Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco.
Buck Institute for Research on Aging, Novato, California.
JAMA Oncol. 2017 Nov 1;3(11):1503-1510. doi: 10.1001/jamaoncol.2017.1261.
The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment.
To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades.
DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration-cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990.
After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none.
Breast cancer-specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status.
In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors "not ultralow risk," tumor size greater than 2 cm was the most predictive of outcome.
The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.
随着筛查的开展，具有惰性行为的癌症的频率有所增加。需要更好的工具来识别惰性肿瘤，以避免过度治疗。
确定多基因分类器是否与接受 20 年随访的女性浸润性乳腺癌的惰性行为相关。
设计、设置和参与者：这是一项关于他莫昔芬与无全身治疗的随机临床试验的二次分析，随访时间超过 20 年。美国食品和药物管理局批准的 MammaPrint 70 基因表达评分的惰性阈值（超低风险）确定为 15 年内无系统治疗后不会发生乳腺癌死亡。从福尔马林固定石蜡包埋的原发性肿瘤块中进行了免疫组织化学标记物（n=727 名女性）和安捷伦微阵列（n=652 名女性）以进行 MammaPrint 风险评分。参与者为绝经后患有临床检测到的淋巴结阴性乳腺癌的女性，接受乳房切除术或乳房肿块切除术和放射治疗，参加了 1976 年至 1990 年的斯德哥尔摩他莫昔芬（STO-3）试验。
在接受 2 年的他莫昔芬与无全身治疗后，无论激素受体状态如何，无复发且同意的患者进一步随机分配接受 3 年或无额外治疗。
通过 Kaplan-Meier 分析和多变量 Cox 比例风险建模评估乳腺癌特异性生存，调整治疗、患者年龄、诊断年份、肿瘤大小、分级、激素受体以及 ERBB2/HER2 和 Ki67 状态。
在这项针对绝经后淋巴结阴性女性的二次分析中，在进行乳房 X 线筛查之前的时代进行，在可进行 MammaPrint 评分的 652 名女性中（中位年龄为 62.8 岁），377 名（58%）和 275 名（42%）分别为 MammaPrint 低风险和高风险，而 98 名（15%）为超低风险。20 年时，通过 Cox 分析，与超低风险患者相比，70 基因高肿瘤和低肿瘤但非超低风险肿瘤的女性疾病特异性死亡风险显著更高（风险比，4.73[95%CI，1.38-16.22]和 4.54[95%CI，1.40-14.80]）。在 15 年内，超低风险的他莫昔芬治疗组无死亡，这些患者的 20 年疾病特异性生存率为 97%，而未接受治疗的患者的生存率为 94%。递归分区确定超低风险是良好预后的最显著预测因素。在“非超低风险”肿瘤中，肿瘤大小大于 2 cm 是预测结局最具预测性的因素。
70 基因 MammaPrint 检测的超低风险阈值可以识别出手术后单独接受长期全身乳腺癌死亡风险极低的患者。
