Can Breast Cancer Receptor Status Predict Pain Response in Palliative Radiation for Bone Metastases?

Abstract

Breast cancer receptor status is predictive for local control following adjuvant radiotherapy (RT). The impact of receptor status on the clinical response to palliative RT for metastatic disease is not known. The purpose of this study was to investigate the significance of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor 2 (HER2) status on the subjective response of palliative RT for patients with breast cancer bone metastases. A retrospective analysis was conducted of prospectively collected patient reported outcomes (PRO) for breast cancer patients treated with palliative RT for bone metastases from 2015 to 2017. The PRO questionnaire scored pain severity, level of function, and symptom frustration at baseline and at 4 weeks following palliative RT. Patients were identified as having at least a partial improvement in PRO (≥1 improvement in score) or complete improvement (final score = 0) or no improvement. Patient demographics, tumor characteristics, systemic treatment information, and RT characteristics were collected. Patients were divided into 4 cohorts for analysis: Luminal A (ER+, HER2-, grade I-II), Luminal B (ER+, HER2-, grade III), HER2-enriched (HER2+), and triple negative breast cancer (ER/PR-, HER2-). There were 376 breast cancer patients who underwent 464 courses of palliative RT for bone metastases. Radiotherapy included 216 multifraction courses (median dose 20Gy) and 248 single fraction courses (median dose 8Gy). The cohort comprised of: 275 patients with Luminal A, 114 with Luminal B, 46 with HER2-enriched, and 29 with triple negative disease. On multivariate analysis, triple negative breast cancer was associated with a lower rate of partial improvement (OR: 0.37, p = 0.030) and complete improvement (OR: 0.27, p = 0.037). Lower baseline score (OR:1.19, p<0.001) and multiple bone sites treated concurrently (OR: 2.33, p = 0.021) were associated with a higher rate of partial improvement. Use of multifraction RT, chemotherapy, and hormone therapy were not associated with improvement in PRO in the cohort as a whole. In a subgroup analysis of patients with triple negative breast cancer (n = 29), multifraction RT was associated with a higher rate of partial improvement PRO (OR:15.8, p = 0.022) and higher rates of partial and complete improvement in PRO pain-specific scores (OR:19.7, p = 0.012 and OR:12.9, p = 0.035, respectively). Palliative radiotherapy for breast cancer bone metastases was less effective for patients with triple negative disease, even when controlling for the use of systemic therapy and hormone therapy. In this cohort, multifraction radiotherapy was associated with higher rates of symptom relief. There may be a role for dose escalation in this cohort. Otherwise, single fraction radiotherapy was associated with similar rates of symptom relief when compared to multifraction regimens.