Evaluating the impact of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) on perceived ability to work in breast cancer survivors during the first year post-treatment
- 1.5k Downloads
- 5 Citations
Abstract
Purpose
To describe the impact of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) on breast cancer survivors’ (BCS) perceived ability to work post-treatment.
Methods
The sample included 22 chemotherapy-treated (Ctx+) and 22 chemotherapy-naïve (Ctx−) female BCS. Data was collected at the following three time points: baseline (post-surgery, pre-chemotherapy), 1 month (1 M) post-chemotherapy, and approximately 1 year (1 Y) later. The presence, frequency, number, and severity of CIPN-sx were self-reported using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity questionnaire (FACT/GOG-Ntx) version 4, a validated 11-item CIPN measure. Perceived ability to work was measured using an item from the Functional Well-Being subscale of the FACT/GOG-Ntx.
Results
At 1 Y, more than 50 % of Ctx+ reported discomfort, numbness, or tingling in their hands or feet; weakness; or difficulty feeling small objects. The presence, number, and severity of these symptoms were correlated with being less able to work for Ctx+ at 1 M but not 1 Y. Results of a regression analysis using CIPN-sx to predict work ability found that models combining (1) hand numbness and trouble feeling small objects, (2) trouble buttoning buttons and trouble feeling small objects, (3) foot numbness and foot pain, (4) foot numbness and trouble walking, and (5) trouble hearing and hand pain each predicted survivors who were “not at all” able to work at 1 M.
Conclusions
Unresolved CIPN-sx may play a role in challenges working for BCS post-treatment. These findings highlight the need for research to explore the impact that CIPN-sx have on BCS’ ability to work, as well as the development of interventions to improve work function in BCS with CIPN-sx.
Keywords
Breast cancer Chemotherapy Peripheral neuropathy CIPN Survivorship Symptoms Work Perceived occupational functionAbbreviations
- 1 M
One-month time point, approximately 1 month post-chemotherapy treatment completion
- 1 Y
One year time point, approximately 1 year after 1-M time point
- BL
Baseline time point, post-surgery, pre-chemotherapy
- CIPN
Chemotherapy-induced peripheral neuropathy
- CIPN-sx
Chemotherapy-induced peripheral neuropathy symptoms
- Ctx+
Breast cancer patients who received chemotherapy during treatment
- Ctx−
Breast cancer patients who did not receive chemotherapy during treatment
- FACT/GOG-Ntx
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity questionnaire
Introduction
For the majority of adults in the U.S., work is an essential part of life. Breast cancer survivors (BCS) are no exception; an estimated 60–90 % of BCS return to work full-or part-time after completing cancer treatment [1, 2], and a growing number of BCS work throughout their cancer treatment as well [3, 4]. Beyond the simple economic necessity of working, for many survivors, work offers a vital source of self-esteem, structure, and social support [5]. Unfortunately, for many BCS, side effects related to their cancer treatments can interfere with their ability to return to work and regain pre-treatment levels of occupational function [6, 7, 8].
One side effect of cancer treatment that has received comparatively little attention in the discussion of work among BCS is chemotherapy-induced peripheral neuropathy (CIPN), a form of nerve damage associated with a number of commonly used cancer therapies. Current estimates suggest that 30 % or more of BCS receiving chemotherapy develop some degree of CIPN during treatment depending on the agents, regimen, and individual risk factors [9, 10]. While research has begun to illustrate the potentially serious impact that CIPN symptoms (CIPN-sx) can have on women’s quality of life [11, 12, 13], ability to complete treatment [14, 15], and ability to perform daily activities [16, 17], the impact of CIPN-sx on survivors’ ability to work is only beginning to be investigated.
This is troubling for several reasons. First, women make up nearly half of the U.S. labor force [18] and more than 99 % of cases of breast cancer in the U.S. [19]. In many of these cases, use of neurotoxic chemotherapy is standard, putting more and more BCS at risk for developing CIPN. Second, studies have shown that the majority of BCS resume work after treatment [20] but often with significant difficulty [21]. Issues ranging from fatigue, physical limitations, and cognitive symptoms have all been implicated in this difficulty returning to pre-treatment levels of occupational functioning [5, 20], but the role that CIPN-sx may play in this difficulty is unclear. This lack of clarity is particularly troubling because 23–86 % of BCS who develop CIPN-sx during treatment continue to report CIPN-sx after treatment [22, 23, 24, 25, 26, 27], when return to work is likely. Thirdly, while a number of studies have shown that the severity of CIPN-sx is associated with disruptions in treatment [14, 15], poorer quality of life [28], and greater use of health care resources [29], it is not clear whether the presence, frequency, severity, or total number of CIPN-sx is the best predictor of difficulty working post-treatment.
