癌症治疗的后遗症可能增加全身炎症，并表现为合并症和功能减退的风险增加，导致过早死亡。既往缺乏与无癌症同龄配对者自然衰老趋势进行比较的研究。
2016年11月28日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国癌症学会、俄亥俄州立大学的纵向研究报告，调查了乳腺癌生存者和非癌症对照者随着时间推移的促炎细胞因子变化与合并症发生情况。
315位女性（209例乳腺癌和106位对照者）在进行乳腺癌相关检查时入组，完成基线问卷、面谈、采血检测（白细胞介素[IL]-6、IL-1β、肿瘤坏死因子[TNF]-α的脂多糖[LPS]刺激产物）。原发癌症治疗（癌症生存者）或相似时间范围（对照者）6、18个月后重复问卷、面谈、采血检测。生存者和对照者之间的合并症或细胞因子无基线差异。
结果发现，随着时间推移，乳腺癌生存者与对照者相比，TNF-α和IL-6显著较高。与对照者相比，通过手术、放疗、化疗治疗的生存者，在癌症治疗后积累了显著较多的合并症负担、炎症相关疼痛。
该研究的局限性在于：并非设计用于检测衰老加速本身，未检测其他生物学衰老机制（如端粒长度）；参与者在治疗后未观察超过18个月以确定合并症和细胞因子的长期趋势；对照者均在进行乳腺癌相关检查时入组，并且可能不代表无乳腺癌病史的所有女性；样本量不足以调查细胞因子，合并症和疼痛在不同化疗方案、放疗剂量、手术因素、治疗所致绝经、体力活动、体重指数或其他可能造成癌症生存者这些问题因素的差异。
因此，作者认为乳腺癌生存者经过多种治疗后的炎性细胞因子较高、合并症较多，提示衰老加速的可能性。合并症与该样本人群中的炎症相关，这可能增加过早死亡的可能性。由于许多合并症需要多年后发生，未来研究延长随访超过18个月是必要的，以检验癌症生存者衰老加速老化的证据，并确定相应机理。
这些结果强调了乳腺癌生存保健的必要性，包括筛查和治疗合并症、锻炼、饮食和体重管理方案建议，以防止合并症发生，如新公布的美国癌症学会和美国临床肿瘤学会乳腺癌生存保健指南。对于使用多种疗法和选择性雌激素受体调节剂（SERM）治疗的女性，监测尤其重要。
J Clin Oncol. 2016 Nov 28. [Epub ahead of print]
Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?
Alfano CM, Peng J, Andridge RR, Lindgren ME, Povoski SP, Lipari AM, Agnese DM, Farrar WB, Yee LD, Carson WE 3rd, Kiecolt-Glaser JK.
American Cancer Society, Washington, DC; The Ohio State University College of Medicine; The Ohio State University College of Public Health; The Ohio State University, Columbus, OH.
Purpose: The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group.
Methods: Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group).
Results: There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group.
Conclusion: Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.
Supported by National Institutes of Health Grants CA131029, UL1TR000090, CA016058, and K05 CA172296.
PMID: 27893337
DOI: 10.1200/JCO.2016.67.1883
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