Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
Lancet Oncol. 2012 Apr;13(4):420-32. doi: 10.1016/S1470-2045(11)70328-X. Epub 2012 Jan 20.
Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2-3 years of tamoxifen.
In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2-3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome. The relation between musculoskeletal symptoms reported by 6 months from randomisation and survival from 9 months onwards was assessed by Cox proportional hazards models. The trial is registered, number ISRCTN11883920. It has completed accrual and follow-up is continuing for enrolled participants.
After a median follow-up of 91·0 months (IQR 83·0-99·2), carpal tunnel syndrome had been reported for 66 (2·8%) of 2319 patients in the exemestane group compared with 13 (0·6%) of 2338 in the tamoxifen group (odds ratio [OR] 5·23, 99% CI 2·39-11·49; p<0·0001). More events occurred during treatment in the exemestane group than in the tamoxifen group (66 [2·8%] vs seven [0·3%], adjusted OR 9·90, 99% CI 3·52-27·82; p<0·0001). There was no significant difference between groups in events in the post-treatment period (ten with exemestane [0·4%] vs seven with tamoxifen [0·3%]; p=0·46). More patients in the exemestane group (1082 of 2319 patients, 46·7%) had musculoskeletal symptoms than in the tamoxifen group (901 of 2338, 38·5%; OR 1·48, 99% CI 1·32-1·67, p<0·0001). More events occurred during treatment in the exemestane group than in the tamoxifen group (984 [42·4%] vs 776 [33·2%], adjusted OR 1·59, 99% CI 1·32-1·91; p<0·0001), with this difference persisting to some extent in the post-treatment period (449 [19·4%] vs 390 [16·7%]; p=0·017). Of 73 on-treatment cases of carpal tunnel syndrome, 58 (79·5%) completed questionnaires were available. 27 patients (46·6%) had bilateral carpal tunnel syndrome and 31 (53·4%) had unilateral disease; 40 (69·0%) underwent surgical release. The disorder greatly affected daily-life activities in 21 (36·2%) cases. Occurrence of musculoskeletal symptoms, including carpal tunnel syndrome, was associated with improved disease-free survival in unadjusted analysis (p=0·023), but not with overall survival (p=0·36). However, after adjustment for possible confounding factors, musculoskeletal symptoms were not associated with disease-free survival (hazard ratio [HR] 0·96, 95% CI 0·82-1·14, p=0·67) or overall survival (HR 1·02, 95% CI 0·84-1·25, p=0·82).
Occurrence of carpal tunnel syndrome is higher in patients with breast cancer given exemestane than in those treated with tamoxifen, and surgical release might be necessary in most cases. Development of musculoskeletal symptoms in the first 6 months of treatment is not an independent biomarker of improved disease outcome. Further investigation is warranted into the relation between treatment-emergent musculoskeletal symptoms and clinical outcome in patients with breast cancer receiving hormonal therapy.
Pfizer.
与他莫昔芬相比，芳香化酶抑制剂在预防乳腺癌复发方面更有效，但会增加肌肉骨骼方面的副作用，如腕管综合征。本研究旨在评估甾体芳香化酶抑制剂依西美坦或他莫昔芬治疗 2-3 年后接受依西美坦治疗的患者肌肉骨骼症状的危险因素和预后价值。
在国际乳腺癌研究组依西美坦研究中，2-3 年他莫昔芬治疗后无病且仍在治疗的绝经后妇女被随机分配至依西美坦或继续接受他莫昔芬治疗，以完成 5 年内分泌治疗。本回顾性分析的主要终点是发生腕管综合征和任何肌肉骨骼事件，安全性人群包括所有接受任何试验治疗的患者。除病例报告表外，还回顾性地分发了调查问卷，以更详细地了解腕管综合征病例。通过 Cox 比例风险模型评估随机分组后 6 个月时出现的肌肉骨骼症状与 9 个月后生存之间的关系。该试验已完成入组，正在对纳入的参与者进行随访。
中位随访 91.0 个月（IQR 83.0-99.2）后，依西美坦组有 66 例（2.8%）患者报告发生腕管综合征，而他莫昔芬组有 13 例（0.6%）（比值比[OR] 5.23，99%CI 2.39-11.49；p<0.0001）。依西美坦组治疗期间发生的事件多于他莫昔芬组（66 例[2.8%]与 7 例[0.3%]，调整 OR 9.90，99%CI 3.52-27.82；p<0.0001）。两组在治疗后期间的事件发生率无显著差异（依西美坦组 10 例[0.4%]与他莫昔芬组 7 例[0.3%]；p=0.46）。依西美坦组（2319 例患者中有 1082 例，46.7%）的肌肉骨骼症状患者多于他莫昔芬组（2338 例患者中有 901 例，38.5%；OR 1.48，99%CI 1.32-1.67，p<0.0001）。依西美坦组治疗期间发生的事件多于他莫昔芬组（984 例[42.4%]与 776 例[33.2%]，调整 OR 1.59，99%CI 1.32-1.91；p<0.0001），在治疗后期间也存在一定程度的差异（449 例[19.4%]与 390 例[16.7%]；p=0.017）。73 例腕管综合征患者中，58 例（79.5%）完成了调查问卷。27 例（46.6%）患者双侧腕管综合征，31 例（53.4%）单侧疾病；40 例（69.0%）接受手术松解。21 例（36.2%）患者日常生活活动受到严重影响。未经调整分析，肌肉骨骼症状的发生（包括腕管综合征）与无病生存相关（p=0.023），但与总生存无关（p=0.36）。然而，调整可能的混杂因素后，肌肉骨骼症状与无病生存（风险比[HR] 0.96，95%CI 0.82-1.14，p=0.67）或总生存（HR 1.02，95%CI 0.84-1.25，p=0.82）无关。
与接受他莫昔芬治疗的乳腺癌患者相比，接受依西美坦治疗的患者腕管综合征的发生率更高，大多数情况下可能需要手术松解。治疗后 6 个月内出现肌肉骨骼症状不是疾病结局改善的独立生物标志物。需要进一步研究接受激素治疗的乳腺癌患者中治疗后出现的肌肉骨骼症状与临床结局之间的关系。
辉瑞。
