Division of Preventive Dentistry, Graduate School of Dentistry, Tohoku University, Sendai, Japan.
Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
PLoS One. 2022 Jun 3;17(6):e0269335. doi: 10.1371/journal.pone.0269335. eCollection 2022.
Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.
We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.
The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010).
Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.
乳腺癌患者的骨转移是医生和牙医共同关注的问题。骨骼相关事件（SREs）的发生会导致骨转移，而骨骼相关事件的发生需要使用骨修饰剂，这种药物会导致颌骨坏死等不良反应。酒精过敏是由于醛脱氢酶-2（ALDH2）活性缺乏引起的不利反应。无活性的 ALDH2 与骨质疏松症有关，但它对骨转移的影响尚不清楚。本研究旨在评估酒精敏感性对原发性可手术乳腺癌患者骨转移和骨骼相关事件的影响。
我们回顾性分析了 2004 年 4 月至 2015 年 9 月期间接受多西紫杉醇（一种抗肿瘤药物）治疗的组织学诊断为乳腺癌的患者。根据对酒精过敏的病历评估酒精敏感性。主要终点是骨转移时间，次要终点是从初始多西紫杉醇治疗开始首次发生骨骼相关事件的时间。数据按酒精敏感性和肿瘤分期分层，差异采用 Kaplan-Meier 法估计。采用多变量 Cox 比例风险模型分析预后危险因素。
酒精高度敏感组（n = 45）的中位随访时间为 54 个月，酒精低度敏感组（n = 287）的中位随访时间为 64 个月。按酒精敏感性分层显示，肿瘤分期与低度敏感患者骨转移的累积发生率显著相关；然而，在高度敏感患者中未发现差异。多变量分析显示，酒精敏感性是骨转移的一个显著预后危险因素（HR 2.721，95% CI 1.268-5.841，P = 0.010）。
酒精敏感性可能是骨转移的一个预后危险因素。需要进行更详细的遗传调查和代谢分析。