The purpose of this analysis was to evaluate the impact that the presence, frequency, number, and severity of CIPN-sx have on BCS’ perceived ability to work post-treatment. Specific aims were to (1) compare the presence, frequency, number, and severity of CIPN-sx in BCS exposed to chemotherapy (Ctx+) to BCS whose treatment did not include chemotherapy (Ctx−); (2) compare perceived ability to work between Ctx+ and Ctx− and determine whether the presence, severity, and total number of CIPN-sx survivors reported were associated with their ability to work during the first year post-treatment; and (3) explore which combinations of CIPN-sx best predict survivors’ ability to work post-treatment.
Methods
Sample and eligibility
Data for the analysis came from a recent longitudinal study evaluating the effect of cancer and cancer treatment on cognitive function in Ctx+ and Ctx− women with non-metastatic breast cancer (i.e., stages 0–IIIc). The original study also included demographically matched healthy controls, as previously described [30, 31, 32]. Healthy controls were not evaluated for CIPN-sx and, therefore, were not included in the analysis.
Participants were recruited from the Indiana University Melvin and Bren Simon Cancer Center’s recruitment core and affiliated clinical sites. Approval for the study was granted by the Indiana University Institutional Review Board. Written informed consent was collected from all participants. Data was collected at the following three time points: (1) baseline (after breast surgery but before radiation, chemotherapy, or anti-estrogen treatment), (2) approximately 1 month (1 M) after completing chemotherapy, and (3) approximately 1 year (1 Y) after the 1 M visit. Approximately one third of Ctx+ received neo-adjuvant chemotherapy and were surgery and treatment naïve at baseline.
The sample for this analysis consisted of 22 Ctx− and 22 Ctx+ women with non-metastatic breast cancer, ages 69 or younger. Exclusion criteria included a self-reported history of prior cancer; substance abuse; and other medical, neurological, and psychiatric risk factors with the potential to affect central or peripheral neurological structure/function [30, 31]. All Ctx+ women were treated with standard doses of chemotherapy agents known to cause CIPN-sx, such as taxanes and platinum compounds.
Measures
Demographics and cancer treatment
Age at baseline (years), education (years), race and ethnicity (categories), and initial stage of breast cancer (0–IIIc) were collected by self-report at baseline. Information on participants’ exposure to chemotherapy and other treatments associated with the development of symptoms simlar to CIPN-sx (e.g., muscle/joint pain) were collected from medical records.
Presence, frequency, number, and severity of CIPN-sx
The presence, frequency, number, and severity of CIPN-sx were measured using the neurotoxicity subscale of the Functional Assessment of Cancer Treatment Gynecological Oncology Group–Neurotoxicity questionnaire (FACT/GOG-Ntx) scale, version 4. The Ntx is an 11-item subscale of the FACT/GOG that measures the presence and severity of several common CIPN-sx. Items ask participants to rate the degree of sensory, motor, auditory, and functional CIPN-sx they experienced during the past week on a five-point Likert scale (0–4), corresponding with increasing symptom severity [33, 34]. The reliability and sensitivity of the Ntx subscale for assessing CIPN-sx has been established (Cronbach’s α = 0.64–0.86) [35], especially in patients receiving taxanes [34]. Three Ctx+ and four Ctx− included in the original study were excluded from the analysis because complete data on CIPN-sx or perceived ability to work was not available. Given the unique nature of each question, missing data was not imputed.
The presence of CIPN-sx was determined by calculating the total number of Ctx+ and Ctx− women who reported having a specific CIPN-sx, regardless of its severity (i.e., any score greater than 0). The frequency of CIPN-sx was determined by converting the total number of women who reported having each CIPN-sx at each time point into a percentage. The total number of CIPN-sx at each time point was calculated by tabulating the number of unique CIPN-sx participants reported at each time point, regardless of their severity. The severity of CIPN-sx was determined by calculating mean scores for the (a) total FACT/GOG-Ntx scale; (b) total scores for the sensory, motor, hearing, and functional domains; and (c) scores for individual symptoms in each domain at each time point.
