Early Breast Cancer Bisphosphonate Therapy

Scottish Cancer Network: Clinical Management Pathways
NHS National Services Scotland
Scottish Cancer Network logo

This consensus document is not a rigid constraint on clinical practice, but a concept of good practice against which the needs of the individual patient should be considered. It therefore remains the responsibility of the individual clinician to interpret the application of these guidelines, taking into account local service constraints and the needs and wishes of the patient. It is not intended that these consensus documents are applied as rigid clinical protocols.  

Bisphosphonate Use in Early Breast Cancer

In the adjuvant setting, bisphosphonates have been shown in trials to reduce the rate of breast cancer recurrence and improve survival in patients who were postmenopausal at the start of adjuvant treatment. Patients in induced menopause and men may also be considered for treatment. In this situation, 3 years of bisphosphonate treatment is indicated. 

Bisphosphonate therapy should start as soon as possible after surgery and can be given concurrently with, after or before SACT, radiotherapy, endocrine therapy or biological therapy. 

For bisphosphonate use in the metastatic setting, please refer to your local or regional policy. 

Who Should Receive Bisphosphonates?

Bisphosphonates should be considered for: 

  • post-menopausal patients (definition below) with early breast cancer
    • NHS Predict 2-3% clinical decision 
    • NHS Predict >3% advise bisphosphonates 
    • (NHS Predict< 2% not recommend) 
  • induced menopause (ovarian function suppression)* at start of bisphosphonate therapy with same predict criteria as for post menopausal patients  
  • Male patients with high- risk early breast cancer should be considered for bisphosphonate therapy 

*patients with chemotherapy induced menopause but not on ovarian function suppression, should not routinely be offered bisphosphonate therapy. 

NHS Predict is a decision support tool, but other factors should also be taken into consideration when assessing whether a patient should receive bisphosphonates e.g. where a patient opts not to receive SACT or has contra-indications to SACT but would otherwise have been eligible for bisphosphonates, this may still be considered as an option. 

Confirmation of Menopausal Status at Diagnosis

Women can be considered post-menopausal if one of the following definitions are met: 

  • Bilateral surgical oophorectomy 
  • Age >49 and natural amenorrhoea > 2 years 
  • Age <55 natural amenorrhoea of more than 1 year but less than 2 years duration and FSH >25 IU/L and oestradiol within locally defined postmenopausal range* 
  • Age ≥55 and natural amenorrhoea of at least 1 year duration 
  • Patients with an intrauterine device may be considered postmenopausal if FSH >25 IU/L and oestradiol within locally defined postmenopausal range 

*Local laboratory defined post-menopausal range will vary. An acceptable alternative, less conservative, cut-off is <110pmol/l 

Choice of Bisphosphonate

 

1st choice 

IV zoledronic acid 4mg every 6 months for 3 years

Patients receiving IV zoledronic acid should be given Vitamin
D loading dose at first treatment - 100,000iu PO x 1 dose. 

Patients on zoledronic acid should receive calcium and
vitamin D for at least 4 weeks after each dose unless
contra-indicated. The recommended dose is approximately
1000mg calcium and 800i/U vitamin D daily. 

For patients already taking daily vitamin D supplements: 

  • An individual assessment should be made on whether
    they can miss the loading dose when starting zoledronic acid.  
  • Patients should be advised to withhold daily vitamin
    D supplementation for the four weeks they are taking
    calcium and vitamin D combination. 

Patients on oral bisphosphonates – adequate intake of
calcium and vitamin D is important. Patients should receive
supplemental calcium and/or vitamin D if dietary
intake is inadequate.  

Please see local formulary for preparation choice and dosing. 

2nd choice/ patient preference/ service factors 

Oral ibandronate 50mg daily for 3 years 

2nd choice/ patient preference/ service factors 

Sodium Clodronate 1600mg daily for 3 years 

Treatment choice may be influenced by a number of factors, e.g., renal function. Please refer to local prescribing policies for information on prescribing and administration. 

Patients with cancer and on bisphosphonate treatment are at increased risk of osteonecrosis of the jaw and other complications. Please refer to local prescribing policies for recommendations on dental review and patient information to be provided.

References

NICE (2023) Early and locally advanced breast cancer: diagnosis and management [Internet]. Available from: https://www.nice.org.uk/guidance/ng101 [Accessed 11 July 2023] 

Michael Gnant, M.D., Brigitte Mlineritsch, M.D., Walter Schippinger, M.D., Gero Luschin-Ebengreuth, M.D., Sabine Pöstlberger, M.D., Christian Menzel, M.D., Raimund Jakesz, M.D., Michael Seifert, M.D., Michael Hubalek, M.D., Vesna Bjelic-Radisic, M.D., Hellmut Samonigg, M.D., Christoph Tausch, M.D.,et al., for the ABCSG-12 Trial Investigators  Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast Cancer N Engl J Med 2009; 360:679-691. doi: 10.1056/NEJMoa0806285 

Julie R. Gralow , William E. Barlow , Alexander H. G. Paterson, Jieling L. Miao, Danika L. Lew, Alison T. Stopeck, Daniel F. Hayes , Dawn L. Hershman , Mark M. Schubert, Mark Clemons , Catherine H. Van Poznak, Elizabeth C. Dees, James N. Ingle , Carla I. Falkson, Anthony D. Elias, Michael J. Messino, Jeffrey H. Margolis, Shaker R. Dakhil, Helen K. Chew, Kim Z. Dammann, Jeffrey S. Abrams, Robert B. Livingston,† Gabriel N. Hortobagyi Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307 JNCI J Natl Cancer Inst (2020) 112(7): djz215. doi: 10.1093/jnci/djz215 

Marium Ilahi, Laura AG Armas, Robert P Heaney Pharmacokinetics of a single, large dose of cholecalciferol The American Journal of Clinical Nutrition Volume 87, Issue 3, March 2008, Pages 688-691. doi: 10.1093/ajcn/87.3.688 

Editorial Information

Last reviewed: 09/02/2024

Next review date: 09/02/2027

Author(s): Lisa MacLeod on behalf of the Breast SACT subgroup.

Version: 1

Reviewer name(s): Frances Yuille.