A nested cohort study of 6,248 early breast cancer patients treated in neoadjuvant and adjuvant chemotherapy trials investigating the prognostic value of chemotherapy-related toxicities.
A nested cohort study of 6,248 early breast cancer patients treated in neoadjuvant and adjuvant chemotherapy trials investigating the prognostic value of chemotherapy-related toxicities.
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DOI：
10.1186/s12916-015-0547-5
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发表时间：
2015-12-29
期刊：
影响因子：
9.3
通讯作者：
Earl HM
中科院分区：
文献类型：
--
作者：
Abraham JE;Hiller L;Dorling L;Vallier AL;Dunn J;Bowden S;Ingle S;Jones L;Hardy R;Twelves C;Poole CJ;Pharoah PD;Caldas C;Earl HM
化疗相关毒性与预后之间的关系尚不清楚。先前的研究已经检查了骨髓抑制参数或神经病变与生存的关系，并报告了相互矛盾的结果。本研究旨在调查 13 种常见化疗毒性及其与无复发生存率和乳腺癌特异性生存率的关系。通过四项随机对照试验（NEAT；BR9601；tAnGo；Neo-tAnGo）前瞻性收集了 6,248 名早期乳腺癌女性的化疗相关毒性。 Cox比例风险模型用于分析化疗相关毒性与乳腺癌特异性生存率和无复发生存率之间的关联。模型包括重要的预后因素，并按违反比例风险假设的变量进行分层。多变量分析确定严重中性粒细胞减少症（≥3级）是无复发生存的独立预测因子（风险比（HR） = 0.86；95%置信区间（CI），0.76–0.97；P = 0.02）。乳腺癌特异性生存率也存在类似趋势（HR = 0.87；95% CI，0.75–1.01；P = 0.06）。正常/低 BMI 患者比 BMI 较高的患者经历更严重的中性粒细胞减少症 (P = 0.008)。疲劳患者（≥3级）表现出生存率降低的趋势（乳腺癌特异性生存率：HR = 1.17；95% CI，0.99–1.37；P = 0.06）。在按治疗成分进行的 NEAT/BR9601 亚组分析中，这种效果具有统计学意义（HR = 1.61；95% CI，1.13–2.30；P = 0.009）。这项大型研究表明化疗引起的中性粒细胞减少症与生存率增加之间存在显着关联。它还确定了低/正常体重指数与严重中性粒细胞减少症发生率增加之间的密切关系。它为支持中性粒细胞减少症适应临床试验的发展提供了证据，以研究最佳剂量计算及其对临床结果的影响。这对于肥胖可能导致化疗剂量不理想的人群很重要。本文的在线版本 (doi:10.1186/s12916-015-0547-5) 包含补充材料，可供授权用户使用。
The relationship between chemotherapy-related toxicities and prognosis is unclear. Previous studies have examined the association of myelosuppression parameters or neuropathy with survival and reported conflicting results. This study aims to investigate 13 common chemotherapy toxicities and their association with relapse-free survival and breast cancer-specific survival. Chemotherapy-related toxicities were collected prospectively for 6,248 women with early-stage breast cancer from four randomised controlled trials (NEAT; BR9601; tAnGo; Neo-tAnGo). Cox proportional-hazards modelling was used to analyse the association between chemotherapy-related toxicities and both breast cancer-specific survival and relapse-free survival. Models included important prognostic factors and stratified by variables violating the proportional hazards assumption. Multivariable analysis identified severe neutropenia (grades ≥3) as an independent predictor of relapse-free survival (hazard ratio (HR) = 0.86; 95 % confidence interval (CI), 0.76–0.97; P = 0.02). A similar trend was seen for breast cancer-specific survival (HR = 0.87; 95 % CI, 0.75–1.01; P = 0.06). Normal/low BMI patients experienced more severe neutropenia (P = 0.008) than patients with higher BMI. Patients with fatigue (grades ≥3) showed a trend towards reduced survival (breast cancer-specific survival: HR = 1.17; 95 % CI, 0.99–1.37; P = 0.06). In the NEAT/BR9601 sub-group analysis by treatment component, this effect was statistically significant (HR = 1.61; 95 % CI, 1.13–2.30; P = 0.009). This large study shows a significant association between chemotherapy-induced neutropenia and increased survival. It also identifies a strong relationship between low/normal BMI and increased incidence of severe neutropenia. It provides evidence to support the development of neutropenia-adapted clinical trials to investigate optimal dose calculation and its impact on clinical outcome. This is important in populations where obesity may lead to sub-optimal chemotherapy doses. The online version of this article (doi:10.1186/s12916-015-0547-5) contains supplementary material, which is available to authorized users.