Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
Department of Breast Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
JAMA Netw Open. 2024 Feb 5;7(2):e2356113. doi: 10.1001/jamanetworkopen.2023.56113.
Changes in leukocyte composition often precede chronic disease onset. Patients with a history of breast cancer (hereinafter referred to as breast cancer survivors) are at increased risk for subsequent chronic diseases, but the long-term changes in peripheral leukocyte composition following a breast cancer diagnosis and treatment remain unknown.
To examine longitudinal changes in peripheral leukocyte composition in women who did and did not develop breast cancer and identify whether differences in breast cancer survivors were associated with specific treatments.
DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, paired blood samples were collected from 2315 women enrolled in The Sister Study, a US-nationwide prospective cohort study of 50 884 women, at baseline (July 2003 to March 2009) and follow-up (October 2013 to March 2015) home visits, with a mean (SD) follow-up interval of 7.6 (1.4) years. By design, approximately half of the included women had been diagnosed and treated for breast cancer after enrollment and before the second blood draw. A total of 410 women were included in the present study, including 185 breast cancer survivors and 225 who remained free of breast cancer over a comparable follow-up period. Data were analyzed from April 21 to September 9, 2022.
Breast cancer status and, among breast cancer survivors, cancer treatment type (chemotherapy, radiotherapy, endocrine therapy, or surgery).
Blood DNA methylation data were generated in 2019 using a genome-wide methylation screening tool and deconvolved to estimate percentages of 12 circulating leukocyte subsets.
Of the 410 women included in the analysis, the mean (SD) age at enrollment was 56 (9) years. Compared with breast cancer-free women, breast cancer survivors had decreased percentages of circulating eosinophils (-0.45% [95% CI, -0.87% to -0.03%]; P = .03), total CD4+ helper T cells (-1.50% [95% CI, -2.56% to -0.44%]; P = .01), and memory B cells (-0.22% [95% CI, -0.34% to -0.09%]; P = .001) and increased percentages of circulating naive B cells (0.46% [95% CI, 0.17%-0.75%]; P = .002). In breast cancer survivor-only analyses, radiotherapy was associated with decreases in total CD4+ T cell levels, whereas chemotherapy was associated with increases in naive B cell levels. Surgery and endocrine therapy were not meaningfully associated with leukocyte changes.
In this cohort study of 410 women, breast cancer survivors experienced lasting changes in peripheral leukocyte composition compared with women who remained free of breast cancer. These changes may be related to treatment with chemotherapy or radiotherapy and could influence future chronic disease risk.
白细胞组成的变化通常先于慢性疾病的发作。有乳腺癌病史的患者（以下简称乳腺癌幸存者）随后发生慢性疾病的风险增加，但乳腺癌诊断和治疗后外周血白细胞组成的长期变化尚不清楚。
检查未发生和发生乳腺癌的女性外周白细胞组成的纵向变化，并确定乳腺癌幸存者的差异是否与特定的治疗方法有关。
设计、地点和参与者：在这项前瞻性队列研究中，从参加美国全国性前瞻性队列研究“姐妹研究”的 50884 名女性中抽取了 2315 名女性的配对血样，该研究在基线（2003 年 7 月至 2009 年 3 月）和随访（2013 年 10 月至 2015 年 3 月）的家庭访问中进行，平均（SD）随访间隔为 7.6（1.4）年。按设计，大约一半的纳入女性在入组前和第二次采血前被诊断和治疗过乳腺癌。共有 410 名女性纳入本研究，包括 185 名乳腺癌幸存者和 225 名在可比随访期间未患乳腺癌的女性。数据分析于 2022 年 4 月 21 日至 9 月 9 日进行。
乳腺癌状况以及乳腺癌幸存者中癌症治疗类型（化疗、放疗、内分泌治疗或手术）。
在 2019 年使用全基因组甲基化筛选工具生成血液 DNA 甲基化数据，并进行反卷积以估计 12 种循环白细胞亚群的百分比。
在纳入分析的 410 名女性中，入组时的平均（SD）年龄为 56（9）岁。与无乳腺癌的女性相比，乳腺癌幸存者的循环嗜酸性粒细胞百分比降低（-0.45%[95%CI，-0.87%至-0.03%]；P =.03）、总 CD4+辅助 T 细胞百分比降低（-1.50%[95%CI，-2.56%至-0.44%]；P =.01）和记忆 B 细胞百分比降低（-0.22%[95%CI，-0.34%至-0.09%]；P =.001），而循环幼稚 B 细胞百分比升高（0.46%[95%CI，0.17%-0.75%]；P =.002）。在仅乳腺癌幸存者的分析中，放疗与总 CD4+T 细胞水平下降有关，而化疗与幼稚 B 细胞水平升高有关。手术和内分泌治疗与白细胞变化无明显相关性。
在这项对 410 名女性的队列研究中，与未患乳腺癌的女性相比，乳腺癌幸存者经历了外周白细胞组成的持久变化。这些变化可能与化疗或放疗有关，可能会影响未来的慢性疾病风险。
