Title

Endocrine Therapy for Hormone Receptor–Positive Metastatic Breast Cancer

Authoring Organization

Publication Month/Year

May 23, 2016

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Women with HR-positive MBC

Target Provider Population

Including primary care physicians, specialists, nurses, social workers, and any other

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management, Treatment

Keywords

endocrine therapy, HR+, Hormone Receptor–Positive, Metastatic Breast Cancer, Advanced Breast Cancer

Source Citation

DOI: 10.1200/JCO.2016.67.1487 Journal of Clinical Oncology 34, no. 25 (September 01, 2016) 3069-3103.

Supplemental Methodology Resources

Data Supplement, Methodology Supplement

Methodology

Number of Source Documents
36
Literature Search Start Date
January 1, 2008
Literature Search End Date
June 30, 2015
Description of External Review Process
The ASCO Clinical Practice Guidelines Committee convened an Expert Panel with multidisciplinary representation in medical oncology, radiation oncology, community oncology, psycho-oncology, nursing, and patient representation. The Expert Panel was led by two Co-Chairs who had primary responsibility for the development and timely completion of the guideline. The Expert Panel members are listed in Data Supplement 6 (online only). The draft clinical practice guideline was distributed to three clinicians who were not members of the Expert Panel for review (Acknowledgment [online-only]). Although the three reviewers were in agreement with the systematic review results, the Expert Panel’s interpretation of the evidence, and the draft recommendations, comments were received concerning the lack of guidance around rebiopsying metastatic tissue and retesting of ER and HER2. In response, the working group added a section covering these to the Introduction. All other comments, both substantive and editorial, were considered by the working group, and changes were made to address all comments as warranted.
Specialties Involved
Family Medicine, Internal Medicine General, Oncology, Medical 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
1.0 Is there an optimal* first-line endocrine therapy regimen for hormone-receptor-positive metastatic breast cancer: 1.1 For postmenopausal women: What is the optimal* sequence and duration? 1.2 Should hormonal therapy be given in combination with other hormone agents or chemotherapy? 1.3 For premenopausal women: What is the optimal* timing of ovarian suppression/ablation? Should all patients have their ovaries suppressed? What is the best partner hormone agent in this setting? 1.4 Are there demonstrated differences between pre- and postmenopausal patients? 2. Is there an optimal* second- or later-line endocrine therapy for hormone-receptor positive metastatic breast cancer? 2.1 Should other treatment or disease-free interval play a role in treatment selection? 2.2 Which hormonal therapy should be offered? 2.3 What are the optimal timing, dose and schedule of treatment? 3. How or should endocrine therapies be used in combination/sequence with: 3.1 mTOR inhibitors (everolimus)? 3.2 CDK 4/6 inhibitors (palbociclib)? 4. Does estrogen/progesterone expression (high versus low expression) impact hormonal therapy considerations and modify recommendations for hormonal therapy, either the recommended agent(s) or dosing details, among pre-, peri-, and postmenopausal women? 5. How does adjuvant treatment affect recommendations for treatment in the metastatic/advanced setting? 6. In which patients or settings is hormonal therapy recommended rather than chemotherapy? 6.1 Is there a role for combined cytotoxic and endocrine therapy? 6.2 What is the optimal duration of treatment with hormonal therapy? 7. Is there a role for additional biomarkers in the selection of treatment for patients for HR+ disease? 7.1 What is the role of genomic profiling/intrinsic sub-types within this population? 8. How does HER2 positivity affect treatment of patients with HR+ metastatic breast cancer? 9. What are the future directions for treatment in this patient population? *Optimal is defined as treatments with demonstrated benefits in both treatment-related outcomes and quality of life outcomes.
Description of Study Criteria
ASCO guidelines are based on systematic reviews of the literature. A protocol for each systematic review defines parameters for a targeted literature search. Additional parameters include relevant study designs, literature sources, types of reports, and pre-specified inclusion and exclusion criteria for literature identified.
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 funds 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