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導(dǎo)管原位癌局限于乳腺導(dǎo)管內(nèi)原發(fā)部位，屬于乳腺癌最早期，又稱(chēng)零期乳腺癌，一旦浸潤(rùn)至乳腺導(dǎo)管外，即為乳腺浸潤(rùn)癌，又稱(chēng)浸潤(rùn)性或侵襲性乳腺癌。近幾十年來(lái)，導(dǎo)管原位癌發(fā)病率不斷升高，主要?dú)w因于乳腺癌篩查。目前已知，篩查檢出導(dǎo)管原位癌女性與普通人群女性相比，乳腺浸潤(rùn)癌發(fā)病率和乳腺癌死亡率高出1倍多，并且通常在診斷后至少20年。不過(guò)，許多女性在乳腺癌篩查之外被診斷出導(dǎo)管原位癌，要么因?yàn)樗齻儾辉诤Y查年齡范圍內(nèi)，要么因?yàn)樗齻兾磪⒓雍Y查，或者因?yàn)樗齻冊(cè)诤Y查間隔期間發(fā)病。對(duì)于非篩查檢出原位導(dǎo)管癌女性，隨后發(fā)生乳腺浸潤(rùn)癌和乳腺癌死亡的風(fēng)險(xiǎn)尚不清楚，風(fēng)險(xiǎn)隨著時(shí)間變化的方式亦不明確。因此，對(duì)于非篩查檢出導(dǎo)管原位癌，治療后隨訪的最佳時(shí)期和影像監(jiān)測(cè)頻率尚不確定。 2024年1月24日，國(guó)際四大醫(yī)學(xué)期刊之一、英國(guó)醫(yī)學(xué)會(huì)《英國(guó)醫(yī)學(xué)雜志》正刊發(fā)表牛津大學(xué)、英格蘭國(guó)家醫(yī)保局全國(guó)疾病登記中心的大數(shù)據(jù)分析報(bào)告，對(duì)1990～2018年英格蘭非篩查檢出導(dǎo)管原位癌女性、篩查檢出導(dǎo)管原位癌女性、普通人群女性發(fā)生乳腺浸潤(rùn)癌和乳腺癌相關(guān)死亡的長(zhǎng)期風(fēng)險(xiǎn)進(jìn)行了比較。 該人群隊(duì)列研究數(shù)據(jù)來(lái)自英格蘭國(guó)家醫(yī)保局全國(guó)疾病登記中心。1990～2018年，共計(jì)8萬(wàn)2009例英格蘭女性被診斷為導(dǎo)管原位癌，剔除原有乳腺癌史、診斷時(shí)年齡≥90歲、組織學(xué)為誤診或未確診、6個(gè)月內(nèi)已確診乳腺浸潤(rùn)癌或已化療或結(jié)束隨訪、記錄不完整的女性之后，其余2萬(wàn)7543例非篩查檢出導(dǎo)管原位癌、4萬(wàn)5148例篩查檢出導(dǎo)管原位癌。主要結(jié)局衡量指標(biāo)為乳腺浸潤(rùn)癌發(fā)病率和乳腺癌所致死亡。 
結(jié)果，截至2018年12月31日，非篩查檢出導(dǎo)管原位癌女性新發(fā)乳腺浸潤(rùn)癌3651例，與全國(guó)發(fā)病率相比高4.21倍（95%置信區(qū)間：4.07～4.35）。 整個(gè)隨訪期間，年齡45～70歲非篩查檢出導(dǎo)管原位癌女性乳腺浸潤(rùn)癌發(fā)病率與全國(guó)發(fā)病率相比，比值持續(xù)升高。 按導(dǎo)管原位癌診斷時(shí)年齡劃分，25年累計(jì)乳腺浸潤(rùn)癌風(fēng)險(xiǎn)： <45歲：27.3% 45～49歲：25.2% 50～59歲：21.7% 60～70歲：20.8%
908例非篩查檢出導(dǎo)管原位癌女性死于乳腺癌，與普通人群女性相比，乳腺癌所致死亡率高3.83倍（95%置信區(qū)間：3.59～4.09）。 整個(gè)隨訪期間，非篩查檢出導(dǎo)管原位癌女性與普通人群女性相比，乳腺癌所致死亡率比值持續(xù)升高。 按導(dǎo)管原位癌診斷時(shí)年齡劃分的25年累計(jì)乳腺癌所致死亡風(fēng)險(xiǎn)為： <45歲：7.6% 45～49歲：5.8% 50～59歲：5.9% 60～70歲：6.2%
