Bone-Modifying Agents in Metastatic Breast Cancer

Publication Date: October 16, 2017
Last Updated: March 27, 2023


  • Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. (Strong Recommendation: EB-H)
    • One BMA is not recommended over another.
    • Options include:
      • denosumab, 120 mg subcutaneously, every 4 weeks;
      • pamidronate, 90 mg intravenously, every 3–4 weeks; or
      • zoledronic acid, 4 mg intravenously, over no less than 15 minutes,
        every 12 weeks or every 3–4 weeks.
  • The analgesic effects of BMAs (denosumab, pamidronate, or zoledronic acid) are modest. They should not be used alone for bone pain.
    (Weak Recommendation: EB-L).
    • The current standard of care for supportive care and pain management should be applied. This can include analgesia, adjunct therapies, radiotherapy, surgery, systemic anti-cancer therapy, and referral to supportive care and pain management.
    • Evidence of a clinically meaningful benefit is insufficient to support the use of one bone-modifying agent over another.


Unchanged from 2011

  • BMAs are recommended for patients with metastatic breast cancer with evidence of bone destruction.
  • One BMA is not recommended over another.
  • Mechanism of action, as well as the potential benefits and harms, should be taken into account when considering long-term use of BMA.
  • In patients with creatinine clearance >60 mL/min, no change in dosage, infusion time, or interval is required.
  • Monitor creatinine level with each intravenous bisphosphonate dose.
  • In patients with creatinine clearance <30 mL/min or on dialysis who may be treated with denosumab, close monitoring for hypocalcemia is recommended.
  • All patients should have a dental examination and preventive dentistry
    before using a BMA.
  • Use of biochemical markers to monitor BMA use is NOT recommended for routine care.

Table 1. Route of Administration, Dose, and Schedule for Bone Modifying Agents

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90 mg

Delivered over no less than 2 hours every 3 or 4 weeks

Zoledronic acid


4 mg

Delivered over no less than 15 minutes every 12 weeks or every 3–4 weeks

Monoclonal antibodies


Subcutaneous injection

120 mg

Every 4 weeks

Recommendation Grading


The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.



Role of Bone-Modifying Agents in Metastatic Breast Cancer

Authoring Organizations

Publication Month/Year

October 16, 2017

Last Updated Month/Year

June 9, 2022

Document Type


External Publication Status


Country of Publication


Target Patient Population

Patients with metastatic breast cancer needing BMAs

Target Provider Population

Medical oncologists, radiation oncologists, surgical oncologists, oncology nurses

Inclusion Criteria

Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant




breast cancer, bone-modifying agent, bone modifying, bone-modifying agents, BMAs, Metastatic Breast Cancer, Breast Cancer

Source Citation

DOI: 10.1200/JCO.2017.75.4614 Journal of Clinical Oncology 35, no. 35 (December 10, 2017) 3978-3986.

Supplemental Methodology Resources

Data Supplement, Methodology Supplement


Number of Source Documents
Literature Search Start Date
January 1, 2011
Literature Search End Date
June 30, 2016
Description of External Review Process
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
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
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