哪些乳腺癌女性无法坚持内分泌治疗
内分泌治疗可减少将近50%的乳腺癌复发风险和大约30%的乳腺癌死亡风险。不过,内分泌治疗至少需要5年,调查发现多达50%的女性无法坚持完成5年内分泌治疗,尤其年轻未绝经女性。了解乳腺癌术后内分泌治疗早期停药的可改变风险因素,有助于临床医师早期发现这些患者并及时进行早期干预。
2021年6月17日,《美国医学会杂志》肿瘤学分册在线发表芝加哥西北大学、哈佛大学达纳法伯癌症研究所、爱因斯坦医学院、密歇根大学、埃默里大学、布朗大学、斯坦福大学、维克森林大学、加拿大麦克马斯特大学的TAILORx研究事后分析报告,探讨了乳腺癌术后早期停止内分泌治疗相关可改变风险因素、多重用药以及其他药物(例如抗抑郁药和阿片类)的影响。
TAILORx (NCT00310180): Trial Assigning IndividuaLized Options for TReatment: Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer: Program for the Assessment of Clinical Cancer Tests (PACCT-1)
该事后分析于2020年1月15日~2021年4月6日对2006年4月7日~2010年10月6日参加TAILORx随机对照临床研究的954例激素受体阳性、HER2阴性、腋窝淋巴结阴性乳腺癌术后一年内开始内分泌治疗患者亚组(平均年龄56.6±8.9岁)进行意向治疗人群分析。患者内分泌治疗开始之前完成癌症相关健康生活质量评分,包括生理健康和心理健康。内分泌治疗早期停止的定义为内分泌治疗开始4年内由于非死亡或非复发原因而停药。利用生存曲线分析停药时间与停药率,利用多因素比例风险回归联合预测模型分析内分泌治疗坚持率与患者个人因素的相关性。
结果,根据联合模型分析:
内分泌治疗±化疗相比:早期停药风险低43%(风险比:0.57,95%置信区间:0.35~0.92,P=0.02)
41~50岁与≤40岁相比:早期停药风险低61%(风险比:0.39,95%置信区间:0.18~0.85,P=0.02)
51~60岁与≤40岁相比:早期停药风险低72%(风险比:0.28,95%置信区间:0.13~0.60,P=0.001)
61~70岁与≤40岁相比:早期停药风险低60%(风险比:0.40,95%置信区间:0.18~0.86,P=0.02)
70岁以上与≤40岁相比:早期停药风险低77%(风险比:0.23,95%置信区间:0.07~0.77,P=0.02)
对化疗和年龄进行校正后:
有抑郁史与无抑郁史相比:早期停药风险高82%(风险比:1.82,95%置信区间:1.19~2.77,P=0.005)
生理评分较低与较高相比:早期停药风险高112%(风险比:2.12,95%置信区间:1.30~3.45,P=0.002)
心理评分较低与较高相比:早期停药风险高94%(风险比:1.94,95%置信区间:1.20~3.13,P=0.006)
服用抗抑郁药与未用相比:早期停药风险高87%(风险比:1.87,95%置信区间:1.23~2.84,P=0.003)
因此,该随机对照临床研究事后分析结果表明,除了化疗和年龄等不可改变因素之外,乳腺癌术后内分泌治疗开始前患者报告健康相关生活质量(例如抑郁、生理健康差、心理健康差)是早期停止内分泌治疗的重要风险因素。这些结果支持对患者报告结局和抑郁症状进行系统筛查,有助早期发现有停止内分泌治疗风险的女性进行及时干预。
相关链接
JAMA Oncol. 2021 Jun 17. Online ahead of print.
Association of Modifiable Risk Factors With Early Discontinuation of Adjuvant Endocrine Therapy: A Post Hoc Analysis of a Randomized Clinical Trial.
Yanez B, Gray RJ, Sparano JA, Carlos RC, Sadigh G, Garcia SF, Gareen IF, Whelan TJ, Sledge GW, Cella D, Wagner LI.
Northwestern University Feinberg School of Medicine, Chicago, Illinois; Dana Farber Cancer Institute, Boston, Massachusetts; Albert Einstein College of Medicine, Bronx, New York; University of Michigan Comprehensive Cancer Center, Ann Arbor; Emory University School of Medicine, Atlanta, Georgia; Brown University, Providence, Rhode Island; McMaster University, Hamilton, Ontario, Canada; Stanford Cancer Center Palo Alto, Stanford, California; Wake Forest University Health Sciences, Winston Salem, North Carolina.
This post hoc analysis of a randomized clinical trial examines the association between early discontinuation of endocrine therapy in the TAILORx study and modifiable risk factors, polypharmacy, and types of additional medications.
QUESTION: What risk factors are associated with early discontinuation of endocrine therapies among women with breast cancer in the Trial Assigning Individualized Options for Treatment?
FINDINGS: In this post hoc analysis of a randomized clinical trial, including 954 women with breast cancer, baseline patient-reported health-related quality of life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies.
MEANING: Patient-reported outcomes can identify patients at increased risk for early discontinuation of endocrine therapies and select intervention targets.
IMPORTANCE: Early discontinuation of adjuvant endocrine therapy (ET) is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the recommended full 5 years of ET treatment.
OBJECTIVE: To identify the association between early discontinuation of ET in the Trial Assigning Individualized Options for Treatment (TAILORx) and modifiable risk factors, polypharmacy, and types of additional medications such as antidepressants and opioids.
DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis includes a subgroup of 954 patients with breast cancer in TAILORx, a randomized clinical trial conducted from April 7, 2006, to October 6, 2010. All participants received a diagnosis of hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer and started ET within a year of study entry. Analyses were conducted in the intent-to-treat population. Statistical analysis took place from January 15, 2020, to April 6, 2021.
MAIN OUTCOMES AND MEASURES: Participants completed measures on cancer-related health-related quality of life including physical well-being and social well-being prior to initiating ET. Early discontinuation of ET was defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence. Kaplan-Meier estimates were used to calculate discontinuation, and Cox proportional hazards regression joint prediction models were used to analyze the association between rates of adherence to ET with patient-level factors.
RESULTS: A total of 954 women (mean [SD] age, 56.6 [8.9] years) were included in this analysis. In a joint model, receipt of chemoendocrine therapy (vs receipt of ET only; hazard ratio [HR], 0.57; 95% CI, 0.35-0.92; P = .02) and age older than 40 years (vs ≤40 years; HR for 41-50 years, 0.39; 95% CI, 0.18-0.85; P = .02; HR for 51-60 years, 0.28; 95% CI, 0.13-0.60; P = .001; HR for 61-70 years, 0.40; 95% CI, 0.18-0.86; P = .02; and HR for >70 years, 0.23; 95% CI, 0.07-0.77; P = .02) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared with no history of depression (HR, 1.82; 95% CI, 1.19-2.77; P = .005), worse physical well-being compared with better physical well-being (HR, 2.12; 95% CI, 1.30-3.45; P = .002), and worse social well-being compared with better social well-being (HR, 1.94; 95% CI, 1.20-3.13; P = .006) were individually and significantly associated with a higher probability of early discontinuation of ET. Only antidepressant use at study baseline was associated with early discontinuation (HR, 1.87; 95% CI, 1.23-2.84; P = .003).
CONCLUSIONS AND RELEVANCE: In this post hoc analysis of a randomized clinical trial, baseline patient-reported health-related quality of life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies. These results support systematic screening for patient-reported outcomes and depressive symptoms to identify women at risk for discontinuation of ET.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00310180
PMID: 34137783
DOI: 10.1001/jamaoncol.2021.1693