Perceived ability to work and employment status
Participants’ perceived ability to work was measured using an item from the Functional Well-Being subscale of the FACT/GOG-Ntx (version 4), which asked participants to respond to the statement “I am able to work (including housework).” Perceived ability to work was scored on a five-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).
To help inform the discussion about the impact of CIPN-sx on occupational function, we also evaluated (1) the percentage of women that were working either full-or part-time at each time point, (2) the type of work in which they were engaged (unskilled, semi-skilled, skilled, managerial/clerical/official/sales, or professional/technical), and (3) any change in the type of work performed from baseline to 1 Y.
Statistical analyses
Analyses were performed using SPSS, version 23 (IBM Corporation). Descriptive statistics were used to tabulate the presence (yes/no) and frequency (%) of CIPN-sx at each time point. Pearson’s chi-squared tests were used to compare the frequency of categorical demographic variables and the frequency of CIPN-sx between groups at 1 M and 1 Y. For categorical variables with fewer than five observations, Fisher’s exact test was substituted. For categorical variables with fewer than five observations where order mattered (i.e., stage of cancer and perceived ability to work), Mantel-Hanzel chi-squared tests were used. Independent sample t-tests were used to compare continuous demographic variables, the number of CIPN-sx reported, and total FACT/GOG-Ntx scores. Differences in domain scores and individual items on the FACT/GOG-Ntx were compared using Mann-Whitney U tests, with a Benjamini-Hochberg correction to reduce the risk of type I errors due to multiple comparisons. Differences in ordinal responses to the work item between Ctx+ and Ctx− were compared using ordinal regression models, using cancer stage as a covariate. Spearman’s coefficients (R s ) were used to identify significant correlations between the presence, severity, and number of CIPN-sx and ability to work post-treatment.
Ordinal regression models were constructed to explore the combination of CIPN-sx that best predicted ability to work for Ctx+ at 1 M and 1 Y. Because of the small sample size, 1 M and 1 Y models were limited to two CIPN-sx apiece (i.e., one predictor variable per ∼10 observations). Only the severity of CIPN-sx was used in the analyses to minimize the potential to inflate significance levels because of variables with shared sources of variance. Final regression models were selected based on their statistical significance (p value) and explanatory value (pseudo r 2 value). Because of the sample size, models were also carefully screened for signs of overfitting (e.g., initial model fit <0.05, goodness of fit >0.05).
Results
Demographics
Sample characteristics
| Ctx+ | Ctx− | Significance | |
|---|---|---|---|
| Demographics | N = 22 | N = 22 | |
| Age at baseline (years, mean (SD)) | 49.68 (8.0) | 52.68 (9.3) | 0.256 |
| Race (%, Caucasian) | 77.3 | 86.4 | 0.349 |
| Education (years, mean (SD)) | 15.59 (2.8) | 15.27 (2.4) | 0.684 |
