Circulating Leukocyte Subsets Before and After a Breast Cancer Diagnosis and Therapy

Importance 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. Objective 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. Exposures Breast cancer status and, among breast cancer survivors, cancer treatment type (chemotherapy, radiotherapy, endocrine therapy, or surgery). Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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.