Division of Cancer Medicine, Department of Oncology, Oslo University Hospital, Postbox 4953 Nydalen, 0424, Oslo, Norway.
Division of Laboratory Medicine, Department of Pathology, Oslo University Hospital, Oslo, Norway.
Breast Cancer Res. 2017 Nov 14;19(1):120. doi: 10.1186/s13058-017-0911-9.
The aim of this study was to investigate the prognostic value of the PAM50 intrinsic subtypes and risk of recurrence (ROR) score in patients with early breast cancer and long-term follow-up. A special focus was placed on hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) pN0 patients not treated with chemotherapy.
Patients with early breast cancer (n = 653) enrolled in the observational Oslo1 study (1995-1998) were followed for distant recurrence and breast cancer death. Clinicopathological parameters were collected from hospital records. The primary tumors were analyzed using the Prosigna® PAM50 assay to determine the prognostic value of the intrinsic subtypes and ROR score in comparison with pathological characteristics. The primary endpoints were distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS).
Of 653 tumors, 52.2% were classified as luminal A, 26.5% as luminal B, 10.6% as HER2-enriched, and 10.7% as basal-like. Among the HR+/HER2- patients (n = 476), 37.8% were categorized as low risk by ROR score, 22.7% as intermediate risk, and 39.5% as high risk. Median follow-up durations for BCSS and DDFS were 16.6 and 7.1 years, respectively. Multivariate analysis showed that intrinsic subtypes (all patients) and ROR risk classification (HR+/HER2- patients) yielded strong prognostic information. Among the HR+/HER2- pN0 patients with no adjuvant treatment (n = 231), 53.7% of patients had a low ROR, and their prognosis at 15 years was excellent (15-year BCSS 96.3%). Patients with intermediate risk had reduced survival compared with those with low risk (p = 0.005). In contrast, no difference in survival between the low- and intermediate-risk groups was seen for HR+/HER2- pN0 patients who received tamoxifen only. Ki-67 protein, grade, and ROR score were analyzed in the unselected, untreated pT1pN0 HR+/HER2- population (n = 171). In multivariate analysis, ROR score outperformed both Ki-67 and grade. Furthermore, 55% of patients who according to the PREDICT tool ( http://www.predict.nhs.uk/ ) would be considered chemotherapy candidates were ROR low risk (33%) or luminal A ROR intermediate risk (22%).
The PAM50 intrinsic subtype classification and ROR score improve classification of patients with breast cancer into prognostic groups, allowing for a more precise identification of future recurrence risk and providing an improved basis for adjuvant treatment decisions. Node-negative patients with low ROR scores had an excellent outcome at 15 years even in the absence of adjuvant therapy.
本研究旨在探讨 PAM50 内在亚型和复发风险（ROR）评分在早期乳腺癌患者和长期随访中的预后价值。特别关注未接受化疗的激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）pN0 患者。
纳入了观察性 Oslo1 研究（1995-1998 年）中的 653 例早期乳腺癌患者，随访其远处复发和乳腺癌死亡情况。收集了临床病理参数，并从医院记录中获取。通过 Prosigna® PAM50 检测分析原发性肿瘤，以确定内在亚型和 ROR 评分与病理特征相比的预后价值。主要终点是远处无病生存率（DDFS）和乳腺癌特异性生存率（BCSS）。
在 653 例肿瘤中，52.2%为 luminal A 型，26.5%为 luminal B 型，10.6%为 HER2 富集型，10.7%为基底样型。在 HR+/HER2-患者（n=476）中，37.8%的患者根据 ROR 评分被归类为低风险，22.7%为中风险，39.5%为高风险。BCSS 和 DDFS 的中位随访时间分别为 16.6 年和 7.1 年。多变量分析显示，内在亚型（所有患者）和 ROR 风险分类（HR+/HER2-患者）提供了强有力的预后信息。在未接受辅助治疗的 HR+/HER2-pN0 患者（n=231）中，53.7%的患者 ROR 低，其 15 年预后极佳（15 年 BCSS 为 96.3%）。与低风险组相比，中风险组的生存情况较差（p=0.005）。然而，对于仅接受他莫昔芬治疗的 HR+/HER2-pN0 患者，低风险组和中风险组之间的生存差异无统计学意义。Ki-67 蛋白、分级和 ROR 评分在未选择、未经治疗的 pT1pN0 HR+/HER2-人群（n=171）中进行了分析。多变量分析显示，ROR 评分优于 Ki-67 和分级。此外，根据 PREDICT 工具（http://www.predict.nhs.uk/），55%被认为是化疗候选者的患者为 ROR 低风险（33%）或 luminal A ROR 中风险（22%）。
PAM50 内在亚型分类和 ROR 评分可改善乳腺癌患者的预后分组，更准确地识别未来的复发风险，并为辅助治疗决策提供更好的依据。即使没有辅助治疗，ROR 评分低的淋巴结阴性患者在 15 年内仍有极好的预后。
