Pre-treatment anxiety is associated with persistent chemotherapy-induced peripheral neuropathy in women treated with neoadjuvant chemotherapy for breast cancer

https://doi.org/10.1016/j.jpsychores.2018.02.012Get rights and content

Highlights

  • Approximately 20% women with breast cancer may experience persistent CIPN.

  • Pre-treatment anxiety is a risk factor for this condition.

  • Targeted interventions to manage anxiety before and during chemotherapy are needed.

Abstract

Objective

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse reaction caused by chemotherapeutic agents, especially the taxanes. CIPN can persist from months to years after completion of chemotherapy, decreasing quality of life for cancer survivors. The aim of this study was to explore the incidence and risk factors of persistent CIPN among women with breast cancer receiving neoadjuvant chemotherapy.

Methods

In this prospective study, we recruited women with breast cancer receiving neoadjuvant chemotherapy, including four cycles of docetaxel. Participants reported neuropathic symptoms of tingling/numbness at baseline, at the end of chemotherapy treatment, and at 8 months after completion of chemotherapy. Candidate factors associated with CIPN were assessed before chemotherapy.

Results

Among 111 participants, 50 (45.0%) experienced CIPN during chemotherapy, and 21 (18.9%) reported persistent CIPN after chemotherapy. Univariate logistic regression analysis revealed that development of CIPN was significantly associated with pre-treatment numbness (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.09–7.40; p = .033), and persistent CIPN was significantly associated with pre-treatment numbness (OR, 3.60; 95% CI, 1.12–11.61; p = .032) and pre-treatment anxiety (OR, 5.02; 95% CI, 1.84–13.70; p = .002). Multivariate analysis indicated that pre-treatment anxiety remained significantly associated with persistent CIPN (OR, 4.01; 95% CI, 1.25–12.87; p = .020).

Conclusion

Our results suggested that pre-treatment anxiety might be related to a patient's risk for persistent CIPN in women with breast cancer undergoing neoadjuvant chemotherapy. Further research is required to investigate if interventions targeting pre-treatment anxiety could provide prevention and management for persistent CIPN.

Introduction

Breast cancer is the most common cancer in women worldwide and the second most common cancer after thyroid cancer in Korea [1]. As a result of early detection and improved treatment strategies, survival rates have improved remarkably in most developed countries, with a 92% 5-year relative survival rate in Korea [2]. The increased number of breast cancer survivors highlights the need to focus on the persistent burden of the disease, especially related to cancer treatment, which has an enormous potential to impact quality of life.

Neoadjuvant chemotherapy with taxanes has been commonly recommended for locally advanced breast cancer in order to improve surgical outcomes and to increase the opportunity for breast-conserving intervention [3,4]. Peripheral neuropathy is one of the most frequent adverse reactions induced by chemotherapeutic agents, especially the taxanes [5]. Chemotherapy-induced peripheral neuropathy (CIPN) predominantly involves the sensory peripheral nervous system and leads to symptoms characterised by numbness, tingling, paresthesia and sensory loss [6]. The incidence of CIPN in patients receiving chemotherapy ranges from approximately 30 to 40% [7]. Importantly, CIPN can persist from months to years after completion of chemotherapy, causing significant distress and decreasing the quality of life for cancer survivors [5].

Demographic variables such as health status, obesity, and age are considered predisposing factors for occurrence and duration of CIPN [8,9]. In addition, the chemotherapeutic regimen, cumulative dose and pre-existing neuropathy (related to diabetes or alcohol consumption or idiopathic) were also suggested to increase the risk of developing CIPN [[10], [11], [12]]. However, the identification of which patients will develop CIPN is still rather controversial, and most of these previous studies refer to adjuvant chemotherapy, and not specifically to neoadjuvant chemotherapy [13,14]. Furthermore, we are not aware of other studies that have investigated psychiatric factors including anxiety, depression, and sleep disturbance as risk factors for CIPN. Considering that antidepressant agents, for example, duloxetine and amitriptyline, have been shown to be helpful for CIPN [[15], [16], [17]], it is necessary to explore which psychiatric factors in the pre-treatment period could be potentially associated with the development and persistence of CIPN.

Consequently, a prospective study with a standardised clinical assessment conducted for a 1-year period before, during, and after neoadjuvant chemotherapy may contribute to a better understanding of the pre-treatment factors associated with this neurological complication. The aim of this study was to explore the prevalence of CIPN in women with breast cancer receiving neoadjuvant chemotherapy and to identify these risk factors, including psychiatric factors that contribute to the development and persistence of CIPN.

Section snippets

Study design and setting

Participants were enrolled in this prospective observational study in a tertiary general hospital in Seoul, Korea, between November 2013 and March 2016. Participants were women with breast cancer, aged 18 to 70 years, and were enrolled while they awaited neoadjuvant chemotherapy. The participants' treatment plan consisted of four cycles of anthracyclines and cyclophosphamide, followed by additional four cycles of docetaxel. Patients were excluded if they had a history of another cancer or

Sample characteristics

We approached 328 patients scheduled to receive chemotherapy before surgery. Of these, 63 patients were ineligible (due to metastasis, 24; changed treatment plan, 9; psychiatric treatment, 9; shift work, 10; low literacy, 3; and other medical conditions, 8). Among the remaining 265 eligible participants, 122 patients declined to participate. Accordingly, 143 participants were included at baseline. Of these, 32 participants were excluded during the follow-up (due to loss to follow-up, 23;

Discussion

The objective of this study was to explore the incidence and risk factors associated with CIPN in breast cancer patients receiving neoadjuvant chemotherapy using docetaxel. Among the participants, 45% reported CIPN at the end of treatment. Among them, 42% reported persistent CIPN after discontinuation of treatment. These results seem to be consistent with previous studies that found that the incidence of docetaxel-induced peripheral neuropathy ranged from 11 to 64% in patients treated with

Declaration of interest statement

This work was supported by the National Research Foundation of Korea (NRF; grant number NRF-2013R1A1A2013480). The authors declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or the national research committee, as well as with the 1964 Helsinki Declaration and its later amendments and incorporating comparable ethical standards.

Conflict of interest

The authors have no competing interests to report.

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