The quality of life for many cancer survivors is compromised due to severe, long-lasting side effects of chemotherapy. As part of a preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer, we examined the change in protein expression levels in blood collected from patients after treatment with taxanes for 12 weeks (n=7). Protein expression levels were measured with reverse-phase proteomic arrays. Here, we examine changes in proteins related to apoptosis, senescence, and calcium signaling in adjuvant vs. neoadjuvant-treated patients The largest change identified was BCL2 (B-cell lymphoma 2), a founding member of the BCL2 family of proteins that regulate apoptosis. Other proteins regulated by BCL2, including RB1 (retinoblastoma protein 1) and NLRP3 (NLR family pyrin domain containing 3) changed significantly over the course of treatment. These differences are relevant to calcium signaling dysregulation and an increased senescent response, both contributors to cancer recurrence. To validate the observations in this small sample, comparisons were made using Kaplan-Meier plots generated from The Cancer Proteome Atlas (TCPA) breast cancer data. The analysis of the TCPA data also shows a large population with upregulation of BCL2 and that elevated BCL2 is associated with a lower survival probability. Once further validated, these findings indicate that the long-term regulation of BCL2 and related proteins should be considered to optimize patient health and prevent recurrence after taxane-based treatment for breast cancer patients.

BEE is a founder and shareholder of Osmol Therapeutics, a company that is targeting NCS1 for therapeutic purposes. ML has served as consultant to Osmol Therapeutics. All the remaining authors declare no competing interest.

The work was supported by a grant from Hesi Thrive. LMF supported in part by a grant from the Breast Cancer Research Foundation (BCRF-22-184, PI: Winer). RLR is supported by Hyundai Hope on Wheels Young Investigator Award and the COVID-19 Fund to Retain Clinical Scientists at Yale, sponsored by the Doris Duke Charitable Foundation award # 2021266, and the Yale Center for Clinical Investigation.

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Studies were approved by the Yale Cancer Center Human Research Ethics Committee (NCT03872141) and written informed consent was obtained in accordance with the Declaration of Helsinki.

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Address for contact: Barbara E. Ehrlich, Department of Pharmacology, 333 Cedar Street, Yale School of Medicine, New Haven, CT 06520-8066, barbara.ehrlichyale.edu