Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, IL, USA.
Lancet Oncol. 2010 Jan;11(1):55-65. doi: 10.1016/S1470-2045(09)70314-6. Epub 2009 Dec 10.
BACKGROUND: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. METHODS: The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. FINDINGS: There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0.97; HR 1.02, 0.54-1.93), but an improvement in disease-free survival for those with a high recurrence score (score > or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. INTERPRETATION: The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes. FUNDING: National Cancer Institute and Genomic Health.
背景：21 基因复发评分检测可预测接受他莫昔芬治疗的淋巴结阴性、雌激素受体阳性乳腺癌患者的预后。低复发评分预示着化疗获益较小。对于淋巴结阳性的乳腺癌，我们研究了在接受他莫昔芬单独治疗的患者中，复发评分是否具有预后意义，以及它是否可以识别出那些尽管复发风险较高，但可能无法从基于蒽环类药物的化疗中获益的患者。
方法：SWOG-8814 期试验是为绝经后淋巴结阳性、雌激素受体阳性乳腺癌患者进行的，结果表明，在他莫昔芬治疗前使用环磷酰胺、多柔比星和氟尿嘧啶（CAF）化疗（CAF-T）可使接受他莫昔芬单独治疗的患者的生存获益。选择肿瘤银行提供标本，通过 RT-PCR 测定复发评分。在这项回顾性分析中，我们使用 Cox 回归分析，按治疗组（他莫昔芬 vs CAF-T）评估复发评分对无病生存的影响，调整阳性淋巴结的数量。
结果：共有 367 份（他莫昔芬组和 CAF-T 组 927 例患者的 40%）标本有足够的 RNA 进行分析（他莫昔芬组 148 例，CAF-T 组 219 例）。在他莫昔芬单独治疗组，复发评分具有预后意义（p=0.006；风险比 [HR] 2.64，95%CI 1.33-5.27，复发评分相差 50 分）。在低复发评分（评分<18；log-rank p=0.97；HR 1.02，0.54-1.93）患者中，CAF 无获益，但在高复发评分（评分≥31；log-rank p=0.033；HR 0.59，0.35-1.01）患者中，无病生存得到改善，校正阳性淋巴结数量后。在治疗组间的复发评分交互作用在最初的 5 年内有统计学意义（p=0.029），但在 5 年后无额外预测（p=0.58），尽管 10 年后仍有累积获益。对于总生存和乳腺癌特异性生存，结果相似。
结论：复发评分可预测淋巴结阳性且接受他莫昔芬治疗的患者的预后，并且可以预测高复发评分肿瘤中 CAF 的显著获益。低复发评分可以识别出那些尽管存在阳性淋巴结，但可能无法从基于蒽环类药物的化疗中获益的女性。
资金来源：美国国立癌症研究所和基因组健康公司。
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