| Less than high school (<12 years, %) | 4.5 | 4.5 | – |
| High school (12 years, %) | 9.1 | 9.1 | – |
| Some college (13–15 years, %) | 36.4 | 27.3 | – |
| Four-year college (16 years, %) | 18.2 | 27.3 | – |
| More than four-year college (>16 years, %) | 31.8 | 27.3 | – |
| Cancer and cancer treatment | |||
| Stage of breast cancer at diagnosis (%, stages 0–3) | |||
| Stage 0 | 0.0 | 18.2 | |
| Stage 1 | 50.0 | 68.2 | 0.002 c |
| Stage 2 | 40.9 | 13.6 | |
| Stage 3 | 9.1 | 0.0 | |
| Chemotherapy | |||
| Adjuvant (%) | 68.2 | 0.0 | – |
| Neo-adjuvant (%) | 31.8 | 0.0 | – |
| Received chemotherapy (any type, %) | 100.0 | 0.0 | – |
| Received a single neurotoxic agent during treatment (%) | 95.5 | 0.0 | – |
| Received two or more neurotoxic agents during treatment (%) | 31.7 | 0.0 | – |
| Type of chemotherapy received | |||
| Taxane (%) | 95.5 | 0.0 | – |
| Docetaxel (%) | 54.5 | 0.0 | – |
| Paclitaxel (%) | 40.9 | 0.0 | – |
| Platinating agent (%) | 22.7 | 0.0 | – |
| Carboplatin (%) | 22.7 | 0.0 | – |
| Received both taxane and platinum (%) | 22.7 | 0.0 | – |
| Total exposure to neurotoxic chemotherapy (mg/m2, mean (SD)) | 1757.1 (1967.3) | 0.0 | – |
| Total exposure to a taxane (mg/m2, mean (SD)) | 911.1 (491.8) | 0.0 | – |
| Amount of paclitaxel (mg/m2) | 452.5 (727.6) | 0.0 | – |
| Amount of docetaxel (mg/m2) | 388.7 (376.9) | 0.0 | – |
| Amount of carboplatin (mg/m2) | 958.1 (1828.9) | 0.0 | |
| Radiotherapy | |||
| Received radiotherapy during treatment (%) | 81.8 | 59.1 | 0.099 |
| Amount of radiation per fraction (Gy, mean (SD)) | 2.07 (0.96) | 1.93 (0.80) | 0.717 |
| Hormonal therapies | |||
| Aromatase inhibitor (AI; %) | 27.2 | 45.5 | 0.510b |
| Selective estrogen receptor modulators (SERMs; %) | 22.7 | 36.4 | 0.210a |
| Biologic agents | |||
| Trastuzamab (%) | 22.7 | 0.0 | 0.048 b |
| Other agents associated with painful and/or CIPN-like symptoms | |||
| Biphosphanate (%) | 13.6 | 0.0 | 0.233b |
Table 1 also details participant’s exposure to cancer treatments associated with CIPN-sx or similar symptoms (e.g., muscle/joint pain). More than 95 % of Ctx+ received at least one neurotoxic agent during treatment, and almost a third received two neurotoxic agents. Of these, all but one received a taxane (docetaxel 54.5 %, paclitaxel 40.9 %). Mean taxane exposure was 911 ± 492 mg/m2. Five Ctx+ who received a taxane also received the platinum compound carboplatin. Mean platinum exposure among Ctx+ was 958.1 ± 1828.9 mg/m2.
Presence and frequency of CIPN-sx
Frequency and total number of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) at baseline, 1-month, and 1-year time points
| Frequency of CIPN-sxa | Baseline (pre-treatment) | One-month time pointb | One-year time pointc | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Ctx+ | Ctx− | Ctx+ | Ctx− | Ctx+ | Ctx− | ||||
| %a | %a | Significance | %a | %a | Significance | %a | %a | Significance | |
| Sensory symptoms | |||||||||
| Numbness/tingling in hands | 18.2 | 18.2 | 1.000e | 59.1 | 13.6 | 0.002 d | 63.6 | 13.6 | 0.001 d |
| Numbness/tingling in feet | 9.1 | 18.2 | 0.664e | 54.5 | 9.1 | 0.001 d | 57.1 | 18.2 | 0.008 d |
