BackgroundRecent evidence indicates that a dysregulated host metabolism influences treatment outcomes in patients with breast cancer. We investigated the association of computed tomography (CT)‐derived body composition indices with therapeutic responses in patients with hormone receptor‐positive, HER2‐negative advanced breast cancer (ABC) on endocrine plus CDK4/6 inhibitor (CDK4/6i) treatment.MethodsThe study involved a retrospective cohort of patients with ABC at the Yonsei Cancer Center who received CDK4/6i and aromatase inhibitors as first‐line therapy between January 2017 and October 2020. Body composition parameters were estimated from the non‐enhanced CT images of the third lumbar spine by commercialized deep learning software. Patients with low skeletal muscle radiodensity (SMD) were defined as patients with SMD of low tertile (≤ 28.7 Hounsfield Units). The primary outcome was progression‐free survival (PFS).ResultsAmong the 247 female participants (median age, 53 years; mean body mass index [BMI], 23.7 kg/m2), 45.7% had disease progression or death during a median follow‐up of 36.4 months. After adjusting for age and visceral metastasis, SMD was the only independent predictor among body composition parameters for worse PFS (adjusted hazard ratio [HR] = 1.20 per standard deviation decrement, 95% CI: 1.01–1.42, p = 0.041), whereas BMI, muscle area, and fat area were not. Participants with low SMD had a higher risk of progression than those without (PFS, 27.2 vs. 51.1 months, p = 0.009; adjusted HR 1.84, 95% CI: 1.22–2.76, p = 0.003). Strong associations between low SMD and poor PFS were observed in groups with pre‐menopause status (HR, 3.04 vs. 1.19 in post‐menopause; 95% CI: 1.54–5.99, p for interaction < 0.05) and without visceral metastases (HR, 2.95 vs. 1.19 in with visceral metastases; 95% CI: 1.59–5.49, p for interaction < 0.05).ConclusionsCT‐defined low SMD predicts poor treatment outcomes in patients with ABC undergoing first‐line treatment with aromatase inhibitors and CDK4/6i.

中文翻译：

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低骨骼肌放射密度可预测晚期乳腺癌对 CDK4/6 抑制剂加芳香化酶抑制剂的反应


背景最近的证据表明，失调的宿主代谢会影响乳腺癌患者的治疗结果。我们研究了内分泌加 CDK4/6 抑制剂 （CDK4/6i） 治疗后激素受体阳性、HER2 阴性晚期乳腺癌 （ABC） 患者计算机断层扫描 （CT） 衍生的体成分指标与治疗反应的相关性。方法该研究涉及延世癌症中心的 ABC 患者回顾性队列，这些患者在 2017 年 1 月至 2020 年 10 月期间接受 CDK4/6i 和芳香化酶抑制剂作为一线治疗。通过商业化的深度学习软件从第三腰椎的非增强 CT 图像中估计身体成分参数。骨骼肌放射密度 （SMD） 低的患者定义为低三分位数 （≤ 28.7 Hounsfield 单位） 的 SMD 患者。主要结局是无进展生存期 （PFS）。结果在 247 名女性参与者 （中位年龄 53 岁;平均体重指数 [BMI] ，23.7 kg/m2） 中，45.7% 的患者在中位随访 36.4 个月期间出现疾病进展或死亡。在调整了年龄和内脏转移后，SMD 是 PFS 较差的体成分参数中唯一的独立预测因子 （调整后的风险比 [HR] = 1.20每个标准差递减，95% CI：1.01-1.42，p = 0.041），而 BMI、肌肉面积和脂肪面积则不是。低 SMD 参与者的进展风险高于无 SMD 的参与者（PFS，27.2 vs. 51.1 个月，p = 0.009;调整后 HR 1.84,95% CI：1.22-2.76，p = 0.003）。在绝经前状态的组中观察到低 SMD 和差 PFS 之间的强烈关联 （HR，3.04 vs. 绝经后 1.19;95% CI：1.54-5.99，交互作用 < 0.05）和无内脏转移 （HR，2.95 vs. 1.19 英寸有内脏转移;95% CI：1.59–5.49，交互作用 < 的 p 为 0.05）。结论CT 定义的低 SMD 预示着接受芳香化酶抑制剂和 CDK4/6i 一线治疗的 ABC 患者的治疗结局不佳。