近日，英国牛津大学Carolyn Taylor团队研究了1993-2016年英国475000名诊断为早期侵袭性癌症妇女患第二种癌症的风险。该项研究成果发表在2025年8月27日出版的《英国医学杂志》上。

该研究旨在描述早期浸润性乳腺癌患者在原发手术后发生第二非乳腺癌原发癌和对侧乳腺癌的长期风险。

研究组进行了一项基于人群的观察队列研究，定期从英国国家癌症登记和分析服务中心收集数据。1993年1月到2016年12月，在英格兰登记了476373名乳腺癌患者，她们的第一次浸润性（指数）癌症是乳腺癌，随访至2021年10月。主要结局为与普通人群相比，继发原发性癌症的发病率和累积风险；与患者特征、指数肿瘤和辅助治疗的关联。

尽管64747名妇女患第二原发性癌症，与一般人群相比，绝对超额风险很小。20年后，13.6%（95%置信区间13.5%至13.7%）的女性发展为非乳腺癌，比一般人群的预期高出2.1%(2.0%至2.3%)，5.6%（5.5%至5.6%）的女性发展为对侧乳腺癌，比预期高出3.1%（3.0%至3.2%）。年轻女性患对侧乳腺癌的绝对风险高于年长女性。在特定类型的非乳腺癌中，最大的20年绝对超额风险是子宫癌和肺癌。虽然子宫癌、软组织癌、骨关节癌、唾液腺癌以及急性白血病的标准化发病率比一般人群的发病率至少高出1.5倍，但对于每一种非乳腺癌类型，20年的绝对超额风险为1%。

当患者根据辅助治疗进行分类时，放疗与对侧乳腺癌和肺癌增加有关，内分泌治疗与子宫癌增加有关（但与对侧乳腺癌减少有关），化疗与急性白血病增加有关。这与随机试验报告的效果一致，但也发现了软组织、头颈部、卵巢癌和胃癌的正相关，这些在以前的试验中没有观察到。这表明，队列中所有64747例第二癌症中约有2%和15813例多余的第二种癌中约有7%可归因于辅助治疗。

研究结果表明，接受早期浸润性乳腺癌治疗的女性患第二原发癌的风险略高于普通人群中的女性。对侧乳腺癌占总体增加的60%左右，年轻女性的风险更高。与辅助治疗相关的风险很小。

附：英文原文

Title: Second cancers in 475 000 women with early invasive breast cancer diagnosed in England during 1993-2016: population based observational cohort study

Author: Paul McGale, David Dodwell, Andrew Challenger, David Cutter, Alexander Williams, John Broggio, Sarah Darby, Gurdeep Mannu, Carolyn Taylor

Issue&Volume: 2025/08/27

Abstract:

Objective To describe long term risks of second non-breast primary cancers and contralateral breast cancers among women with early invasive breast cancer after primary surgery.

Design Population based observational cohort study.

Setting Routinely collected data from the National Cancer Registration and Analysis Service for England.

Participants All 476373 women with breast cancer as their first invasive (index) cancer registered in England from January 1993 to December 2016 with follow-up until October 2021.

Main outcome measures Rates and cumulative risks of subsequent primary cancers, compared with those occurring in the general population; associations with characteristics of patients, index tumours, and adjuvant treatments.

Results Although 64747 women developed a second primary cancer, the absolute excess risks compared with risks in the general population were small. By 20 years, 13.6% (95% confidence interval 13.5% to 13.7%) of women had developed a non-breast cancer, 2.1% (2.0% to 2.3%) more than expected in the general population, and 5.6% (5.5% to 5.6%) had developed a contralateral breast cancer, 3.1% (3.0% to 3.2%) more than expected. The absolute excess risk of contralateral breast cancer was greater in younger than in older women. Among specific types of non-breast cancer, the largest 20 year absolute excess risks were for uterine and lung cancers. Although for cancers of the uterus, soft tissue, bones and joints, and salivary glands, as well as acute leukaemias, standardised incidence ratios exceeded those of the general population by a factor of at least 1.5, absolute excess risks at 20 years were <1% for every individual non-breast cancer type. When patients were categorised according to adjuvant treatment, radiotherapy was associated with increased contralateral breast and lung cancer, endocrine therapy with increased uterine cancer (but reduced contralateral breast cancer), and chemotherapy with increased acute leukaemia. These were consistent with effects reported in randomised trials, but positive associations for soft tissue, head and neck, ovarian, and stomach cancers were also identified, and these have not previously been observed in trials. This suggested that approximately 2% of all the 64747 second cancers and 7% of the 15813 excess second cancers in the cohort may be attributable to adjuvant therapies.

Conclusions The risk of a second primary cancer in women treated for early invasive breast cancer is slightly higher than for women in the general population. Contralateral breast cancer accounts for around 60% of the overall increase, with higher risks in younger women. The risk associated with adjuvant therapies is small.

DOI: 10.1136/bmj-2024-083975

Source: https://www.bmj.com/content/390/bmj-2024-083975