1990至2009年间入组临床试验的早期乳腺癌女性复发率下降：151项试验中155,746名女性的联合分析

ER阳性早期乳腺癌女性的远处复发在诊断后超过20年仍以恒定速率持续发生，而ER阴性乳腺癌的类似数据则较少。利用早期乳腺癌试验协作组（EBCTCG）数据库，我们调查了ER阳性与ER阴性肿瘤的远处复发率及其随时间的变化。在此联合分析中，筛选了EBCTCG数据库中超过65万名早期乳腺癌患者的随机对照试验数据。患者符合条件者为1990年至2009年间登记的、首次诊断为ER阳性且计划接受至少5年内分泌治疗的患者，或ER阴性患者，且诊断时年龄未满75岁，肿瘤直径≤50 mm，腋窝淋巴结阳性数少于10个，无远处转移证据。排除接受新辅助治疗、辅助治疗不明确、ER阴性但PR阳性或缺乏结局或基础数据的患者。主要结局为各试验定义的首次远处复发时间，忽略局部区域复发或对侧乳腺癌。通过Cox回归模型，调整患者和肿瘤特征、试验、治疗方案，比较不同诊断时期的10年远处复发风险。在2023年1月17日，EBCTCG数据库中652,258名早期乳腺癌患者中，来自151个随机试验的155,746名患者的患者级数据可用。ER阳性与ER阴性患者的远处肿瘤复发率均有类似改善，ER阳性疾病改善的80.5%，ER阴性疾病改善的89.8%由患者和肿瘤特征及治疗改善所解释，但仍具有统计学意义（p<0.0001）。近期诊断的患者更可能为淋巴结阴性。1990-1999年与2000-2009年期间的10年远处复发风险如下：淋巴结阴性，ER阳性为10.1%对7.3%，ER阴性为18.3%对11.9%；1-3个阳性淋巴结，ER阳性为19.9%对14.7%，ER阴性为31.9%对22.1%；4-9个阳性淋巴结，ER阳性为39.6%对28.5%，ER阴性为47.8%对36.5%。调整治疗后，2000年以后ER阳性疾病的复发率较1990年代降低了25%，ER阴性疾病降低了19%，且ER阳性疾病的改善在5年以上仍持续。试验结果的主要改善归因于低风险患者比例增加和辅助治疗的改善。调整后，自2000年以来诊断的女性远处复发率比1990年代低约五分之一。ER阳性疾病的远期复发风险仍存在，但较之前的报道低约十分之一。Cancer Research UK，英国医学研究委员会。

Distant recurrence in women with oestrogen receptor-positive early breast cancer persists at a constant rate for more than 20 years after diagnosis, with little equivalent data for oestrogen receptor-negative breast cancer. Using the database of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) we investigated rates of distant breast-cancer recurrence in oestrogen receptor-positive and oestrogen receptor-negative tumours and trends in outcomes over time.In this pooled analysis of randomised controlled trial data, patients in the EBCTCG database of more than 650 000 women in trials of treatment for early-stage breast cancer were screened for eligibility. Women were eligible if they were enrolled between 1990 and 2009 and newly diagnosed with oestrogen receptor-positive breast cancer and scheduled for at least 5 years of endocrine therapy, or oestrogen receptor-negative disease, and if they were younger than 75 years at diagnosis, had a tumour diameter of 50 mm or less, and fewer than ten positive axillary lymph nodes, and no evidence of distant metastases at entry. Trial of neoadjuvant therapy, or those in which adjuvant therapy was unclear, and women with oestrogen receptor-negative, progesterone receptor-positive disease, or those for whom outcome or baseline data were missing were excluded. The primary outcome was time to first distant recurrence as defined by each trial, ignoring any locoregional recurrence or contralateral breast cancer. 10-year risks of distant recurrence by period of diagnosis were compared using Cox regression adjusted for patient and tumour characteristics, trial, and assigned treatment.Of the 652 258 women with early breast cancer in the EBCTCG database on Jan 17, 2023, patient-level data were available from 151 randomised trials that included 155 746 women. Rates of distant tumour recurrence improved similarly in women with oestrogen receptor-positive and oestrogen receptor-negative tumours. 80·5% of the improvement for oestrogen receptor-positive disease and 89·8% of the improvement for eostrogen receptor-negative disease was explained by changes in patient and tumour characteristics and improved treatments, but remained significant (p<0·0001). More recently diagnosed patients were more likely to have node-negative disease. 10-year distant recurrence risks during 1990-99 versus 2000-09 were as follows: for node-negative disease, 10·1% versus 7·3% for oestrogen receptor-positive disease and 18·3% versus 11·9% for oestrogen receptor-negative disease; for disease with one to three positive nodes, 19·9% versus 14·7% for oestrogen receptor-positive disease and 31·9% versus 22·1% for oestrogen receptor-negative disease; and for disease with four to nine positive nodes, 39·6% versus 28·5% for oestrogen receptor-positive disease and 47·8% versus 36·5% for oestrogen receptor-negative disease. After adjustment for therapy, rates were reduced by 25% (oestrogen receptor-positive disease) and 19% (oestrogen receptor-negative disease) after 2000 versus the 1990s, with similar improvements observed in oestrogen receptor-positive disease beyond 5 years.Most of the improvement in trial outcomes is explained by a greater proportion of women with lower-risk disease entering trials and improved adjuvant treatment. After adjustment, women diagnosed since 2000 have about a fifth lower rate of distant recurrence than the 1990s. Long-term risks of distant recurrence for oestrogen receptor-positive disease remain, but are about a tenth lower now than in our previous report.Cancer Research UK, UK Medical Research Council.