首页 > 文章详情

十五万早期乳腺癌二十年复发变迁

10月14日

来源：《柳叶刀》正刊, SIBCS

1983年由英国牛津大学发起成立的早期乳腺癌试验者协作组（EBCTCG）每年邀请国际知名乳腺癌专家（其中包括来自中国医学科学院肿瘤医院、复旦大学附属肿瘤医院、上海交通大学医学院的乳腺癌专家）对全球发表的早期乳腺癌大规模随机对照试验患者级数据及其长期随访结果进行汇总分析，并发表于全球各大顶级医学期刊，提供了解决临床重要问题的权威证据。 2017年， EBCTCG发表了对 1976至2011年88项术后治疗试验6万2923例雌激素受体阳性早期乳腺癌女性长期结局的荟萃分析，发现完成内分泌治疗后至少 20年期间远处复发率达10%至41% 。不过，目前关于雌激素受体阴性早期乳腺癌复发率的数据极少。

2024年10月10日，国际四大医学期刊之首、创刊201周年的英国《柳叶刀》正刊第19次发表 EBCTCG史诗级研究报告，利用EBCTCG数据库，对近 20年期间参加 151项临床试验的 15万 5746例女性雌激素受体阳性和雌激素受体阴性早期乳腺癌远处复发率及其结局变化趋势进行了汇总分析。该研究由英国癌症研究中心和英国医学研究委员会资助。

该随机对照试验数据汇总分析首先对EBCTCG数据库超过65万例参加早期乳腺癌治疗试验的女性患者进行筛选，如果入组于1990至2009年，并且新诊断雌激素受体阳性早期乳腺癌并计划至少5年内分泌治疗，或者雌激素受体阴性早期乳腺癌并且诊断时年龄小于75岁、肿瘤直径≤50毫米、腋窝淋巴结阳性少于10枚、入组时无远处转移证据，那么符合入选条件。术前治疗试验、术后治疗不明确的试验、雌激素受体阴性孕激素受体阳性乳腺癌女性、缺少结局或者基线数据的女性被剔除。主要结局为各个试验定义的首次远处复发时间，忽略任何局部区域复发或对侧乳腺癌。通过多因素比例风险回归模型，对患者特征和肿瘤特征、不同试验以及指定治疗方法等各种影响因素进行校正后，对按诊断分期划分的10年远处复发率进行比较。

结果，2023年1月17日数据采集当天EBCTCG数据库早期乳腺癌女性数据共计 65万2258例，其中 151项随机试验包括 15万5746例女性可以获得患者级数据。

雌激素受体阳性与雌激素受体阴性乳腺癌女性相比，远处复发率改善相似。

80.5%的雌激素受体阳性乳腺癌改善和 89.8%的雌激素受体阴性乳腺癌改善可以归因于患者特征和肿瘤特征变化以及治疗方法改善，1990至1999年、2000至2004年、2005至2009年相比，远处复发率显著降低（P<0.0001）。

近年来确诊患者淋巴结阴性比例较高。

1990至1999年与 2000至2009年的10年远处复发率相比：

淋巴结阴性

雌激素受体阳性：10.1%比7.3%
雌激素受体阴性：18.3%比11.9%

淋巴结阳性1至3枚

雌激素受体阳性：19.9%比14.7%
雌激素受体阴性：31.9%比22.1%

淋巴结阳性4至9枚

雌激素受体阳性：39.6%比28.5%
雌激素受体阴性：47.8%比36.5%

对治疗方法进行校正后， 2000年后与 1990年代相比，雌激素受体阳性乳腺癌、雌激素受体阴性乳腺癌的远处复发率分别降低 25% 、 19% ，雌激素受体阳性乳腺癌5年后远处复发率也有类似改善。

因此，该研究结果表明，试验结局改善大部分由于参加试验的低风险乳腺癌女性比例增加以及术后治疗方法改善。对治疗方法进行校正后，2000年后与1990年代确诊女性相比，远处复发率降低大约五分之一。雌激素受体阳性乳腺癌长期远处复发风险仍然存在，但是现在比以前的报告降低大约十分之一。

对此，美国哈佛大学医学院、达纳法伯癌症研究院、达纳法伯布莱根癌症中心、意大利米兰大学发表同期评论：乳腺癌管理进展。

Lancet. 2024 Oct 10;404(10461):1407-1418. IF: 98.4

Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155746 women in 151 trials.

Early Breast Cancer Trialists' Collaborative Group.

BACKGROUND : 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.

METHODS : In this pooled analysis of randomised controlled trial data, patients in the EBCTCG database of more than 650000 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.

FINDINGS : Of the 652258 women with early breast cancer in the EBCTCG database on Jan 17, 2023, patient-level data were available from 151 randomised trials that included 155746 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.

INTERPRETATION : 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.

FUNDING : Cancer Research UK, UK Medical Research Council.

DOI : 10.1016/S0140-6736(24)01745-8

Lancet. 2024 Oct 12;404(10461):1376-1378. IF: 98.4

Progress in breast cancer management.

Paolo Tarantino, Sara M Tolaney.

Dana-Farber Cancer Institute, Boston, MA, USA; Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; University of Milan, Milan, Italy.

DOI : 10.1016/S0140-6736(24)01823-3