乳腺癌第二原发恶性肿瘤风险因素

　　随着乳腺癌患者的生存时间不断延长，第二原发恶性肿瘤的发生率也在不断增加。对于癌症存活者，癌症治疗可能引起其他恶性肿瘤的担忧日益严重。

　　2019年3月22日，国际抗癌联盟《国际癌症杂志》清样发表中国四川大学华西医院、重庆医科大学附属第一医院、美国奥古斯塔大学佐治亚医学院的研究报告，通过大数据分析，调查了乳腺癌第二原发恶性肿瘤的发生率及其相关风险因素。

　　该嵌套病例对照研究根据美国国家癌症研究所（NCI）监测流行病学最终结果（SEER）数据库对乳腺癌患者第二原发恶性肿瘤发生率及其相关风险因素进行评定。将有第二原发恶性肿瘤的乳腺癌患者定义为病例组，将无第二原发恶性肿瘤的乳腺癌患者定义为对照组。根据首次原发乳腺癌诊断年份，将病例组与对照组按1∶5的比例进行倾向评分匹配，匹配后1998～2013年共计乳腺癌患者97242例。按年龄组和癌症部位分层的乳腺癌患者第二原发恶性肿瘤发生率与普通人群标准化发生率进行比较，通过多因素比例风险回归模型分析第二原发性恶性肿瘤的风险因素。

　　结果，乳腺癌患者与普通人群相比，对所有癌症部位进行校正后，第二原发恶性肿瘤的标准化发生率风险高12.94倍（P<0.001）并且与年龄成反比。第二原发恶性肿瘤风险与以下人口统计学和临床因素显著相关：

• 年龄（40～59岁、60～79岁、≥80岁与18～39岁相比，风险分别高33%、139%、184%）

• 种族（黑人与白人相比，风险高12%）

• 病理（乳腺小叶癌与乳腺导管癌相比，风险高15%）

• 放疗（放疗与否相比，风险高33%）

• 婚姻（已婚与单身相比，风险低12%）

• 受体（雌激素受体阳性与阴性相比，风险低15%）

　　按对侧乳房和非乳房第二原发恶性肿瘤进行分层的亚组分析结果相似。乳房切除与乳房保留相比、化疗与不化疗相比，第二原发恶性肿瘤风险相似。

　　因此，该研究结果表明，除了年龄、种族、病理、婚姻、雌激素受体等无法改变的因素，放疗患者第二原发恶性肿瘤发生风险显著增加，故有必要谨慎管理放疗剂量，以尽可能减少风险。

相关阅读

• 乳腺癌第二原发癌生存与化疗风险

Int J Cancer. 2019 Mar 22. [Epub ahead of print]

Incidence of second primary malignancy after breast cancer and related risk factors—is breast conserving surgery safe? A nested case-control study.

Li Z, Wang K, Shi Y, Zhang X, Wen J.

West China Hospital, Sichuan University, Chengdu, China; The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China; Medical College of Georgia, Augusta University, Augusta, GA, USA.

What's new? For cancer survivors, the idea that the treatment that saved them might induce another malignancy weighs heavily. In this study, the authors investigated the risk factors for second primary malignancies among breast cancer survivors, using information from the SEER database. Mastectomy and breast-conserving surgery carry similar risk of second primary malignancy, they found. However, patients who underwent radiotherapy had significant increased risk of developing a second primary malignancy. Doses of radiotherapy, the authors suggest, need to be carefully managed to minimize risk.

Risk of second primary malignancy (SPM) is increasing. We aimed to assess the incidence and related risk factors of SPM among breast cancer (BC) patients from this nested case-control study using the SEER database. BC patients with SPM were identified as the case group and SPM-free patients were defined as the control group. Propensity score matching of cases with controls by the year of the first primary BC diagnosis was conducted at the ratio of 1:5, and 97,242 BC patients were enrolled from 1998 to 2013 after the matching. The incidence of SPM in BC patients stratified by age groups and cancer sites was compared to the general population using the adjusted standardized incidence ratio (SIR) and the risk factors for SPM were examined using Cox proportional hazard regressions. Our study showed BC patients had excess risk for SPM than the general population (adjusted SIR for all cancer sites = 12.94, p < 0.001) and the incidence of SPM among them decreased with age. The risk of SPM was significantly related to the following demographical and clinical variables: age (40-59 vs. 18-39, HR = 1.33; 60-79 vs. 18-39, HR = 2.39; ≥80 vs. 18-39, HR = 2.84), race (black vs. white, HR = 1.12), histological type (lobular BC vs. ductal BC, HR = 1.15), radiotherapy (HR = 1.33), marital status (married vs. single, HR = 0.88) and estrogen receptor status (positive vs. negative, HR = 0.85). Consistent results were found in subgroup analysis stratified by contralateral-breast SPMs and nonbreast SPMs.

KEYWORDS: breast cancer; breast-conserving surgery; radiotherapy; risk factor; second primary malignancy

PMID: 30861567

DOI: 10.1002/ijc.32259