Background: Standard treatment for patients with early-stage estrogen receptor-positive (ER+) breast cancer often includes sequential adjuvant radiation and endocrine therapies. Unfortunately, ~1/3 of patients eventually experience disease recurrence, partly due to residual disease in the form of drug-tolerant persister cancer cells. The anti-cancer efficacy of radiation therapy is partly attributable to the production of oxyradicals that damage biomolecules. We previously showed that endocrine therapy increases mitochondrial content in ER+ breast cancer cells; we postulated that this may also increase oxidative stress. Methods: Herein, we tested the efficacy of concurrent endocrine and radiation therapies, including both conventional (CDR) and ultra-high dose rate (UHDR) radiation. Results: We found that estrogen deprivation and radiation inhibit cell growth, induce apoptosis, and force cells into an oxidatively stressed state. DNA damage was almost exclusive to cells treated with the combination of endocrine and radiation therapy. Radiation slowed tumor growth in two xenograft models, and combination with estrogen deprivation prolonged the time to regrowth in ZR75-1 tumors. Conclusions: These findings indicate that simultaneous treatment with endocrine and radiation therapies can be advantageous, warranting further evaluation to identify tumor features predictive of response to individual and combination treatments.
背景：早期雌激素受体阳性（ER+）乳腺癌患者的标准治疗通常包括序贯辅助放疗和内分泌治疗。遗憾的是，约三分之一患者最终出现疾病复发，部分原因在于存在以药物耐受性持续存在癌细胞形式残留的病灶。放疗的抗癌效果部分归因于其产生的氧自由基对生物分子的损伤作用。我们先前研究发现，内分泌治疗会增加ER+乳腺癌细胞的线粒体含量；我们推测这可能同时加剧氧化应激。方法：本研究评估了内分泌治疗与放疗（包括常规剂量率放疗和超高剂量率放疗）联合应用的疗效。结果：我们发现，雌激素剥夺与放疗均能抑制细胞生长、诱导细胞凋亡，并使细胞处于氧化应激状态。DNA损伤几乎仅见于内分泌与放疗联合治疗的细胞。在两种异种移植模型中，放疗均延缓了肿瘤生长，且联合雌激素剥夺治疗延长了ZR75-1肿瘤的再生时间。结论：这些发现表明内分泌与放疗同步治疗具有协同优势，值得进一步评估以确定可预测单一疗法及联合疗法疗效的肿瘤特征。
Combined Radiation and Endocrine Therapies Elicit Benefit in ER+ Breast Cancer
肿瘤(癌症)患者之家