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

Publication Date: April 19, 2022
Last Updated: April 19, 2022

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 )
614
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 )
614
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 )
614
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 )
614
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 )
614
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.
614
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 )
614

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 )
614
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 )
614
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 )
614
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 )
614
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 )
614
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 )
614

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 )
614
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 )
614
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 )
614
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 )
614

Mammostrat

There is insufficient evidence to recommend use of Mammostrat to guide decisions about adjuvant endocrine and chemotherapy. ( EB , I , M )
614

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 )
614
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 )
614

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 )
614
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 )
614
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 )
614

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 )
614

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 )
614
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 )
614

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 )
614

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 )
614
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 )
614

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 )
614

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 )
614

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 )
614

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 )
614

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 )
614

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 )
614

Recommendation Grading

Overview

Title

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

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

April 19, 2022

Last Updated Month/Year

November 7, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

Provide more precise guidelines on how to use previously endorsed genomic tests and to provide recommendations on the use of new biomarkers to guide endocrine and chemotherapy recommendations in individuals with ER-positive, HER2-negative tumors, and in those with HER2-positive or triple-negative breast cancer (TNBC).

Target Patient Population

Women with early-stage invasive breast cancer being considered for adjuvant endocrine and chemotherapy.

Target Provider Population

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

PICO Questions

  1. For patients with early-stage ER-positive, HER2-negative breast cancer, which biomarkers should be used to guide decisions on adjuvant endocrine and chemotherapy for a newly diagnosed cancer or in the extended setting?

  2. For patients with early-stage HER2-positive breast cancer, which biomarkers should be used to guide decisions on adjuvant endocrine and chemotherapy?

  3. For patients with early-stage triple-negative breast cancer, which biomarkers should be used to guide decisions on adjuvant chemotherapy?

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Laboratory technician, nurse, nurse practitioner, physician, physician assistant

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

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
92
Literature Search Start Date
January 1, 2017
Literature Search End Date
December 31, 2018
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 to 3‐week period. Guideline recommendations available for open comment are posted on asco.org/open‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Oncology, Pathology, Clinical Pathology, Medical Oncology, Radiation Oncology, Pathology, Oncology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See Full Text
Description of Study Criteria
See Supplement
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100