Roberts Kate E, Rickett Kirsty, Feng Sophie, Vagenas Dimitrios, Woodward Natasha E
Princess Alexandra Hospital, Department of Medical Oncology, Ipswich Road, Woolloongabba, Queensland, Australia.
Mater Hospital, University of Queensland, School of Clinical Medicine, Mater Clinical Unit, South Brisbane, Australia, 4101.
Cochrane Database Syst Rev. 2020 Jan 29;1(1):CD012988. doi: 10.1002/14651858.CD012988.pub2.
BACKGROUND: Survival for stage I to III, hormone receptor-positive, breast cancer has substantially improved over time due to advances in screening, surgery and adjuvant therapy. However many adjuvant therapies have significant treatment-related toxicities, which worsen quality of life for breast cancer survivors. Postmenopausal women with hormone receptor-positive breast cancer are now prescribed aromatase inhibitors (AI) as standard, with longer durations of therapy, up to 10 years, being considered for certain women. AI treatment is associated with a high incidence of AI-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS reduces compliance with AI therapy in up to one half of women undergoing adjuvant AI therapy, potentially compromising breast cancer outcomes. Exercise has been investigated for the prevention and treatment of AIMSS but the effect of this intervention remains unclear. OBJECTIVES: To assess the effects of exercise therapies on the prevention or management of aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) in women with stage I to III hormone receptor-positive breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases up to 13 December 2018. We also searched two conference proceedings portals and two clinical trials registries for ongoing studies or unpublished trials, or both, in August 2019. We also reviewed reference lists of the included studies. SELECTION CRITERIA: We included randomised controlled trials that compared exercise versus a comparator arm. We did not impose any restriction on the comparator arm, which could include an alternative type of exercise, no exercise or a waiting list control. Both published and non-peer-reviewed studies were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed risk of bias and certainty of the evidence using the GRADE approach. The outcomes investigated were pain, joint stiffness, grip strength, health-related quality of life, cancer-specific quality of life, adherence to AI therapy, adverse events, incidence of AIMSS, breast cancer-specific survival and overall survival. For continuous outcomes that were assessed with the same instrument, we used the mean difference (MD); for those outcomes that used different instruments, we used the standardised mean difference (SMD) for the analysis. For dichotomous outcomes, we reported outcomes as an odds ratio (OR). MAIN RESULTS: We included seven studies with 400 randomised participants; one study assessed exercise for preventing AIMSS and six studies assessed treating AIMSS. For preventing AIMSS, the single study reported no difference in pain scores, grip strength or compliance to taking AI medication between groups. Data values were not provided in the study and no other outcomes were reported. For managing AIMSS, we found that the evidence for the effect of exercise therapies on overall change in worst pain scores was very uncertain (SMD -0.23, 95% confidence interval (CI) -0.78 to 0.32; 4 studies, 284 women; very low-certainty evidence). The evidence suggested that exercise therapies result in little to no difference in overall change in stiffness scores (Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) stiffness score MD -0.76, 95% CI -1.67 to 0.15 and Visual Analogues Scale (VAS) stiffness score MD -0.42, 95% CI -2.10 to 1.26; 1 study, 53 women; low-certainty evidence). The evidence was very uncertain for the outcomes of overall change in grip strength (MD 0.30, 95% CI -0.55 to 1.15; 1 study, 83 women; very low-certainty evidence); overall change in health-related quality of life (subscales of SF-36 tool ranged from least benefit of MD 1.88, 95% CI -2.69 to 6.45 to most benefit of MD 9.70, 95% CI 1.67 to 17.73; 2 studies, 123 women, very low-certainty evidence); overall change in cancer-specific quality of life (MD 4.58, 95% CI -0.61 to 9.78; 2 studies, 136 women; very low-certainty evidence); and adherence to aromatase inhibitors (OR 2.43, 95% CI 0.41 to 14.63; 2 studies, 224 women; very low-certainty evidence). There were no adverse events identified across four studies in either arm (0 events reported; 4 studies; 331 participants; low-certainty evidence). There were no data reported on incidence of AIMSS, breast cancer-specific survival or overall survival. AUTHORS' CONCLUSIONS: Given the wide-ranging benefits of exercise for people affected by cancer, it was surprising that this review provided no clear evidence of benefit for exercise therapies in women with early breast cancer with AIMSS. This review only yielded seven eligible studies with 400 participants, which is likely to have underpowered the findings. The meta-analysis was challenging due to the considerable heterogeneity amongst the trials, with a wide range of exercise regimens and follow-up periods. Despite these inconclusive findings, exercise needs to be part of routine care for women with breast cancer due to its wide-ranging benefits. Future research in this area would be enhanced with further understanding of the mechanism of AIMSS, a single clear definition of the condition, and phase III randomised controlled trials that are adequately powered to test targeted exercise interventions on the key clinical outcomes in this condition.