對(duì)于50～64歲有資格接受?chē)?guó)家醫(yī)保局乳腺篩查的女性，非篩查檢出與篩查檢出原位導(dǎo)管癌相比： 對(duì)于2萬(wàn)2753例進(jìn)行手術(shù)的單側(cè)導(dǎo)管原位癌女性，乳房切除術(shù)與保乳手術(shù)±放療相比，25年累計(jì)同側(cè)乳腺浸潤(rùn)癌發(fā)病率顯著較低： 乳房切除術(shù)：8.2%（95%置信區(qū)間：7.0%～9.4%） 保乳手術(shù)＋放療：19.8%（95%置信區(qū)間：16.2%～23.4%） 保乳手術(shù)未放療：20.6%（95%置信區(qū)間：18.7%～22.4%）
不過(guò)，乳房切除術(shù)與保乳手術(shù)±放療相比，25年累計(jì)乳腺癌死亡率相似： 乳房切除術(shù)：6.5%（95%置信區(qū)間：4.9%～10.9%） 保乳手術(shù)＋放療：8.6%（95%置信區(qū)間：5.9%～15.5%） 保乳手術(shù)未放療：7.8%（95%置信區(qū)間：6.3%～11.5%）
因此，該研究結(jié)果表明：非篩查檢出導(dǎo)管原位癌女性與普通人群女性相比，診斷后至少25年內(nèi)乳腺浸潤(rùn)癌和乳腺癌死亡長(zhǎng)期風(fēng)險(xiǎn)高4倍左右。此外，非篩查檢出與篩查檢出原位導(dǎo)管癌女性相比，長(zhǎng)期風(fēng)險(xiǎn)更高。乳房切除術(shù)與保乳手術(shù)±放療相比，乳腺浸潤(rùn)癌風(fēng)險(xiǎn)顯著較低，乳腺癌死亡風(fēng)險(xiǎn)相似。 對(duì)此，荷蘭癌癥研究院、列文虎克醫(yī)院、萊頓大學(xué)醫(yī)學(xué)中心發(fā)表同期評(píng)論：非篩查檢出導(dǎo)管原位癌的乳腺浸潤(rùn)癌和乳腺癌死亡風(fēng)險(xiǎn)較高，需要加強(qiáng)監(jiān)測(cè)。BMJ. 2024 Jan 24;384:e075498. IF: 105.7Invasive breast cancer and breast cancer death after non-screen detected ductal carcinoma in situ from 1990 to 2018 in England: population based cohort study.Gurdeep S Mannu, Zhe Wang, statistician, David Dodwell, John Broggio, Jackie Charman, Sarah C Darby.University of Oxford, Oxford, UK; National Disease Registration Service, NHS England, Birmingham, UK.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 27543 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 22753 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.DOI: 10.1136/bmj-2023-075498BMJ. 2024 Jan 24;384:q22. IF: 105.7Invasive breast cancer and breast cancer death after non-screen detected ductal carcinoma in situ.Marjanka K Schmidt, Esther H Lips, Renée SJM Schmitz, Ellen Verschuur, Jelle Wesseling.Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Netherlands; Leiden University Medical Center, Leiden, Netherlands; Patient author, Precision project, Netherlands.
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