Endocrine Therapy for Breast Cancer Risk Reduction
Publication Date: September 3, 2019
Last Updated: March 14, 2022
Recommendations
Tamoxifen
Should be discussed as an option to reduce the risk of invasive BC, specifically ER-positive BC,inpremenopausalwomenwho are >35 years of age with a 5-year projected absolute BC risk >1.66% or with LCIS. Risk reduction benefit continues for at least 10 years.
Is not recommended for use in women with a history of deep vein thrombosis,pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization.
Is not recommended for women who are pregnant, women who may become pregnant, or nursing mothers.
Is not recommended in combination with hormone therapy.
Follow-up should include a timely workup of abnormal vaginal bleeding.
Discussions with patients and health care providers should include both the risks and benefits of tamoxifen in the preventive setting.
Dosage: 20 mg/day orally for 5 years.
(EB, S)
7251
Raloxifene
Should be discussed as an option to reduce the risk of invasive BC, specifically ER-positive BC, in postmenopausal women who are>35yearsofagewitha5-yearprojectedabsoluteBCrisk >1.66% or with LCIS.
May be used longer than 5 years in women with osteoporosis, in whom BC risk reduction is a secondary benefit.
Should not be used for BC risk reduction in premenopausal women.
Is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack, or during prolonged immobilization.
Discussions with patients and health care providers should include both the risks and benefits of raloxifene in the preventive setting.
Dosage: 60 mg/day orally for 5 years.
(EB, S)
7251
Exemestane
Should be discussed as an alternative to tamoxifen and/or raloxifene to reduce the risk of invasive BC, specifically ER-positive BC, in postmenopausal women = 35 years of age with a 5-yearprojected absolute BC risk = 1.66% or with LCIS or atypical hyperplasia.
Should not be used for BC risk reduction in premenopausal women.
Discussions with patients and health care providers should include both the risks and benefits of exemestane in the preventive setting
Dosage: 25 mg/day orally for 5 years.
(EB, M)
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Anastrozole
Anastrozole (1 mg/day orally for 5 years) should be discussed as an alternative to tamoxifen, raloxifene, or exemestane to reduce the risk of invasive BC in postmenopausal women at increased risk of developing BC.
Women most likely to benefit from endocrine therapy are those with one of more of the following: a diagnosis of atypical (ductal or lobular) hyperplasia or LCIS, an estimated 5-year risk (NCI BCRAT) of at least 3%, a 10-year risk (IBIS/Tyrer-Cuzick Risk Calculator) of at least 5%, or a relative risk of at least four times the population risk for their age group if their age is 40 to 44 years or two times the population risk for their age group if their age is 45 to 69 years.
Clinicians should not prescribe anastrozole, exemestane, or raloxifene for BC risk reduction in premenopausal women.
Discussions between patients and health care providers should include both the benefits and risks of anastrozole along with the other approved drugs for risk reduction based on menopausal status.
Prior to initiating an aromatase inhibitor, clinicians should evaluate patients for baseline fracture risk and measure bone mineral density. Multiple studies have reported an increased rate of bone loss in women treated with aromatase inhibitors. Clinicians should use anastrozole with caution in postmenopausal women with moderate bone mineral density loss, and if it is used, they should consider the use of bone-protective agents such as bisphosphonates and RANKL inhibitors. All patients receiving aromatase inhibitors should be encouraged to exercise regularly and take adequate calcium and vitamin D supplements. A history of osteoporosis and/or severe bone loss is a relative contraindication for the use of anastrozole. In IBIS-II, women with severe osteoporosis (T score < -4 or more than two vertebral fractures) were excluded. Other endocrine preventive therapies that do not reduce bone density, such as tamoxifen or raloxifene, are also available for this group of women.
Clinicians should also inform women of the possibility of joint stiffness, arthralgias, vasomotor symptoms, hypertension, dry eyes, and vaginal dryness while taking anastrozole.
(EB, S)
7251
Recommendation Grading
Overview
Title
Use of Endocrine Therapy for Breast Cancer Risk Reduction
To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction.
Target Patient Population
Women without a personal history of breast cancer who are at increased risk of developing the disease
Target Provider Population
Medical oncologists, surgical oncologists, gynecologists, primary care physicians, and general practitioners
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.
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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.
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Specialties Involved
Family Medicine, Internal Medicine General, Obstetrics And Gynecology, Oncology, Medical Oncology, Surgical Oncology, Oncology, Oncology
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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.
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List of Questions
See full text
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Description of Study Criteria
See supplement.
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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.
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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.
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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.
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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.
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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.
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Description of Funding Source
ASCO provides funding for Guideline Development.
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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.