Mukherjee Amrita, Gu Zheng, Chen Lie Hong, Chlebowski Rowan T, Potosky Arnold L, Haque Reina
Kaiser Permanente Southern California, Department of Research & Evaluation, Pasadena, CA, USA.
Lundquist Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA.
Cancer Epidemiol. 2025 Aug;97:102867. doi: 10.1016/j.canep.2025.102867. Epub 2025 Jun 20.
Breast cancer survivors have an increased risk of second primary cancers. However, the impact of comorbidity burden on risk of second primary non-breast cancer in breast cancer survivors is under-studied. We evaluated the association of comorbidity burden with risk of second primary non-breast cancer in breast cancer survivors.
In this retrospective cohort study, breast cancer patients aged ≥ 18 years diagnosed with in-situ, local, or regional first primary breast between 2008 and 2020 at Kaiser Permanente Southern California, were included. Patients were followed until 12/31/2021. Rates of second primary non-breast cancer were reported. Association of Elixhauser comorbidity index (ECI) and second primary cancer was reported using Cox proportional hazards regression.
Of 37,222 female breast cancer survivors included, 1701 (4.6 %) survivors developed second primary non-breast cancers during a median (interquartile range) follow-up of 5.2 (2.8-8.6) years. Nearly one-third (32.3 %) of the survivors had ECI score 3 + ; 22.6 % had ECI score 1-2; rest 27.0 % had zero ECI score. Incidence rates of second cancers were 561, 739, and 1064 per 100,000 person-years in survivors with ECI= 0, 1-2, and 3 + , respectively. In multivariable analyses, compared to survivors with ECI= 0, survivors with ECI scores 1-2 and 3 + had higher risk of second primary non-breast cancer [unadjusted HR (95 % CI): 1.32 (1.16-1.50) and 1.88 (1.65-2.14), respectively]. Higher risk of second primary non-breast cancer persisted in survivors with ECI score 3 + in the adjusted model [adjusted HR (95 % CI): 1.24 (1.08-1.43)].
Comorbidity burden appears to be correlated with an increased risk of second primary non-breast cancers in breast cancer survivors. Active surveillance and effective management of modifiable comorbidities may help in reducing second primary cancer risk in breast cancer survivors.
乳腺癌幸存者患第二原发性癌症的风险增加。然而，合并症负担对乳腺癌幸存者患第二原发性非乳腺癌风险的影响研究不足。我们评估了合并症负担与乳腺癌幸存者患第二原发性非乳腺癌风险之间的关联。
在这项回顾性队列研究中，纳入了2008年至2020年期间在南加州凯撒医疗中心诊断为原位、局部或区域原发性乳腺癌的18岁及以上乳腺癌患者。对患者进行随访直至2021年12月31日。报告第二原发性非乳腺癌的发生率。使用Cox比例风险回归报告埃利克斯豪泽合并症指数（ECI）与第二原发性癌症的关联。
在纳入的37222名女性乳腺癌幸存者中，1701名（4.6%）幸存者在中位（四分位间距）5.2（2.8 - 8.6）年的随访期间发生了第二原发性非乳腺癌。近三分之一（32.3%）的幸存者ECI评分为3+；22.6%的幸存者ECI评分为1 - 2；其余27.0%的幸存者ECI评分为零。ECI = 0、1 - 2和3+的幸存者中，第二癌症的发病率分别为每100000人年561、739和1064例。在多变量分析中，与ECI = 0的幸存者相比，ECI评分为1 - 2和3+的幸存者患第二原发性非乳腺癌的风险更高[未调整的风险比（95%置信区间）：分别为1.32（1.16 - 1.50）和1.88（1.65 - 2.14）]。在调整模型中，ECI评分为3+的幸存者患第二原发性非乳腺癌的较高风险仍然存在[调整后的风险比（95%置信区间）：1.24（1.08 - 1.43）]。
合并症负担似乎与乳腺癌幸存者患第二原发性非乳腺癌的风险增加相关。对可改变的合并症进行积极监测和有效管理可能有助于降低乳腺癌幸存者患第二原发性癌症的风险。
