Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone
Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone
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DOI：
10.1093/annonc/mdt494
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发表时间：
2014-02-01
影响因子：
50.5
通讯作者：
Nielsen, T. O.
中科院分区：
文献类型：
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作者：
Gnant, M.;Filipits, M.;Nielsen, T. O.
我们证明，在大型临床试验ABCSG-08中，PAM50复发风险评分比标准临床变量提供了远端复发的额外预后信息。这种分子分析已经优化，以确定内在乳腺癌亚型。这些附加的预后信息应该有助于医生决定哪些患者可以不进行辅助化疗。PAM50是一项50个基因的检测，旨在识别内在乳腺癌亚型并产生复发风险（ROR）评分。它已发展到在合格的常规医院病理实验室进行。来自前瞻性随机ABCSG-8试验的1478名绝经后雌激素受体(ER)+早期乳腺癌（EBC）患者接受他莫昔芬或他莫昔芬加阿那曲唑治疗。患者未接受辅助化疗。从石蜡块中提取RNA，用PAM50检测分析。计算内禀亚型（腔内A/B、her2富集、基底样）和ROR评分。初步分析旨在检验连续ROR评分在预测远处复发（DR）方面是否比标准临床变量更有预后价值。在所有测试的亚组中，ROR评分显著增加了临床预测因子的预后信息（P < 0.0001）。PAM50为所有病例分配了一个固有亚型，与luminal B相比，luminal A队列10年的ROR显著降低（P < 0.0001）。在所有测试的亚组中，低危组和高危组之间也存在显著的和临床相关的歧视。初步分析的结果，结合最近发表的ATAC试验的结果，构成了PAM50测试预测ER+ EBC绝经后妇女DR风险的临床有效性的一级证据。在ROR低类别中，10年转移风险< 3.5%，这意味着额外的化疗不太可能改善这一结果——这一发现有助于避免不必要的过度治疗。
We demonstrate that the PAM50 risk of recurrence score provides additional prognostic information for distant recurrences over standard clinical variables in the large clinical trial ABCSG-08. This molecular assay has been optimized to identify intrinsic breast cancer subtypes. This added prognostic information should aid physicians in determining who can be spared adjuvant chemotherapy.PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories.One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables.In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P < 0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P < 0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups.The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of < 3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment.