocrine and chemotherapy. ( IC , Ins, M )
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Recommendation 1.14
If a patient has breast cancer with more than 3 positive nodes, evidence on the clinical utility of routine use of EndoPredict test to guide decisions for adjuvant endocrine and chemotherapy is insufficient. ( EB , I , M )
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Prosigna (PAM50)

Recommendation 1.15
If a patient is postmenopausal and has breast cancer that is node-negative, the clinician may use the Prosigna test to guide decisions for adjuvant systemic chemotherapy. ( EB , I , M )
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Recommendation 1.16
If a patient is premenopausal, and has node-negative or node-positive breast cancer the clinician should NOT use the Prosigna test to guide decisions for adjuvant systemic chemotherapy. ( IC , Ins, M )
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Recommendation 1.17
If a patient is postmenopausal and has node-positive breast cancer with 1–3 positive nodes, the evidence is inconclusive to recommend the use of Prosigna test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , M )
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Recommendation 1.18
If a patient has node-positive breast cancer with more than 3 positive nodes, evidence on the clinical utility of routine use of Prosigna test to guide decisions for adjuvant endocrine and chemotherapy is insufficient to recommend its use. ( IC , Ins, S )
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Mammostrat

There is insufficient evidence to recommend use of Mammostrat to guide decisions about adjuvant endocrine and chemotherapy. ( EB , I , M )
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Breast Cancer Index (BCI)

If a patient has ER-positive, HER2-negative, node-negative breast cancer, the clinician may use the BCI to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , M )
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If a patient has ER-positive, HER2-negative, node-positive breast cancer, the clinician should NOT use the BCI to guide decisions about adjuvant endocrine and chemotherapy. ( IC , Ins, S )
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Ki67

Recommendation 1.19
If a patient is postmenopausal and has stage I–II breast cancer, the clinician may use Ki67 expression in conjunction with other clinical and pathologic parameters to guide decisions on adjuvant endocrine and chemotherapy when multigene assays are not available. Ki67 expression levels are most informative for prognosis when the level is <5% (low proliferation) or >30% (high proliferation) because technical reliability of distinguishing values within this range is limited. ( EB , I , M )
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Recommendation 1.20
If a patient is postmenopausal and has breast cancer, there is insufficient evidence to use baseline Ki67 expression or Ki67 level after 2 weeks of neoadjuvant aromatase inhibitor (AI) therapy to guide decisions on adjuvant endocrine and chemotherapy. ( IC , L , W )
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Recommendation 1.21
Despite the limitations associated with Ki67 testing, a patient with node-positive breast cancer with a high risk of recurrence and a Ki67 score of ≥20% as determined by an FDA-approved test may be offered two years of abemaciclib plus endocrine therapy. ( EB , I , S )
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Immunohistochemistry 4 (IHC4)

Recommendation 1.22
If a patient has node-negative or node-positive breast cancer with 1–3 positive nodes, the clinician may use IHC4 test to guide decisions for adjuvant endocrine and chemotherapy if the assay has been validated in the performing laboratory and if multigene assays are not available. ( EB , I , M )
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uPA and PAI-1

If a patient has ER-positive, HER2-negative (node-negative) breast cancer, the clinician may use the uPA and PAI-1 to guide decisions about adjuvant endocrine and chemotherapy. ( EB , H , W )
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If a patient has HER2-positive breast cancer or triple-negative breast cancer (TNBC), the clinician should NOT use the uPA and PAI-1 to guide decisions about adjuvant endocrine and chemotherapy. ( IC , Ins, W )
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Extended Endocrine Therapy For ER Receptor-positive HER2-negative Breast Cancer

Oncotype DX, EndoPredict, Prosigna, Ki67, or IHC4

Recommendation 1.23
If a patient has node-negative breast cancer and has had 5 years of endocrine therapy without evidence of recurrence, there is insufficient evidence to use Oncotype DX, EndoPredict, Prosigna, Ki67, or IHC4 tests to guide decisions about extended endocrine therapy. ( EB , I , M )
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BCI

Recommendation 1.24
If a patient has node-negative or node-positive with 1–3 positive nodes breast cancer and has been treated with 5 years of primary endocrine therapy without evidence of recurrence, the clinician may offer BCI test to guide decisions about extended endocrine therapy with either tamoxifen, an AI, or a sequence of tamoxifen followed by AI. ( EB , I , M )
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Recommendation 1.25
If a patient has node-positive breast cancer with more than 3 positive nodes and has been treated with 5 years of primary endocrine therapy without evidence of recurrence, there is insufficient evidence to use BCI test to guide decisions about extended endocrine therapy with either tamoxifen, an AI, or a sequence of tamoxifen followed by AI. ( EB , I , S )
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Clinical Treatment Score post-5 Years (CTS5)

Recommendation 1.26
If a patient is postmenopausal and had invasive breast cancer and is recurrence free after 5 years of adjuvant endocrine therapy, the CTS5 web tool may be used to calculate the estimated risk of late recurrence (recurrence between years 5–10), that could assist in decisions about extended endocrine therapy. ( EB , I , M )
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HER2-positive Breast Cancer or TNBC

Oncotype DX, EndoPredict, MammaPrint, BCI, Prosigna, Ki67, or IHC4

Recommendation 1.27
If a patient has HER2-positive breast cancer or TNBC, the clinician should NOT use multiparameter gene expression or protein assays (Oncotype DX, EndoPredict, MammaPrint, BCI, Prosigna, Ki67, or IHC4) to guide decisions for adjuvant endocrine and chemotherapy. ( IC , Ins, S )
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Emerging Biomarkers

Tumor-Infiltrating Lymphocytes (TILs)

Recommendation 1.28
If a patient has node-negative or node-positive ER-positive, HER2-positive, or TNBC, the clinician should NOT use TILs test to guide decisions for (neo)adjuvant endocrine and chemotherapy. ( IC , Ins, S )
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PD-L1 Testing 

Recommendation 1.29
If a patient has node-negative or node-positive ER-positive, HER2-positive, or TNBC, the clinician should NOT use PD-L1 testing to guide decisions for (neo)adjuvant endocrine and chemotherapy. ( EB , H , S )
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Circulating Tumor Cells (CTC)

Recommendation 1.30
If a patient has node-negative or node-positive ER-positive, HER2-positive, or TNBC, the clinician should NOT use CTC test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , S )
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Circulating Tumor DNA (ctDNA)

Recommendation 1.31
If a patient has node-negative or node-positive ER-positive, HER2-positive, or TNBC, the clinician should NOT use ctDNA test to guide decisions for adjuvant endocrine and chemotherapy. ( EB , I , S )
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Recommendation Grading

Overview

Title

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer

Authoring Organization

Publication Month/Year

April 19, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Women with early-stage invasive breast cancer being considered for adjuvant systemic therapy

Target Provider Population

Medical, surgical, and radiation oncologists; oncology nurses and physician assistants; pathologists; general practitioners

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Physician assistant, physician, nurse practitioner, nurse, laboratory technician

Scope

Assessment and screening

Keywords

Oncotype DX, Breast Cancer Biomarkers

Source Citation

Fabrice A, Ismaila N, Allison KH, et al. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2022 April 19. doi: 10.1200/JCO.22.00069