Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.
Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.
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DOI：
10.1016/s1470-2045(13)70387-5
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Dowsett M
中科院分区：
文献类型：
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作者：
Sgroi DC;Sestak I;Cuzick J;Zhang Y;Schnabel CA;Schroeder B;Erlander MG;Dunbier A;Sidhu K;Lopez-Knowles E;Goss PE;Dowsett M
超过 50% 的雌激素受体阳性 (ER+) 乳腺癌复发发生在辅助内分泌治疗 5 年后。能够改善针对这些晚期复发的长期辅助内分泌治疗的风险效益的生物标志物将具有临床价值。我们在 ATAC 临床试验中比较了乳腺癌指数 (BCI)、Oncotype DX 复发评分 (RS) 和 IHC4 对 ER+、淋巴结阴性 (N0) 疾病患者早期和晚期复发的预后能力。对来自 ER+ 患者的 1102 个原发肿瘤样本进行 BCI，并评估两个版本（BCI-C（主要）和 BCI-L（次要），基于变量的三次和线性组合）。 RS 和 IHC4 值是先前导出的。评估了早期（<5年）和晚期复发（5-10年）的预后区分。为了评估生物标志物预测超出标准临床病理参数的复发的能力，根据 Cox 比例风险模型计算似然比卡方 (LR-Δχ2)。主要终点是远处复发（DR）。在对 665 名 ER+ N0 患者的初步分析中，分类 BCI-C 显示 10 年内 DR 风险存在显着差异 (P<0·0001)。在二次分析中，BCI-L 被证明是一个更强的预测因子，BCI-L、IHC4 和 RS 对早期 DR 具有显着的预后表现（BCI-L，p<0·0002），而只有 BCI-L 对晚期 DR 具有显着的预后作用（LR-Δχ2：7·97，p=0·0048）。对于 5 年早期 DR 风险，BCI-L 将患者的风险分为 59% (390/665)、25% (166/665) 和 16% (109/665)，其中 1.3% (0.5% – 3.1%)、5.6% (2.9% – 10.5%) 和 18.1% (12.0% – 27.0%)分别为低、中、高风险。对于 10 年晚期 DR 风险，BCI-L 将患者分为 61% (366/596)、25% (146/596) 和 14% (84/596)，其中 3.5% (2.0% – 6.1%)、13.4% (8.5% – 20.8%) 和 13.3% (7.4% – 23.4%)分别为低、中、高。虽然所有三种生物标志物均可预测早期 DR，但 BCI-L 是晚期 DR 风险的唯一重要预测指标。三个 BCI-L 组确定了早期和晚期 DR 的两个风险人群，其中 84% (556/665) 的患者早期 DR 风险较低，而少数人群 (39%, 230/596) 具有晚期 DR 高风险，他们可能受益于延长内分泌或其他治疗。雅芳基金会、美国国立卫生研究院、乳腺癌基金会、国防部乳腺癌研究计划、Susan G. Komen 治愈计划、通过玛丽-琼·米切尔·格林基金会突破乳腺癌、阿斯利康、皇家马斯登国家卫生研究院生物医学研究中心。
Greater than 50% of recurrences in estrogen receptor-positive (ER+) breast cancer occur after 5 years of adjuvant endocrine therapy. Biomarkers capable of improving the risk-benefit of extended adjuvant endocrine therapy for these late recurrences would be clinically valuable. We compared the prognostic ability of the Breast Cancer Index (BCI), Oncotype DX Recurrence Score (RS) and IHC4 for both early and late recurrence among patients with ER+, node negative (N0) disease within the ATAC clinical trial. BCI was performed from 1102 primary tumor samples from ER+ patients and two versions (BCI-C (primary) and BCI-L (secondary), based on cubic and linear combinations of the variables) were evaluated. RS and IHC4 values were previously derived. Prognostic discrimination for early (<5y) and late recurrence (5–10y) was assessed. To evaluate the ability of the biomarkers to predict recurrence beyond standard clinicopathological parameters, the likelihood-ratio chi-square (LR-Δχ2) was calculated from Cox proportional hazards models. The primary endpoint was distant recurrence (DR). In the primary analysis of 665 ER+ N0 patients, categorical BCI-C demonstrated significant differences in risk of DR over 10 years (P<0·0001). In the secondary analysis, BCI-L proved to be a much stronger predictor, and BCI-L, IHC4 and RS had significant prognostic performance for early DR (BCI-L, p<0·0002), while only BCI-L was significant for late DR (LR-Δχ2: 7·97, p=0·0048). For risk of early DR at 5 years, BCI-L classified 59% (390/665), 25% (166/665) and 16% (109/665) of patients with 1.3% (0.5% – 3.1%), 5.6% (2.9% – 10.5%) and 18.1% (12.0% – 27.0%) for low, intermediate and high risk, respectively. For risk of late DR at 10 years, BCI-L classified 61% (366/596), 25% (146/596) and 14% (84/596) of patients with 3.5% (2.0% – 6.1%), 13.4% (8.5% – 20.8%) and 13.3% (7.4% – 23.4%) for low, intermediate and high, respectively. While all three biomarkers predicted for early DR, BCI-L was the only significant prognostic for risk of late DR. The three BCI-L groups identified two risk populations for both early and late DR with 84% (556/665) of patients having low risk for early DR, and a smaller population (39%, 230/596) having high risk for late DR who may benefit from extended endocrine or other therapy. Avon Foundation, National Institutes of Health, Breast Cancer Foundation, DOD Breast Cancer Research Program, Susan G. Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, Astrazeneca, NIHR Biomedical Research Centre at the Royal Marsden.