Abstract PS1-07-18: Assessment of the Risk of Humeral Head Fractures after Radiation Therapy

Abstract Background: As 1 in 8 American women are diagnosed with invasive breast cancer in their lifetime and with the shift toward breast-conserving surgery, radiation therapy plays a critical role in breast cancer treatment. However, the humerus often receives off-target radiation, and post-radiation humeral head fractures are a rare but serious adverse effect of treatment, as surgical repair of hypovascularized bone is difficult. In addition, adjuvant aromatase inhibitors increase the risk of fracture. A previous study of 159 patients estimated that 6.06% of patients develop humeral head fractures ipsilateral to the treated breast. Therefore, we retrospectively analyzed 399 patients with breast cancer to identify risk factors for humeral head fractures. Methods: Our single-center study included patients with a diagnosis of in situ carcinoma or invasive breast cancer. The primary endpoint was development of humeral head fracture ipsilateral to the treated breast. We used logistic regression to elucidate associations between development of humeral head fractures and radiation exposure, usage of boost radiation, and hormonal therapy among other studied variables. In addition, we used Cox proportional hazards regression to temporally study the development of humeral head fractures. Results: Among the 399 patients, the mean age at biopsy was 61.04 (SEM: 0.61) with a mean follow-up time of 4.56 (SEM: 0.23). Of the 399 malignancies, invasive ductal carcinoma (IDC; 84%), invasive lobular carcinoma (ILC; 7%), and ductal carcinoma in situ (DCIS; 6%) were the most common subtypes. 2.5% of the 399 patients did not receive radiation. Of the patients receiving radiation, the mean dosage was 39.08 (SEM: 0.51). 42.6% received chemotherapy, and 79.2% received hormonal therapy. 41 patients (10.3%) developed humeral head fractures on the treated side, and 18 of the 41 had fractures were secondary to trauma.In multivariable analysis, women receiving radiation therapy were not significantly more likely to develop humeral head fractures (OR: 0.96; 95% CI: [0.92, 1.01], p=0.11). The presence of trauma was not associated with humeral head fractures. Patients with longer follow-up were more likely to develop humeral fractures (OR: 1.03, 95% CI: [1.003, 1.07], p=0.03). Likewise, on Cox proportional hazards test, radiation therapy was not associated with development of humeral head fractures (HR: 0.44, 95% CI: [0.18, 1.04], p=0.06). Usage of hormonal therapy (HR: 0.36, 95% CI: [0.52, 2.11], p=0.89) and chemotherapy (HR: 0.37, 95% CI: [0.29, 28.07], p=0.83) were also not associated with development of humeral head fractures. Likewise, lumpectomy (HR: 1.18, 95% CI: [0.54, 56.41], p=0.15) and mastectomy (HR: 1.17, 95% CI: [0.29, 28.07], p=0.37) were not associated with humeral head fractures. Conclusion: Our study suggests that radiation therapy, as well as surgical approaches such as lumpectomy and mastectomy, are not significantly associated with the development of humeral head fractures. Furthermore, the use of hormonal therapies, despite their known association with bone density loss, was not linked to increased fracture risk in our cohort. Overall, these findings support the safety of current standard therapies for breast cancer with humeral head fracture risk. Citation Format: M. Tjauw, J. Oh, D. Han, P. Pitts, P. Pius, C. Henson, A. Johnston, . Assessment of the Risk of Humeral Head Fractures after Radiation Therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-07-18.