背景:由于筛查、手术及辅助治疗的进展,I至III期激素受体阳性乳腺癌患者的生存率随时间推移有了显著提高。然而,许多辅助治疗存在与治疗相关的严重毒性,这会降低乳腺癌幸存者的生活质量。绝经后激素受体阳性乳腺癌女性患者目前常规使用芳香化酶抑制剂(AI)进行治疗,对于部分患者,考虑采用长达10年的更长疗程治疗。AI治疗与AI诱导的肌肉骨骼症状(AIMSS)高发相关,常表现为关节对称性疼痛和酸痛、肌肉骨骼疼痛及关节僵硬。在接受辅助AI治疗的女性中,高达一半的患者因AIMSS而降低了对AI治疗的依从性,这可能会影响乳腺癌治疗效果。已有研究对运动预防和治疗AIMSS的效果进行了探讨,但该干预措施的效果仍不明确。 目的:评估运动疗法对I至III期激素受体阳性乳腺癌女性患者预防或管理芳香化酶抑制剂诱导的肌肉骨骼症状(AIMSS)的效果。 检索方法:我们检索了截至2018年12月13日的Cochrane乳腺癌专业注册库、CENTRAL、MEDLINE、Embase和CINAHL数据库。2019年8月,我们还检索了两个会议论文平台和两个临床试验注册库,以查找正在进行的研究或未发表的试验,或两者皆查。我们还查阅了纳入研究的参考文献列表。 入选标准:我们纳入了比较运动与对照臂的随机对照试验。我们对对照臂未作任何限制,对照臂可以包括另一种运动类型、不运动或等待名单对照。已发表和未经同行评审的研究均符合入选标准。 数据收集与分析:两位综述作者独立提取数据,使用GRADE方法评估偏倚风险和证据的确定性。所调查的结局包括疼痛、关节僵硬、握力、健康相关生活质量、癌症特异性生活质量、AI治疗的依从性、不良事件、AIMSS发病率、乳腺癌特异性生存率和总生存率。对于使用相同工具评估的连续性结局,我们使用平均差(MD);对于使用不同工具的结局,我们使用标准化平均差(SMD)进行分析。对于二分结局,我们将结局报告为比值比(OR)。 主要结果:我们纳入了7项研究,共400名随机参与者;1项研究评估了运动对预防AIMSS的效果,6项研究评估了运动对治疗AIMSS的效果。对于预防AIMSS,该单项研究报告称,两组之间在疼痛评分、握力或服用AI药物的依从性方面无差异。该研究未提供数据值,也未报告其他结局。对于管理AIMSS,我们发现运动疗法对最严重疼痛评分总体变化的效果证据非常不确定(SMD -0.23,95%置信区间(CI)-0.78至0.32;4项研究,284名女性;极低确定性证据)。证据表明,运动疗法对僵硬评分总体变化的影响很小或无差异(西安大略和麦克马斯特大学骨关节炎指数(WOMAC)僵硬评分MD -0.76,95% CI -1.67至0.15;视觉模拟量表(VAS)僵硬评分MD -0.42,95% CI -2.10至1.26;1项研究,53名女性;低确定性证据)。握力总体变化结局的证据非常不确定(MD 0.30,95% CI -0.55至1.15;1项研究,83名女性;极低确定性证据);健康相关生活质量总体变化(SF-36工具子量表,获益最小为MD 1.88,95% CI -2.69至6.45,获益最大为MD 9.70,95% CI 1.67至17.73;2项研究,123名女性,极低确定性证据);癌症特异性生活质量总体变化(MD 4.58,95% CI -0.61至9.78;2项研究,136名女性;极低确定性证据);以及对芳香化酶抑制剂的依从性(OR 2.43,95% CI 0.41至14.63;2项研究,224名女性;极低确定性证据)。在四项研究中,两组均未发现不良事件(报告0起事件;4项研究;331名参与者;低确定性证据)。未报告关于AIMSS发病率、乳腺癌特异性生存率或总生存率的数据。 作者结论:鉴于运动对癌症患者具有广泛益处,本综述未提供明确证据证明运动疗法对患有AIMSS的早期乳腺癌女性有益,这令人惊讶。本综述仅纳入了7项符合条件的研究,共400名参与者,这可能导致研究结果的检验效能不足。由于试验之间存在相当大的异质性,包括广泛的运动方案和随访期,荟萃分析具有挑战性。尽管结果尚无定论,但鉴于运动具有广泛益处,运动应成为乳腺癌女性常规护理的一部分。未来该领域的研究可通过进一步了解AIMSS的机制、对该病症的单一明确定义以及有足够检验效能来测试针对性运动干预对该病症关键临床结局影响的III期随机对照试验得到加强。
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