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编者按：众所周知，瘦弱和肥胖均可增加癌症患者的死亡风险。不过，还有一种特殊情况，即身高、体重、体重指数（体重与身高平方之比）基本正常，看似不胖不瘦，但是肌肉（体积或密度）减少而脂肪增加，形成一种特殊的肌肉减少型肥胖或脂肪过多型瘦弱。既往研究发现肌肉（体积或密度）减少和脂肪过多，与转移性乳腺癌患者的死亡率增加相关，但是与非转移性乳腺癌患者预后的相关性尚不明确。
2018年4月5日，《美国医学会杂志》肿瘤学分册在线发表美国凯泽永久医疗集团、加拿大阿尔伯塔大学、哈佛大学医学院达纳法伯癌症研究所的观察研究报告，通过计算机断层扫描（CT）检测了肌肉和脂肪与非转移性乳腺癌患者生存的相关性。
凯泽永久：美国最大的医疗保险保健保障集团，创立于1945年，总部位于加利福尼亚州奥克兰，业务遍布美国8个州和首都华盛顿哥伦比亚特区，拥有自己的医疗保险基金、医院医生、教学研究机构。截至2017年10月，拥有1170万医疗保险客户、20.8975万员工、2.1275万医生、5.4072万护士、39个医疗中心、720个医疗机构。由于该集团需要为所有医疗保险客户的医疗保障提供全程医疗保健，故其参与研究的样本量和现实意义相当大。
该观察研究从凯泽永久医疗集团（北加利福尼亚地区）和哈佛大学达纳法伯癌症研究院（波士顿地区）入组2000年1月～2013年12月诊断为II或III期乳腺癌女性3241例（年龄18～80岁，中位54岁），根据非转移性乳腺癌诊断时通过CT从临床获得的3种人体组成指标（肌肉体积、肌肉密度、脂肪组织）以及最终死亡率随访结果，计算死亡风险比，以评定全因死亡率与肌肉体积减少、肌肉密度减少、总脂肪组织之间的相关性。并且，通过多因素比例风险回归模型，根据不同的社会人口统计学指标（诊断时年龄、种族）、肿瘤特征（分期、分级、雌激素受体、HER2）、治疗方案（手术、化疗）、体重指数（以体重公斤除以身高平方米计算）以及其他人体组成指标等影响因素，对上述相关性进行校正。此外，还对肌肉减少（是、否）类别和总脂肪组织三分位数与结局的交叉分类进行评定。主要结局衡量指标为总生存时间和全因死亡率。
结果，经过中位随访6.0年，1086例患者（34%）出现肌肉体积减少，1199例患者（37%）出现肌肉密度减少。
通过多因素比例风险回归模型，校正其他影响因素后，对于非转移性乳腺癌患者：
伴有肌肉体积减少与不伴肌肉体积减少的患者相比，总死亡风险增加41%（风险比：1.41，95%置信区间：1.18～1.69）
脂肪组织最高三分之一与最低三分之一的患者相比，总死亡风险增加35%（风险比：1.35，95%置信区间：1.08～1.69）
肌肉体积减少且总脂肪组织增加患者的死亡率最高，总死亡风险增加89%（风险比：1.89，95%置信区间：1.30～2.73）
肌肉密度、体重指数与总死亡率无统计学独立显著相关性
因此，对于非转移性乳腺癌，肌肉（体积或密度）减少被低估，并且发生于三分之一以上的新诊断患者，与无肌肉减少的患者相比，死亡风险显著增加。不过，肌肉密度减少与生存无关，肌肉体积减少且总脂肪组织高的患者死亡率最高。通过CT从临床获得非转移性乳腺癌患者肌肉减少和脂肪过多的测量值，可以提供优于体重指数的显著重要预后信息，并且将有助于确定高风险人群、指导干预以优化生存结局。
对此，新泽西州立罗格斯大学、斯坦福大学医学院、加利福尼亚癌症预防研究院发表特邀评论：肥胖、人体组成与乳腺癌的新兴科学。
JAMA Oncol. 2018 Apr 5. [Epub ahead of print]
Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer.
Caan BJ, Cespedes Feliciano EM, Prado CM, Alexeeff S, Kroenke CH, Bradshaw P, Quesenberry CP, Weltzien EK, Castillo AL, Olobatuyi TA, Chen WY.
Kaiser Permanente, Oakland, California; University of Alberta, Edmonton, Alberta, Canada; Dana Farber Cancer Institute, Boston, Massachusetts.
QUESTION: Are sarcopenia, poor muscle quality, and excess adiposity at diagnosis associated with overall mortality in patients with nonmetastatic breast cancer?
FINDINGS: In this observational study of 3241 patients with breast cancer, more than one-third presented with sarcopenia at diagnosis, and those women had a significantly increased risk of death compared with patients without sarcopenia. Poor muscle quality was not associated with survival, and highest mortality was in patients with sarcopenia and high total adipose tissue.
MEANING: Measures of sarcopenia provide significant prognostic information in nonmetastatic breast cancer and will help to identify high-risk groups and guide interventions to optimize survival outcomes.
IMPORTANCE: Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown.
OBJECTIVE: To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes.
MAIN OUTCOMES AND MEASURES: Overall survival time and all-cause mortality.
RESULTS: Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition.
CONCLUSIONS AND RELEVANCE: Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.
PMID: 29621380
DOI: 10.1001/jamaoncol.2018.0137
JAMA Oncol. 2018 Apr 5. [Epub ahead of print]
Obesity, Body Composition, and Breast Cancer: An Evolving Science.
Bandera EV, John EM.
Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick; Cancer Prevention Institute of California, Stanford University School of Medicine, Fremont.
PMID: 29621383
DOI: 10.1001/jamaoncol.2018.0125
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