Abstract

Abstract Background: Breast cancer-related lymphedema (BCRL) is encountered by approximately 40% of breast cancer survivors. BCRL drastically affects quality of life, as the arm, breast, and trunk swelling, together with pain, depression, and cellulitis risk can make everyday functions difficult or impossible. Objective: To identify plasma biomarkers that can suggest targeted pharmacological treatments for breast cancer survivors who develop lymphedema (LE). Methods: In a prospective, ongoing, longitudinal clinical study (NCT02949726), peripheral blood, perometric arm volumes, and near-infrared fluorescence lymphatic images/videos (NIRF-LI) for the first 33 enrolled advanced breast cancer patients were collected pre-mastectomy/breast-conserving surgery with ALND, four weeks postoperatively, at the end of radiation therapy (RT), and at 6 months post-RT. 29 cytokines were measured at each time point using a MILLIPLEX MAP human cytokine/chemokine magnetic bead panel from isolated blood plasma. Cytokine levels in subjects with >5% perometric arm swelling at 6 months post-regional nodal RT were analyzed and compared to those with <5% perometric arm swelling at 6 months post-regional nodal RT. Additionally, subjects who exhibited LE-associated dermal backflow, identified by cloudy fluid masses, instead of linear vessels, with NIRF-LI, at 6 months post-regional nodal RT were compared to those without backflow at 6 months post-regional nodal RT. GraphPad/Prism 9 non-parametric Mann-Whitney t-test was used to compute the p-values of each cytokine. P-values less than 0.05 were deemed significant. Results: Out of the 33 subjects, 7 developed >5% perometric arm swelling 6 months post-regional nodal RT and 15 developed dermal backflow 6 months post-regional nodal RT. Of the 15 subjects that developed backflow, 7 also had >5% perometric arm swelling. G-CSF, GM-CSF, IL-10, IL-12p40, and IL-1R-alpha were found to be significantly higher in subjects with >5% perometric arm swelling at 6 months post-RT than in subjects with <5% perometric arm swelling while IL-1beta was identified to be significantly lower in subjects with backflow at 6 months post-regional nodal RT than those without backflow at 6 months post-regional nodal RT. Conclusions: G-CSF, GM-CSF, IL-10, IL-12p40, IL-1Ralpha, and IL-1beta are candidate biomarkers for detecting and directing pharmacological treatment for lymphedema in breast cancer survivors. Citation Format: Anna R Vang, Simona F Shaitelman, Eva M Sevick-Muraca, Chan Wen-yaw, John C Rasmussen, Sarah D DeSnyder, Melissa B Aldrich. Plasma cytokine levels in breast cancer-related lymphedema patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-21.

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