Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer
Publication Date: November 29, 2018
Last Updated: December 15, 2022
Treatment
Updated Recommendations on Extended Therapy
Many women with node-negative breast cancer are potential candidates for and may be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. However, as the recurrence risk is lower, the benefits are likely narrower for such patients. Women with low-risk node-negative tumors should not routinely be offered extended therapy. (, , )
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Women with node-positive breast cancer should be offered extended AI therapy for up to a total of 10 years of adjuvant endocrine treatment. (, , )
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Women receiving extended adjuvant endocrine therapy should receive no more than 10 years of total treatment. (, , )
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As prevention of secondary or contralateral breast cancers is a major benefit of extended AI therapy, the risk of second breast cancers (or not) based on prior therapy should inform the decision to pursue extended treatment. (, , )
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Extended therapy carries ongoing risks and side effects, which should be weighed against the potential absolute benefits of longer treatment in a shared decision-making process between the clinical team and the patient. (, , )
Qualifying Statement:
To date, none of the studies has shown improvement in overall survival with longer duration AI therapy. As such, the recommendations on extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers.
To date, none of the studies has shown improvement in overall survival with longer duration AI therapy. As such, the recommendations on extended adjuvant AI therapy are based on benefits that include prevention of distant recurrence and prevention of second breast cancers.
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Recommendations on Ovarian Suppression
The Panel recommends that higher risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy while lower risk patients should not. (, , )
Qualifying Statement:
The Panel notes that two prospective studies did not show overall clinical benefit for the addition of ovarian suppression to tamoxifen in premenopausal, ER-positive breast cancer. However, in a large subset of women with higher risk cancers, nearly all of whom received chemotherapy but remained premenopausal, ovarian suppression added to tamoxifen reduced the risk of breast cancer recurrence. Because of the design of the clinical trials, there are few definitive criteria by which to define risk.
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Women with Stage II or Stage III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression in addition to endocrine therapy. (, , )
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Women with Stage I or II breast cancers at higher risk of recurrence, who might consider chemotherapy, may also be offered ovarian suppression in addition to endocrine therapy. (, , )
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Women with Stage I breast cancers not warranting chemotherapy should receive endocrine therapy but not receive ovarian suppression. (, , )
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Women with node-negative cancers 1 centimeter or less (T1a, T1b) should receive endocrine therapy but not receive ovarian suppression. (, , )
Qualifying Statements:
The standard duration of ovarian suppression in the included trials was 5 years. With no comparative data available on alternative durations, the Panel supports ovarian suppression for 5 years.
To date there is no adequate evidence for assessing the benefit of adjuvant ovarian suppression in women at sufficient risk to warrant chemotherapy compared with 10 years of tamoxifen.
There is no current role for ovarian suppression as adjuvant therapy in ER-negative breast cancers.
There are substantial side effects to ovarian suppression. Clinicians and patients should consider the tradeoffs of side effects when choosing ovarian suppression.
The long term effects of ovarian suppression on breast cancer risk and survival are not yet established.
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Ovarian suppression may be administered with either tamoxifen or an aromatase inhibitor. (, , )
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Recommendation Grading
Overview
Title
Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
November 29, 2018
Last Updated Month/Year
October 2, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment.
Target Patient Population
Postmenopausal women with stages I to III hormone receptor–positive breast cancer.
Target Provider Population
Medical, surgical, and radiation oncologists; oncology nurses and physician assistants; general practitioners
Inclusion Criteria
Female, Adult, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment, Management
Keywords
endocrine therapy, hormone receptor positive breast cancer, Adjuvant Therapy, HR+, Hormone Receptor–Positive, Advanced Breast Cancer
Source Citation
DOI: 10.1200/JCO.18.01160 Journal of Clinical Oncology 37, no. 5 (February 10, 2019) 423-438.
Supplemental Methodology Resources
Methodology
Number of Source Documents
6
Literature Search Start Date
February 14, 2017
Literature Search End Date
February 28, 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.
Specialties Involved
Family Medicine, Internal Medicine General, Oncology, Medical Oncology, Surgical Oncology, Radiation Oncology, Oncology, 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
Does extended adjuvant therapy, including aromatase inhibitors (AIs), after 5 years of sequential endocrine therapy improve clinically meaningful outcomes (disease-free survival, overall survival, quality of life, and toxicity) in postmenopausal women with hormone receptor–positive early breast cancer?
Description of Study Criteria
Articles were selected for inclusion in the systematic review of the evidence if they met the following criteria:
Published journal articles from the medical literature
Phase III RCTs
Meeting abstracts, if presentations/posters were available
Written language, English only
Systematic reviews with or without meta-analyses
Study population of postmenopausal women
Articles were excluded from the systematic review if they were (1) other reviews (consensus, narrative, expert panel, guidelines); (2) editorials, commentaries, letters, news articles, case reports; or (3) published in a non-English language. Ratings for the type of recommendation and strength of the evidence and potential bias are provided with each recommendation (see the Methodology Supplement for rating definitions).
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.
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 Supplements 1.
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