McGale Paul, Dodwell David, Challenger Andrew, Cutter David, Williams Alexander, Broggio John, Darby Sarah, Mannu Gurdeep, Taylor Carolyn
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Oxford University Hospitals NHS Trust, Oxford, UK.
BMJ. 2025 Aug 27;390:e083975. doi: 10.1136/bmj-2024-083975.
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.
Population based observational cohort study.
Routinely collected data from the National Cancer Registration and Analysis Service for England.
All 476 373 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.
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.
Although 64 747 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 64 747 second cancers and 7% of the 15 813 excess second cancers in the cohort may be attributable to adjuvant therapies.
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.
描述早期浸润性乳腺癌患者初次手术后发生第二种非乳腺癌原发性癌症及对侧乳腺癌的长期风险。
基于人群的观察性队列研究。
从英国国家癌症登记与分析服务机构常规收集的数据。
1993年1月至2016年12月在英国登记的所有476373例以乳腺癌作为首个浸润性（索引）癌症的女性，随访至2021年10月。
后续原发性癌症的发生率和累积风险，与一般人群中发生的情况相比较；与患者特征、索引肿瘤及辅助治疗的关联。
尽管64747名女性发生了第二种原发性癌症，但与一般人群的风险相比，绝对超额风险较小。到20年时，13.6%（95%置信区间13.5%至13.7%）的女性发生了非乳腺癌，比一般人群预期的多2.1%（2.0%至2.3%），5.6%（5.5%至5.6%）的女性发生了对侧乳腺癌，比一般人群预期的多3.1%（3.0%至3.2%）。对侧乳腺癌的绝对超额风险在年轻女性中高于老年女性。在特定类型的非乳腺癌中，20年的最大绝对超额风险是子宫癌和肺癌。尽管子宫癌、软组织癌、骨与关节癌、唾液腺癌以及急性白血病的标准化发病比超过一般人群至少1.5倍，但每种非乳腺癌类型在20年时的绝对超额风险<1%。当根据辅助治疗对患者进行分类时，放疗与对侧乳腺癌和肺癌风险增加相关，内分泌治疗与子宫癌风险增加相关（但对侧乳腺癌风险降低），化疗与急性白血病风险增加相关。这些与随机试验中报告的效应一致，但也发现软组织癌、头颈癌、卵巢癌和胃癌存在正相关，而这些在试验中此前未被观察到。这表明该队列中所有64747例第二种癌症中的约2%以及15813例额外第二种癌症中的7%可能归因于辅助治疗。
早期浸润性乳腺癌治疗女性发生第二种原发性癌症的风险略高于一般人群中的女性。对侧乳腺癌约占总体增加风险的60%，年轻女性风险更高。与辅助治疗相关的风险较小。