| Discomfort in hands | 13.6 | 22.7 | 0.698e | 54.5 | 18.2 | 0.012 d | 52.4 | 27.3 | 0.092 d |
| Discomfort in feet | 18.2 | 27.3 | 0.472d | 59.1 | 27.3 | 0.033 d | 59.1 | 45.5 | 0.365d |
| Motor symptoms | |||||||||
| Joint pain/muscle cramps | 50.0 | 50.0 | 1.000d | 68.2 | 72.7 | 0.741d | 72.7 | 71.4 | 0.924d |
| Feeling weak all over | 22.7 | 22.7 | 1.000d | 77.3 | 36.4 | 0.006 d | 59.1 | 22.7 | 0.014 d |
| Trouble walking | 18.2 | 36.4 | 0.176d | 36.4 | 54.5 | 0.226d | 38.1 | 59.1 | 0.169d |
| Auditory symptoms | |||||||||
| Trouble hearing | 18.2 | 40.9 | 0.099d | 27.3 | 45.5 | 0.210d | 27.3 | 54.5 | 0.066d |
| Ringing/buzzing in ears | 9.1 | 0.0 | 0.448e | 36.4 | 4.5 | 0.021 e | 33.3 | 4.5 | 0.046 e |
| Functional symptoms | |||||||||
| Trouble buttoning buttons | 9.1 | 0.0 | 0.448e | 31.8 | 0.0 | 0.009 e | 33.3 | 0.0 | 0.004 e |
| Trouble feeling the shape of small objects in hand | 9.1 | 27.7 | 0.412e | 54.5 | 31.8 | 0.128d | 31.8 | 27.3 | 0.741d |
| Total number of CIPN-sx | |||||||||
| Mean (SD) | 1.95 (2.4) | 2.59 (2.2) | 0.366f | 5.59 (3.5) | 3.14 (2.0) | 0.006 f | 5.18 (3.5) | 3.41 (2.3) | 0.049 f |
Severity of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) at baseline, 1-month, and 1-year time points
| Baseline (pre-treatment) | One-month time pointa | One-year time pointb | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FACT/GOG-Ntx item | Ctx+ | Ctx− | α c | Significance | Ctx+ | Ctx− | α c | Significance | Ctx+ | Ctx− | α c | Significance |
| Sensory symptoms | ||||||||||||
| Numbness/tingling in hands | 0.32 (0.9) | 0.27 (0.7) | 0.050 | 0.986 | 1.4 (1.5) | 0.27 (0.8) | 0.003 | 0.002 | 1.3 (1.4) | 0.27 (0.9) | 0.008 | 0.001 |
| Numbness/tingling in feet | 0.14 (0.5) | 0.41 (1.0) | 0.034 | 0.355 | 1.5 (1.6) | 0.09 (0.3) | 0.002 | 0.001 | 1.1 (1.4) | 0.41 (1.1) | 0.016 | 0.013 |
| Discomfort in hands | 0.27 (0.9) | 0.32 (0.7) | 0.037 | 0.473 | 1.2 (1.5) | 0.32 (0.7) | 0.012 | 0.012 | 0.95 (1.2) | 0.55 (1.0) | 0.043 | 0.142 |
| Discomfort in feet | 0.23 (0.5) | 0.50 (1.0) | 0.035 | 0.405 | 1.3 (1.5) | 0.59 (1.1) | 0.018 | 0.055 | 1.9 (1.3) | 1.1 (1.5) | 0.042 | 0.608 |
| Motor symptoms | ||||||||||||
| Joint pain or muscle cramps | 0.86 (1.1) | 0.91 (1.2) | 0.049 | 0.949 | 1.4 (1.4) | 1.3 (1.2) | 0.045 | 0.844 | 1.6 (1.3) | 1.6 (1.4) | 0.044 | 0.772 |
| Feel weak all over | 0.41 (0.9) | 0.27 (0.6) | 0.045 | 0.860 | 1.6 (1.5) | 0.45 (0.7) | 0.005 | 0.003 | 1.0 (1.1) | 0.4 (0.9) | 0.016 | 0.021 |
| Trouble walking | 0.27 (0.6) | 0.36 (0.5) | 0.030 | 0.277 | 0.68 (1.0) | 0.68 (0.7) | 0.040 | 0.550 | 0.67 (1.0) | 0.9 (0.9) | 0.031 | 0.296 |
| Auditory symptoms | ||||||||||||
| Trouble hearing | 0.41 (1.1) | 0.55 (0.7) | 0.024 | 0.152 | 0.59 (1.2) | 0.59 (0.7) | 0.032 | 0.338 | 0.55 (1.2) | 1.0 (1.0) | 0.019 | 0.071 |
| Ringing/buzzing in ears | 0.23 (0.8) | 0.00 (0.0) | 0.027 | 0.153 | 0.59 (1.0) | 0.05 (0.2) | 0.010 | 0.009 | 0.55 (0.9) | 0.05 (0.2) | 0.014 | 0.018 |
| Functional symptoms | ||||||||||||
| Trouble buttoning buttons | 0.23 (0.8) | 0.00 (0.0) | 0.026 | 0.153 | 0.55 (1.1) | 0.00 (0.0) | 0.006 | 0.004 | 0.55 (0.9) | 0.00 (0.0) | 0.004 | 0.002 |
