Objectives To evaluate the long term risks of invasive breast cancer and death related to breast cancer after non-screen detected ductal carcinoma in situ. Risks for women in the general population and for women diagnosed with ductal carcinoma in situ via the screening programme were compared. Design Population based cohort study. Setting Data from the National Disease Registration Service. Participants All 27 543 women in England who were diagnosed with ductal carcinoma in situ, outside the NHS breast screening programme, during 1990 to 2018. Main outcome measures Incident invasive breast cancer and death caused by breast cancer. Results By 31 December 2018, 3651 women with non-screen detected ductal carcinoma in situ had developed invasive breast cancer, more than four times higher than expected from national cancer incidence rates (ratio of observed to expected rate was 4.21 (95% conference interval 4.07 to 4.35)). The ratio of observed to expected rate of developing invasive breast cancer remained increased throughout follow-up among women aged <45-70 years. The 25 year cumulative risks of invasive breast cancer by age at diagnosis of ductal carcinoma in situ were 27.3% for <45 years, 25.2% for 45-49 years, 21.7% for 50-59 years, and 20.8% for 60-70 years. 908 women died of breast cancer, almost four times higher than that expected from breast cancer death rates in the general population (ratio of observed to expected rate 3.83 (3.59 to 4.09)). The ratio of observed to expected rate of mortality attributed to breast cancer remained increased throughout follow-up. The 25 year cumulative risks of breast cancer death by age at ductal carcinoma in situ diagnosis were 7.6% for <45 years, 5.8% for 45-49 years, 5.9% for 50-59 years, and 6.2% for 60-70 years. Among women aged 50-64 years, and therefore eligible for breast screening by the NHS, the ratio of observed to expected rate of invasive breast cancer in women with non-screen detected compared with screen detected ductal carcinoma in situ was 1.26 (95% conference interval 1.17 to 1.35), while the ratio for mortality from breast cancer was 1.37 (1.17 to 1.60). Among 22 753 women with unilateral ductal carcinoma in situ undergoing surgery, those who had mastectomy rather than breast conserving surgery had a lower 25 year cumulative rate of ipsilateral invasive breast cancer (mastectomy 8.2% (95% conference interval 7.0% to 9.4%), breast conserving surgery with radiotherapy 19.8% (16.2% to 23.4%), and breast conserving surgery with no radiotherapy recorded 20.6% (18.7% to 22.4%)). However, reductions did not translate into a lower 25 year cumulative rate of deaths attributable to breast cancer (mastectomy 6.5% (4.9% to 10.9%), breast conserving surgery with radiotherapy 8.6% (5.9% to 15.5%), breast conserving surgery with no radiotherapy recorded 7.8% (6.3% to 11.5%)). Conclusions For at least 25 years after their diagnosis, women with non-screen detected ductal carcinoma in situ had higher long term risks of invasive breast cancer and breast cancer death than women in the general population. Additionally, they had higher long term risks than women with screen detected ductal carcinoma in situ. Mastectomy was associated with lower risks of invasive breast cancer than breast conserving surgery, even when accompanied by radiotherapy. However, risks of breast cancer death appeared similar for mastectomy, breast conserving surgery with radiotherapy, and breast conserving surgery with no radiotherapy recorded. De-personalised study data may be made available on request to accredited researchers who submit a proposal that is approved by NHS Digital’s Data Access Request Service.

中文翻译：

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1990年至2018年英格兰侵袭性乳腺癌和非筛查检测出导管原位癌后乳腺癌死亡：基于人群的队列研究

目的 评估非筛查检测出导管原位癌后发生浸润性乳腺癌和与乳腺癌相关的死亡的长期风险。比较了普通人群中女性和通过筛查计划诊断为导管原位癌的女性的风险。设计基于人群的队列研究。设置来自国家疾病登记服务的数据。参与者 1990 年至 2018 年间，在 NHS 乳腺筛查计划之外被诊断出患有导管原位癌的所有 27 543 名英格兰女性。主要结果指标是浸润性乳腺癌发生率和乳腺癌导致的死亡。结果 截至 2018 年 12 月 31 日，3651 名未筛查出导管原位癌的女性发展为浸润性乳腺癌，比全国癌症发病率预期高出四倍多（观察率与预期率之比为 4.21（95% 会议间隔为 4.07）至 4.35))。在年龄 <45-70 岁的女性中，在整个随访过程中，观察到的浸润性乳腺癌发生率与预期发生率的比率持续增加。按诊断导管原位癌时年龄划分的浸润性乳腺癌 25 年累积风险为：<45 岁者为 27.3%，45-49 岁者为 25.2%，50-59 岁者为 21.7%，60-70 岁者为 20.8% 。908 名妇女死于乳腺癌，几乎是一般人群乳腺癌死亡率预期的四倍（观察值与预期值之比 3.83（3.59 至 4.09））。在整个随访过程中，观察到的乳腺癌死亡率与预期死亡率的比率持续增加。按导管原位癌诊断年龄划分的 25 年累积乳腺癌死亡风险分别为：<45 岁者为 7.6%，45-49 岁者为 5.8%，50-59 岁者为 5.9%，60-70 岁者为 6.2%。在 50-64 岁、因此有资格接受 NHS 乳腺筛查的女性中，未筛查发现的女性中观察到的浸润性乳腺癌与筛查发现的原位导管癌的女性相比，观察到的浸润性乳腺癌发生率与预期的比率为 1.26（95%区间1.17至1.35），而乳腺癌死亡率的比率为1.37（1.17至1.60）。在 22 753 名接受手术的单侧导管原位癌女性中，接受乳房切除术而非保乳手术的女性 25 年累积同侧浸润性乳腺癌发生率较低（乳房切除术为 8.2%（95% 会议间隔为 7.0% 至 9.4%），接受放疗的保乳手术占 19.8%（16.2% 至 23.4%），不接受放疗的保乳手术占 20.6%（18.7% 至 22.4%）。然而，减少并没有降低 25 年乳腺癌累积死亡率（乳房切除术 6.5%（4.9% 至 10.9%），保乳手术加放疗 8.6%（5.9% 至 15.5%），保乳手术加放疗 8.6%（5.9% 至 15.5%），保乳手术加放疗）。未记录放射治疗的占 7.8%（6.3% 至 11.5%））。结论 在确诊后至少 25 年内，与一般人群中的女性相比，未筛查发现导管原位癌的女性罹患浸润性乳腺癌和乳腺癌死亡的长期风险更高。此外，与筛查发现原位导管癌的女性相比，她们的长期风险更高。与保乳手术相比，即使伴随放疗，乳房切除术与浸润性乳腺癌的风险较低相关。然而，乳房切除术、放疗保乳手术和未记录放疗的保乳手术的乳腺癌死亡风险似乎相似。经认可的研究人员可以根据要求提供去个性化的研究数据，这些研究人员提交的提案经 NHS Digital 的数据访问请求服务批准。