无论年龄大小，高风险早期乳腺癌女性对术后辅助化疗都可获益。不过，老年女性与年轻女性相比，早期乳腺癌化疗毒性反应较大，化疗方案常常由于毒副作用而复杂化，并且化疗相对剂量强度通常低于预期，导致用药减少和延误，这使肿瘤医师很难按照以治愈为目标的最佳治疗推荐意见将相对剂量强度维持于≥85%。了解哪些女性面临接受次优相对剂量强度的风险，可能为治疗方案讨论提供信息，并指导早期、有针对性的支持护理或老年病共同管理干预措施。 2022年12月1日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国希望之城医疗中心、杜克大学医学院、耶鲁大学医学院、纽约纪念医院斯隆凯特林癌症中心、维克森林大学医学院、内布拉斯加医疗中心、福克斯蔡斯癌症中心、哈佛大学达纳法伯癌症研究院、麻省总医院、罗斯威尔帕克综合癌症中心、芝加哥大学、布朗大学、西德尼金梅尔癌症中心、柯克兰晚期癌症研究组织、华盛顿大学、罗切斯特大学医学中心、北卡罗来纳大学莱恩伯格综合癌症中心的HOPE研究预设二次分析报告，分析了相对剂量强度低于85%的发生率、相关风险因素、对早期乳腺癌老年患者生存结局的影响。HOPE (NCT01472094): The Hurria Older PatiEnts with Breast Cancer Cohort Study (Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults) 该多中心前瞻队列观察研究于2011年9月～2017年5月从全国16家医院入组年龄≥65岁早期乳腺癌术前新辅助或术后辅助化疗女性322例，乳腺癌诊断时中位年龄70岁，范围65～86岁。根据实际与计划化疗剂量强度之比计算相对剂量强度。主要结局指标为相对剂量强度低于85%。通过逐步选择多因素逻辑回归模型，分析基线因素（人口统计学、临床和老年病评分）对相对剂量强度低于85%的影响。通过生存时间曲线推算生存率，并通过对数秩检验对总生存进行比较。 结果，中位随访4年，其中66例（21%）相对剂量强度低于85%。- 年龄≥76岁（比值比：2.57，95%置信区间：1.12～5.91，P=0.03）
- 体力评分较低（比值比：4.32，95%置信区间：1.98～9.42，P<0.001）
- 蒽环类或环磷酰胺、甲氨蝶呤和氟尿嘧啶方案（比值比：3.47，95%置信区间：1.71～7.05，P<0.001）
相对剂量强度<85和≥85%的患者相比，5年总生存率为0.80比0.91，总死亡风险高2.36倍（95%置信区间：1.14～4.87，对数秩P=0.02），对乳腺癌类型进行校正后，总死亡风险高2.47倍（95%置信区间：1.20～5.10，P=0.01）。 因此，该研究结果表明，临床医师通常用较低阈值降低老年患者化疗剂量强度以降低严重毒性反应风险，超过五分之一的老年早期乳腺癌患者接受术后标准化疗相对剂量强度较低，但是较低剂量可能降低治疗效果，导致生存结局较差。开始化疗之前，应该确定并预判最有可能需要减少剂量的老年患者，选择继续化疗的患者可以主动接受额外支持治疗。J Clin Oncol. 2022 Dec 1. IF: 50.717Low-Intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial.Sedrak MS, Sun CL, Ji J, Cohen HJ, Gross CP, Tew WP, Klepin HD, Wildes TM, Dotan E, Freedman RA, O'Connor T, Chow S, Fenton MA, Moy B, Chapman AE, Dale W, Katheria V, Kuderer NM, Lyman GH, Magnuson A, Muss HB.City of Hope, Duarte, CA; Duke University School of Medicine, Durham, NC; Yale School of Medicine, New Haven, CT; Memorial Sloan Kettering Cancer Center, New York, NY; Wake Forest School of Medicine, Winston-Salem, NC; Nebraska Medicine, Omaha, NE; Fox Chase Cancer Center, Philadelphia, PA; Dana-Farber Cancer Institute, Boston, MA; Roswell Park Comprehensive Cancer Center, Buffalo, NY; University of Chicago, Chicago, IL; Brown University, Providence, RI; Massachusetts General Hospital, Boston, MA; Sidney Kimmel Cancer Center/Jefferson Health, Philadelphia, PA; Advanced Cancer Research Group, Kirkland, WA; University of Washington, Seattle, WA; University of Rochester Medical Center, Rochester, NY; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.PURPOSE: Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions.METHODS: This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival.RESULTS: Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; P = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; P < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; P < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank P = .02).CONCLUSION: One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.KEY OBJECTIVE: Women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, irrespective of age. However, compared with younger women, older women with EBC experience increased chemotoxicity and often receive lower than intended relative dose intensity (low RDI) of chemotherapy. Our key objective was to evaluate the incidence of low RDI, the risk factors associated with low RDI, and the relationship between low RDI and survival outcomes in older adults with EBC.KNOWLEDGE GENERATED: In this secondary analysis of a prospective cohort, one in five older women with EBC treated with standard chemotherapy received low RDI and had inferior overall survival.RELEVANCE: Clinicians often have a lower threshold to reduce chemotherapy dose intensity in older patients to reduce the risk of serious toxicity, but lower doses may reduce the efficacy of treatment. This study identifies patients most likely to require dose reductions, so patients who chose to proceed with chemotherapy can receive additional supportive care proactively.DOI: 10.1200/JCO.22.01440
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