Grantzau Trine, Overgaard Jens
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Radiother Oncol. 2016 Dec;121(3):402-413. doi: 10.1016/j.radonc.2016.08.017. Epub 2016 Sep 14.
Radiotherapy plays an essential role in early breast cancer treatment, but is also associated with an increased risk of second malignancies decades after the exposure.
We systematically searched the data-bases Medline/Pubmed, Cochrane, Embase, and Cinahl, for cohort studies estimating the risk of second non-breast cancer after primary breast cancer. Every included study was to report the standardized incidence ratio [SIR] of second cancers, comparing the risk among either irradiated or unirradiated female breast cancer patients to the risk of the general female population. From each study the SIRs were extracted and then pooled using random-effects meta-analysis. SIRs were pooled as an overall estimate and according to time since breast cancer diagnosis.
22 studies were eligible for inclusion, comprising 245,575 irradiated and 277,164 non-irradiated women. Irradiated patients had an overall increased risk of second non-breast cancer, with a SIR of 1.23 (95% confidence interval [CI] 1.12-1.36). For non-irradiated patients the SIR was 1.08 (95% CI, 1.03-1.13). For irradiated patients the incidence of second cancers including the lung, esophagus, thyroid and connective tissues progressively increased over time, peaking at 10-15years following breast cancer diagnosis. Summary estimates at ⩾15years after breast cancer irradiation were 1.91 for lung, 2.71 for esophagus, 3.15 for thyroid and 6.54 at ⩾10years for second sarcomas. Non-irradiated patients had no increased risk of second lung or esophagus cancer, neither overall nor over time. For non-irradiated patients' risk of second thyroid cancer (SIR 1.21) and sarcomas (SIR 1.42) were increased overall, but with no remaining risk ⩾10 after breast cancer.
Radiotherapy for breast cancer is associated with an excess risk of second non-breast cancer, overall and in organs adjacent to the previous treatment fields. The growing number of long-term survivors after breast cancer highlights the need for an improved individualized approach toward identifying patients with an expected benefit from radiation and patients with no added radiation-benefit.
放射治疗在早期乳腺癌治疗中起着至关重要的作用，但在放疗数十年后，发生第二原发性恶性肿瘤的风险也会增加。
我们系统检索了Medline/Pubmed、Cochrane、Embase和Cinahl数据库，查找评估原发性乳腺癌后发生第二原发性非乳腺癌风险的队列研究。每项纳入研究均需报告第二原发性癌症的标准化发病比（SIR），将接受放疗或未接受放疗的女性乳腺癌患者的风险与普通女性人群的风险进行比较。从每项研究中提取SIR，然后采用随机效应荟萃分析进行汇总。SIR作为总体估计值进行汇总，并根据乳腺癌诊断后的时间进行汇总。
22项研究符合纳入标准，包括245,575例接受放疗的女性和277,164例未接受放疗的女性。接受放疗的患者发生第二原发性非乳腺癌的总体风险增加，SIR为1.23（95%置信区间[CI] 1.12 - 1.36）。未接受放疗的患者SIR为1.08（95% CI，1.03 - 1.13）。对于接受放疗的患者，包括肺癌、食管癌、甲状腺癌和结缔组织癌在内的第二原发性癌症的发病率随时间逐渐增加，在乳腺癌诊断后10 - 15年达到峰值。乳腺癌放疗后≥15年的汇总估计值为：肺癌1.91，食管癌2.71，甲状腺癌3.15，第二原发性肉瘤在≥10年时为6.54。未接受放疗的患者发生第二原发性肺癌或食管癌的风险总体上以及随时间均未增加。对于未接受放疗的患者，第二原发性甲状腺癌（SIR 1.21）和肉瘤（SIR 1.42）的总体风险增加，但在乳腺癌后≥10年时无剩余风险。
乳腺癌放疗与发生第二原发性非乳腺癌的额外风险相关，总体上以及在先前治疗区域附近的器官中。乳腺癌长期幸存者数量的增加凸显了需要改进个体化方法，以识别可能从放疗中获益的患者和无放疗额外获益的患者。
