Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer
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Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients’ quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.
KeywordsBone loss Bone metastasis Postmenopausal Antitumor effect Adjuvant
Compliance with Ethical Standards
Conflict of Interest
Stephanie Strobl declares that she has no conflict of interest. Kerstin Wimmer has received a congress fee from Pfizer. Ruth Exner declares that she has no conflict of interest. Yelena Devyatko declares that she has no conflict of interest. Michael Bolliger declares that he has no conflict of interest. Florian Fitzal has received financial support for meetings from Novartis, Roche, Pfizer, and AstraZeneca, and has received honoraria from Roche and Pfizer. Michael Gnant has received research support through grants from AstraZeneca, Roche, Novartis, and Pfizer; and has received compensation from AstraZeneca, Roche, Novartis, Pfizer, Accelsiors, Amgen, Celgene, and OBI Pharma for service as a consultant.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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- 2.Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol. 2014;32(21):2255–69.PubMedPubMedCentralCrossRefGoogle Scholar
- 3.Dubsky PC, Jakesz R, Mlineritsch B, Postlberger S, Samonigg H, Kwasny W, et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012;30(7):722–8.PubMedCrossRefGoogle Scholar
- 4.Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007;99(24):1845–53.PubMedCrossRefGoogle Scholar
- 5.Bartlett JMS, Ahmed I, Regan MM, Sestak I, Mallon EA, Dell’Orto P, et al. HER2 status predicts for upfront AI benefit: A TRANS-AIOG meta-analysis of 12,129 patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2. Eur J Cancer 2017; 79:129–138.Google Scholar
- 6.• Jacobs C, Amir E, Paterson A, Zhu X, Clemons M. Are adjuvant bisphosphonates now standard of care of women with early stage breast cancer? A debate from the Canadian Bone and the Oncologist New Updates meeting. J Bone Oncol. 2015;4(2):54–8. This recent Work shows the benefit of bisphosphonates in relation to the estrogen level and the menopausal status.PubMedPubMedCentralCrossRefGoogle Scholar
- 7.•• Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. New England J Med. 2009;360(7):679–91. The ABCSG-12 trial demonstrated a significant outcome benefit for advuvant zoledronic acid in premenopausal hormone-receptor positive breast cancer patients on ovarian function suppression therapy.CrossRefGoogle Scholar
- 8.Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011;12(7):631–41.PubMedCrossRefGoogle Scholar
- 9.• Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Knauer M, Moik M, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015;26(2):313–20. This study underlines the superior effect of adjuvant bisphosphonate therapy in woman with early-stage breast cancer, who have a low estrogen level induced through ovarian function suppression or by nature.PubMedCrossRefGoogle Scholar
- 18.•• Early Breast Cancer Trialists’ Collaborative G. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386(10001):1353–61. The EBCTCG meta-analysis confirms a significant outcome benefit for adjuvant bisphosphonates in postmenopausal women, both in terms of breast cancer recurrences and overall survival.CrossRefGoogle Scholar
- 20.Hue TF, Cummings SR, Cauley JA, Bauer DC, Ensrud KE, Barrett-Connor E, et al. Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Intern Med. 2014;174(10):1550–7.PubMedPubMedCentralCrossRefGoogle Scholar
- 21.• Early Breast Cancer Trialists’ Collaborative G, Dowsett M, Forbes JF, Bradley R, Ingle J, Aihara T, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–52. AI shows a significant benefit on overall survival compared with tamoxifen; this makes bone protection with bisphosphonate an important issue.CrossRefGoogle Scholar
- 24.Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. The Lancet Oncology. 2008;9(9):840–9.PubMedCrossRefGoogle Scholar
- 28.Diel IJ, Jaschke A, Solomayer EF, Gollan C, Bastert G, Sohn C, et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol: Off J Eur Soc Med Oncol. 2008;19(12):2007–11.CrossRefGoogle Scholar
- 29.Paterson AH, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, et al. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. The Lancet Oncol. 2012;13(7):734–42.PubMedCrossRefGoogle Scholar
- 42.Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol: Off J Eur Soc Med Oncol. 2013;24(2):398–405.CrossRefGoogle Scholar
- 44.Hadji P, Aapro MS, Body JJ, Gnant M, Brandi ML, Reginster JY, et al. Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. 2017;7:1–12.PubMedPubMedCentralCrossRefGoogle Scholar
- 45.•• Dhesy-Thind S, Fletcher GG, Blanchette PS, Clemons MJ, Dillmon MS, Frank ES, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: a Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol: Off J Am Soc Clin Oncol. 2017;35(18):2062–81. The most recent ASCO guideline suggests adjuvant bone-targeted therapy for all breast cancer patients who are postmenopausal or premenopausal women on ovarian function suppression therapy.CrossRefGoogle Scholar
- 47.Cramer JA, Lynch NO, Gaudin AF, Walker M, Cowell W. The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France. Clin Ther. 2006;28(10):1686–94.PubMedCrossRefGoogle Scholar
- 48.Julie Gralow, WEB, Alexander H. G. Paterson, Danika Lew, Alison Stopeck, Daniel F. Hayes ... Dawn L. Hershman, et al. SWOG S0307 phase III trial of bisphosphonates as adjuvant therapy in primary breast cancer: comparison of toxicities and patient-stated preference for oral versus intravenous delivery. J Clin Oncol 32, no 15_suppl (May 2014) 558–558. 2014.Google Scholar
- 52.Berenson JR, Vescio RA, Rosen LS, VonTeichert JM, Woo M, Swift R, et al. A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases. Clin Cancer Res: Off J Am Assoc Cancer Res. 2001;7(3):478–85.Google Scholar
- 60.Gnant M PG, Dubsky PC, Hubalek M, Greil R, Jakesz R, Wette V, et al. The impact of adjuvant denosumab on disease-free survival: results from 3425 postmenopausal patients of the ABCSG-18 trial. San Antonio Breast Cancer Symposium: 2015 Dec 8–12; San Antonio, TX2015.Google Scholar
- 61.•• Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433–43. ABCSG-18 demonstrates in the primary end point analysis that adjuvant denosumab (60 mg s.c. twice yearly) reduced treatment-induced clinical fractures by 50% in postmenopausal women on adjuvant aromatase inhibitor treatment.PubMedCrossRefGoogle Scholar