Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG

Abstract

Background: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population.

Patients and methods: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses. Individual trials identified were assessed for their level of evidence based on design, size, follow-up, and evaluation of safety, as well as the impact of bone directed treatments on breast cancer outcomes.

Results: New evidence was combined with the existing recommendations to provide an updated joint position statement regarding fracture risk assessment and implementation of bone-directed therapy.

Conclusion: Current published literature, including recent clinical trial reports, systematic reviews and meta-analyses, continue to affirm the high risk of fractures in women with breast cancer who are receiving adjuvant AI treatment, a risk which has been observed to increase with the commonly used approach of extended duration AI therapy (>5 years). Risk factors for fracture and risk assessment in this patient population as well as the most suitable treatment modalities have been updated. Finally, the influence of bone protective treatments on breast cancer outcomes such as incidence of bone metastasis and breast cancer related overall survival have been included.

Keywords: Aromatase Inhibitor; Bisphosphonate; Breast cancer; Denosumab; Fracture; Osteoporosis.

Fig. 1

Recommended algorithm for use of bone-targeted treatments in early breast cancer. Adapted from Coleman et al, 2020 [12]. ^a If not clinically assessable (i.e. hysterectomy/IUD) then ensure age > 55 and/or serum FSH is in postmenopausal range (patient must not be receiving concurrent therapies that can affect the hypophyseal–pituitary–gonadal axis). ^b Patients already on weekly oral bisphosphonates for osteoporosis should be considered for a treatment change and follow algorithm. ^c Include vitamin D3 800–2000 IU (plus calcium 1000 mg daily if low calcium diet). ^d May switch from oral to i.v. therapy or vice versa if tolerability issues. ^e Daily oral ibandronate (50 mg/day) or clodronate (1,600 mg/day) as in the SWOG S0307 trial [85]. Duration of treatment is not well defined and may vary between 2 and 5 years. Abbreviations: BTA, bone-targeted agent; CTIBL, cancer treatment-induced bone loss; i.v., intravenous; IUD, intrauterine device; FSH, follicle-stimulating hormone.

Fig. 2

Recommended algorithm for managing bone health in women receiving aromatase inhibitor therapy for breast cancer. Adapted from Hadji et al, 2017 [10] and Coleman et al, 2020 [12]. ^a Includes AIs and ovarian suppression therapy/oophorectomy. ^b If patients experience an annual decrease in BMD of ≥ 10 % at any site (or ≥ 4–5 % in patients who were osteopenic at baseline) using the same DXA absorptiometry machine, secondary causes of bone loss such as vitamin D deficiency should be evaluated and antiresorptive therapy initiated. Use the lowest T-score from spine or hip. ^c Either denosumab (60 mg every 6 months) or six-monthly intravenous zoledronate (4 mg) as first-line treatment (for the duration of endocrine treatment/together typically for up to 5 years). Discontinuation of denosumab should be followed up by an appropriate antiresorptive. ^d Weekly oral alendronate (70 mg) or risedronate (35 mg) or monthly oral ibandronate (150 mg) for the duration of endocrine treatment/typically for up to 5 years. Abbreviations: AI, aromatase inhibitor; BMD, bone mineral density; BMI, body mass index.