Sustained Decreases in Peripheral Lymphocytes After Adjuvant Treatment for Early Breast Cancer

Background: The role of adaptive immunity in long-term outcomes in early breast cancer is increasingly recognised. Standard (neo)adjuvant chemotherapy can have adverse effects on immune cells and the effect of contemporary chemotherapy regimens on long-term adaptive immune responses is not well described. Methods: A retrospective longitudinal study of serial peripheral full blood counts (FBC) of patients from a single institution receiving (neo)adjuvant chemotherapy for early breast cancer was conducted. Flow cytometric analysis was performed for nine patients with matched pre- and post-chemotherapy peripheral blood mononuclear cell (PBMC) samples. Results: FBC results at four timepoints spanning pre-treatment to 12 months post-treatment from 200 patients treated with (neo)adjuvant chemotherapy for early breast cancer were analyzed (62.5% hormone receptor-positive, HER-2 negative, 33% triple negative and 8% HER-2 positive). A significant decrease in absolute lymphocyte count (ALC) from baseline to 12 months post-chemotherapy was observed (p < 0.01), most pronounced in pre-menopausal patients (n=73; p < 0.01), patients receiving dose-dense chemotherapy regimens (n= 60; p < 0.01) and patients receiving adjuvant radiotherapy (n=147, p < 0.01). In premenopausal patients, a non-significant trend in the reduction of CD4+ naïve T cells and significant decreases in CD4+ T cells subsets post-chemotherapy were observed. Conclusion: (Neo)adjuvant chemotherapy significantly reduces peripheral lymphocyte count for at least 12 months, with CD4+ T subpopulations most affected. The clinical implications of these findings in the era of immunotherapy requires further investigation to inform optimum use of chemotherapy and radiotherapy in combination with immuno-oncology strategies.