編者按：根據(jù)與乳腺癌相關的50個基因表達譜（PAM50）對復發(fā)風險進行評分，已被隨機臨床研究證實可以預測10年遠處復發(fā)，但是對于“真實世界”的預測效果尚不明確。

　　2018年1月25日，美國臨床腫瘤學會《臨床腫瘤學雜志》在線發(fā)表丹麥哥本哈根大學、南丹麥大學、美國西雅圖納米串技術公司、加拿大不列顛哥倫比亞大學的“真實世界”研究報告，對PAM50復發(fā)風險評分預測丹麥全國絕經(jīng)后女性隊列激素受體陽性早期乳腺癌單用5年內(nèi)分泌治療的10年遠處復發(fā)進行了驗證。

　　該人群隊列研究通過丹麥乳腺癌協(xié)作組數(shù)據(jù)庫收集了2000年1月～2003年12月丹麥全國絕經(jīng)后女性被診斷為激素受體陽性早期乳腺癌并根據(jù)全國指南接受5年內(nèi)分泌治療的患者隨訪數(shù)據(jù)，對2740例患者的原發(fā)腫瘤標本進行PAM50檢測，并對其中2558例激素受體陽性且人表皮生長因子受體2（HER2）陰性患者進行統(tǒng)計學分析。通過競爭風險回歸模型確定復發(fā)風險評分對遠處復發(fā)的預后價值。

　　結果，經(jīng)過中位隨訪9.2年：

• 對于1395例淋巴結陽性患者

• 359例（26%）復發(fā)風險評分低的實際10年遠處復發(fā)風險低： 3.5%（95%置信區(qū)間： 1.9%～ 6.1%）

• 648例（46%）復發(fā)風險評分高的實際10年遠處復發(fā)風險高：22.1%（95%置信區(qū)間，18.6%～25.8%）

• 對于1163例淋巴結陰性患者

• 復發(fā)風險評分低的實際10年遠處復發(fā)風險低： 5.0%（95%置信區(qū)間： 2.9%～ 8.0%）

• 復發(fā)風險評分高的實際10年遠處復發(fā)風險高：17.8%（95%置信區(qū)間：14.0%～22.0%）

• 對于2421例管腔型腫瘤
  

•  947例管腔B型腫瘤的實際10年遠處復發(fā)風險高：18.4%（95%置信區(qū)間：15.7%～21.3%）

• 1474例管腔A型腫瘤的實際10年遠處復發(fā)風險低： 7.6%（95%置信區(qū)間： 6.1%～ 9.2%，P<0.001）

　　因此，對于該丹麥全國人群，PAM50復發(fā)風險評分提高了結局預測水平。對于“現(xiàn)實世界”，PAM50能夠可靠確定哪些淋巴結陰性患者和相當比例1～3個淋巴結陽性患者遠處復發(fā)風險較低，不必接受輔助化療。

J Clin Oncol. 2018 Jan 25. [Epub ahead of print]

PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer.

Laenkholm AV, Jensen MB, Eriksen JO, Rasmussen BB, Knoop AS, Buckingham W, Ferree S, Schaper C, Nielsen TO, Haffner T, Kibol T, Moller Talman ML, Bak Jylling AM, Tabor TP, Ejlertsen B.

Zealand University Hospital, Slagelse; Rigshospitalet, Copenhagen; Herlev Hospital, Herlev; Odense University Hospital, Odense; Vejle Hospital, Vejle, Denmark; NanoString Technologies, Seattle, WA; University of British Columbia, Vancouver, British Columbia, Canada.

PURPOSE: The PAM50-based Prosigna risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR). The value of Prosigna for predicting DR was examined in a comprehensive nationwide Danish cohort consisting of postmenopausal women with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone.

PATIENTS AND METHODS: Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were treated with endocrine therapy for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna and, after determination of human epidermal growth factor receptor 2 (HER2) status, data from 2,558 hormone receptor-positive/HER2-negative samples were analyzed, including 1,395 node-positive patients. Fine and Gray models were applied to determine the prognostic value of ROR for DR.

RESULTS: Median follow-up for recurrence was 9.2 years. Twenty-six percent of the node-positive patients were classified as low ROR (n = 359) with a DR risk of 3.5% (95% confidence interval [CI], 1.9% to 6.1%) versus a DR risk of 22.1% (95% CI, 18.6% to 25.8%) at 10 years for patients classified as high ROR (n = 648). Node-negative patients classified as low and high ROR had a risk of DR of 5.0% (95% CI, 2.9% to 8.0%) and 17.8% (95% CI, 14.0% to 22.0%), respectively. Luminal B tumors (n = 947; DR risk, 18.4% [95% CI: 15.7% to 21.3%]) had a significantly worse outcome than luminal A tumors (n = 1,474,;DR risk, 7.6% [95% CI: 6.1% to 9.2%]; P < .001).

CONCLUSION: Prosigna ROR score improved the prediction of outcome in this nationwide Danish population. In a real-world setting, Prosigna can reliably identify node-negative patients and a significant proportion of patients with one to three positive nodes who can be spared treatment with adjuvant chemotherapy.

PMID: 29369732

DOI: 10.1200/JCO.2017.74.6586