Abstract 279P
Background
Bone modifying agents (BMAs) such as Zoledronic acid (ZA) and Denosumab (Dmab) are indicated in metastatic breast cancer (MBC) with bone involvement to prevent skeletal-related events.1 In the early breast cancer (EBC) setting, bisphosphonates reduce distant/bone recurrence and breast cancer mortality in post-menopausal women.2 Although well tolerated, BMAs carry a risk of severe adverse events such as medication-related osteonecrosis of the jaw (MRONJ). Our aim was to assess the incidence, risk factors and management of MRONJ in breast cancer patients receiving ZA and Dmab at our centre.
Methods
All breast cancer patients, who received at least one dose of ZA or Dmab between 2015 and 2020, were retrospectively identified using Chemocare v6. Electronic records were reviewed till 15/01/2024 for ONJ incidence. Clinical details were collated using Microsoft Excel. SPSS v29.0.2 was utilised for statistical analysis.
Results
455 patients received at least 1 dose of ZA or Dmab. 102 (22.4%) and 353 (77.6%) had diagnoses of EBC and MBC respectively (Table). 17 (3.7%) patients developed MRONJ. Majority were MBC patients receiving palliative monthly Dmab; 1 patient had switched from Dmab to ZA. Mean duration of BMA treatment was 2.2 years (10 months – 4 years). Concurrent systemic treatments included chemotherapy, 3 (17.6%), anti-HER2 directed therapy, 2 (11.8%), hormones, 7 (41.2%) and Cyclin-dependent kinase 4/6 inhibitors, 5 (29.4%). Presenting symptoms included jaw pain, infection and paraesthesia. Orthopantomogram and Computed Tomography were utilised in confirming diagnosis. The mandible was the most common site affected (52.9%). Table: 279P
Baseline characteristics, risk factors and management
| Characteristic | Whole cohort N=455 | Developed ONJ N=17 |
| Mean age (range) – yr | 65 (33-97) | 69 (49-86) |
| Female sex | 454 (99.7%) | 17 (100%) |
| Diagnosis | ||
| EBC | 102 (22.4%) | - |
| MBC | 353 (77.6%) | 17 (100%) |
| Bone modifying agent | ||
| ZA | 117 (25.7%) | - |
| Dmab | 334 (73.4%) | 16 (94.1%) |
| Dmab -> ZA | 3 (0.67%) | 1 (5.9%) |
| ZA -> Dmab | 1 (0.22%) | - |
| Risk factors | ||
| Dental Intervention | 10 (58.8%) | |
| Hypocalcaemia | 3 (17.6%) | |
| Diabetes Mellitus | 3 (17.6%) | |
| Current Smoker | 1 (5.9%) | |
| Management | ||
| Conservative | 11 (64.7%) | |
| Additional intervention | 4 (23.5%) | |
| Unknown | 2 (11.8%) | |
| BMA discontinued | ||
| Yes | 15 (88.2%) | |
| No | 2 (11.8%) | |
| Systemic treatment | ||
| Continued | 15(88.2%) | |
| Discontinued | 1 (5.9%) | |
| Switched to alternative | 1 (5.9%) |
Conclusions
Incidence of MRONJ is in keeping with published literature. Dental intervention during BMA treatment was our principal risk factor. High-level evidence regarding drug holidays prior to dental intervention is required.3, 4:
References: 1. Goldvaser, H. and Amir, E., 2019. Role of bisphosphonates in breast cancer therapy. Current treatment options in oncology, 20, pp.1-17. 2. Early Breast Cancer Trialists' Collaborative Group, 2015. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. The Lancet, 386(10001), pp.1353-1361. 3. Ruggiero, S.L., Dodson, T.B., Aghaloo, T., Carlson, E.R., Ward, B.B. and Kademani, D., 2022. American Association of Oral and Maxillofacial Surgeons’ position paper on medication-related osteonecrosis of the Jaws—2022 update. Journal of oral and maxillofacial surgery, 80(5), pp.920-943. 4. Ottesen, C., Schiodt, M. and Gotfredsen, K., 2020. Efficacy of a high-dose antiresorptive drug holiday to reduce the risk of medication-related osteonecrosis of the jaw (MRONJ): A systematic review. Heliyon, 6(4).
Legal entity responsible for the study
Breast Team - Oncology Department, University Hospitals of Leicester NHS Trust.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.