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Chemobrain in Breast Cancer: Mechanisms, Clinical Manifestations, and Potential Interventions

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Abstract

Among the potential adverse effects of breast cancer treatment, chemotherapy-related cognitive impairment (CRCI) has gained increased attention in the past years. In this review, we provide an overview of the literature regarding CRCI in breast cancer, focusing on three main aspects. The first aspect relates to the molecular mechanisms linking individual drugs commonly used to treat breast cancer and CRCI, which include oxidative stress and inflammation, reduced neurogenesis, reduced levels of specific neurotransmitters, alterations in neuronal dendrites and spines, and impairment in myelin production. The second aspect is related to the clinical characteristics of CRCI in patients with breast cancer treated with different drug combinations. Data suggest the incidence rates of CRCI in breast cancer vary considerably, and may affect more than 50% of treated patients. Both chemotherapy regimens with or without anthracyclines have been associated with CRCI manifestations. While cross-sectional studies suggest the presence of symptoms up to 20 years after treatment, longitudinal studies confirm cognitive impairments lasting for at most 4 years after the end of chemotherapy. The third and final aspect is related to possible therapeutic interventions. Although there is still no standard of care to treat CRCI, several pharmacological and non-pharmacological approaches have shown interesting results. In summary, even if cognitive impairments derived from chemotherapy resolve with time, awareness of CRCI is crucial to provide patients with a better understanding of the syndrome and to offer them the best care directed at improving quality of life.

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Authors and Affiliations

  1. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil

    Giovana R. Onzi, Solange C. Garcia, Silvia S. Guterres & Adriana R. Pohlmann

  2. Programa de Pós-Graduação em Patologia da Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Nathalia D’Agustini & Daniela D. Rosa

  3. Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, USA

    Paula R. Pohlmann

  4. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Paula R. Pohlmann

  5. Serviço de Oncologia, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil

    Daniela D. Rosa

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Giovana R. Onzi received a research fellowship from the National Council for Scientific and Technological Development (CNPq #150654/2020-0). Adriana R. Pohlmann received a research grant from the National Council for Scientific and Technological Development (CNPq # 305343/2019-0). Silvia S. Guterres received a research grant and fellowship from FAPERGS (#18.2551.0000513-4).

Conflict of interest

Giovana R. Onzi works for Astrazeneca Brazil as a full-time employee. This manuscript was elaborated while the author was still working as a postdoctoral researcher at Federal University of Rio Grande do Sul. Paula R. Pohlmann has received consulting fees or honorarium from Perthera, Immunonet, Sirtex, CARIS, OncoPLex Diagnostics, Pfizer, Heron, Puma, BOLT, and Abbvie; fees for participation in review activities such as data monitoring boards from SEAGEN; payment for lectures including service on speakers bureaus from Dava Oncology, United Medical lecture, ION Oral Oncolytics Lecture, and Genentech/Roche; and holds stock/stock options in Immunonet. Daniela D. Rosa has received consulting fees or honorarium from Roche, Novartis, AstraZeneca, and Lilly; fees for participation in review activities such as data monitoring boards from Daiichi-Sankyo, Lilly, and Teva; and payment for lectures including service on speakers bureaus from Novartis, Pfizer, and AstraZeneca. Nathalia D’Agustini, Solange C. Garcia, Silvia S. Guterres, and Adriana R. Pohlmann have no conflicts of interest to declare.

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All authors participated in the conceptualization of the manuscript. Giovana R. Onzi and Nathalia D’Agustini wrote the manuscript. Giovana R. Onzi and Adriana R. Pohlmann performed the data curation and analysis. All authors reviewed the final manuscript. Silvia S. Guterres, Daniela D. Rosa, and Adriana R. Pohlmann supervised the work and were responsible for funding acquisition.

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Onzi, G.R., D’Agustini, N., Garcia, S.C. et al. Chemobrain in Breast Cancer: Mechanisms, Clinical Manifestations, and Potential Interventions. Drug Saf 45, 601–621 (2022). https://doi.org/10.1007/s40264-022-01182-3

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