Smith Karen Lisa, Verma Neha, Blackford Amanda L, Lehman Jennifer, Westbrook Kelly, Lim David, Fetting John, Wolff Antonio C, Jelovac Daniela, Miller Robert S, Connolly Roisin, Armstrong Deborah K, Nunes Raquel, Visvanathan Kala, Riley Carol, Papathakis Katie, Zafman Nelli, Sheng Jennifer Y, Snyder Claire, Stearns Vered
Johns Hopkins Women's Malignancies Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
NPJ Breast Cancer. 2022 Apr 21;8(1):53. doi: 10.1038/s41523-022-00414-0.
Many patients discontinue endocrine therapy for breast cancer due to intolerance. Identification of patients at risk for discontinuation is challenging. The minimal important difference (MID) is the smallest change in a score on a patient-reported outcome (PRO) that is clinically significant. We evaluated the association between treatment-emergent symptoms detected by worsening PRO scores in units equal to the MID with discontinuation. We enrolled females with stage 0-III breast cancer initiating endocrine therapy in a prospective cohort. Participants completed PROs at baseline, 3, 6, 12, 24, 36, 48, and 60 months. Measures included PROMIS pain interference, fatigue, depression, anxiety, physical function, and sleep disturbance; Endocrine Subscale of the FACT-ES; and MOS-Sexual Problems (MOS-SP). We evaluated associations between continuous PRO scores in units corresponding to MIDs (PROMIS: 4-points; FACT-ES: 5-points; MOS-SP: 8-points) with time to endocrine therapy discontinuation using Cox proportional hazards models. Among 321 participants, 140 (43.6%) initiated tamoxifen and 181 (56.4%) initiated aromatase inhibitor (AI). The cumulative probability of discontinuation was 23% (95% CI 18-27%) at 48 months. For every 5- and 4-point worsening in endocrine symptoms and sleep disturbance respectively, participants were 13 and 14% more likely to discontinue endocrine therapy respectively (endocrine symptoms HR 1.13, 95% CI 1.02-1.25, p = 0.02; sleep disturbance HR 1.14, 95% CI 1.01-1.29, p = 0.03). AI treatment was associated with greater likelihood of discontinuation than tamoxifen. Treatment-emergent endocrine symptoms and sleep disturbance are associated with endocrine therapy discontinuation. Monitoring for worsening scores meeting or exceeding the MID on PROs may identify patients at risk for discontinuation.
许多患者因不耐受而中断乳腺癌内分泌治疗。识别有中断治疗风险的患者具有挑战性。最小重要差异（MID）是患者报告结局（PRO）评分中具有临床意义的最小变化。我们评估了以等于MID的单位衡量的PRO评分恶化所检测到的治疗中出现的症状与中断治疗之间的关联。我们纳入了0-III期乳腺癌女性患者，前瞻性队列中开始内分泌治疗。参与者在基线、3、6、12、24、36、48和60个月时完成PRO评估。测量指标包括PROMIS疼痛干扰、疲劳、抑郁、焦虑、身体功能和睡眠障碍；FACT-ES内分泌子量表；以及MOS-性问题（MOS-SP）。我们使用Cox比例风险模型评估了与MID相对应单位的连续PRO评分（PROMIS：4分；FACT-ES：5分；MOS-SP：8分）与内分泌治疗中断时间之间的关联。在321名参与者中，140名（43.6%）开始使用他莫昔芬，181名（56.4%）开始使用芳香化酶抑制剂（AI）。48个月时中断治疗的累积概率为23%（95%CI 18-27%）。内分泌症状和睡眠障碍分别每恶化5分和4分，参与者中断内分泌治疗的可能性分别增加13%和14%（内分泌症状HR 1.13，95%CI 1.02-1.25，p = 0.02；睡眠障碍HR 1.14，95%CI 1.01-1.29，p = 0.03）。与他莫昔芬相比，AI治疗中断的可能性更大。治疗中出现的内分泌症状和睡眠障碍与内分泌治疗中断有关。监测PRO评分恶化达到或超过MID可能识别出有中断治疗风险的患者。