| Trouble feeling the shape of small objects in hand | 0.32 (1.0) | 0.32 (0.7) | 0.034 | 0.352 | 0.64 (0.7) | 0.41 (0.7) | 0.022 | 0.141 | 0.45 (0.7) | 0.55 (1.1) | 0.048 | 0.895 |
| Total scores | ||||||||||||
| Sensory domain | 0.95 (2.4) | 1.5 (2.9) | 0.042 | 0.656 | 5.4 (5.6) | 1.3 (1.8) | 0.005 | 0.006 | 4.8 (3.9) | 2.3 (3.1) | 0.015 | 0.021 |
| Motor domain | 1.6 (2.7) | 1.5 (1.8) | 0.041 | 0.575 | 3.6 (3.0) | 2.1 (1.9) | 0.019 | 0.110 | 3.1 (2.8) | 2.5 (2.8) | 0.036 | 0.419 |
| Hearing domain | 0.68 (1.5) | 0.91 (1.0) | 0.021 | 0.127 | 1.3 (1.9) | 1.3 (1.3) | 0.036 | 0.524 | 1.2 (1.8) | 1.8 (1.8) | 0.028 | 0.157 |
| Functional domain | 0.45 (1.7) | 0.00 (0.0) | 0.025 | 0.153 | 1.1 (2.0) | 0.05 (0.2) | 0.009 | 0.007 | 1.1 (1.7) | 0.05 (0.2) | 0.006 | 0.004 |
| Total FACT-GOG/Ntx score | 3.7 (6.8) | 3.9 (4.1) | 0.047 | 0.894 | 11.4 (10.3) | 4.7 (3.4) | 0.017 | 0.034 | 9.9 (8.3) | 6.7 (5.5) | 0.022 | 0.148 |
Between 1 M and 1 Y, the frequency of some CIPN-sx increased slightly between for Ctx+. At 1 Y, a slightly higher percentage of Ctx+ reported hand numbness/tingling (63.6 vs. 59.1 %), foot numbness/tingling (57.1 vs. 54.5 %), joint pain/muscle cramps (72.7 vs. 68.2 %), trouble buttoning buttons (33.8 vs. 31.8 %), and difficulty walking (38.1 vs. 27.3 %) than at 1 M.
Total number of CIPN-sx
At 1 M, Ctx+ reported an average of 5.59 ± 3.5 CIPN-sx, compared to 3.14 ± 2.0 CIPN-sx for Ctx− (p = 0.006; Table 2). A year later, the total number of CIPN-sx Ctx+ reported was virtually unchanged; at 1 Y, Ctx+ reported an average of 5.18 ± 3.5 symptoms and Ctx− reported 3.41 ± 2.3 (p = 0.049).
Severity of CIPN-sx
At 1 M, Ctx+ reported significantly more severe functional CIPN-sx than Ctx− (p = 0.007). In addition, total scores on the sensory domain just missed the cutoff for statistical significance after adjusting for multiple comparisons (p = 0.006; Table 3). Inspection of individual FACT/GOG-Ntx scores revealed that Ctx+ had more severe numbness/tingling in their hands (p = 0.002) and feet (p = 0.001), hand discomfort (p = 0.012), weakness (p = 0.003), ringing/buzzing in their ears (p = 0.009), and trouble buttoning buttons (p = 0.004) than Ctx− after treatment.
At 1 Y, while total and sensory FACT-GOG/Ntx scores were not significantly different between Ctx+ and Ctx−, Ctx+ continued to report more severe functional CIPN-sx than Ctx− (p = 0.004), including more severe numbness/tingling in their hands (p = 0.001) and feet (p = 0.013) and trouble buttoning buttons (p = 0.002; Table 3).
Employment status and perceived ability to work
Employment status, type of work, and perceived ability to work at baseline, 1-month, and 1-year time points. The figure illustrates the percentages of Ctx+ and Ctx−, respectively, who were classified as working in each type of work (unskilled, semi-skilled, skilled, managerial/clerical/official, or professional/technical) at each time point (BL, 1 M, 1 Y)
Perceived ability to work at baseline, 1-month, and 1-year time points. The figure illustrates the percentage of Ctx+ and Ctx− who reported being not at all, a little bit, somewhat, quite a bit, and very much able to work (including housework) at each time point
Compared to survivors who reported being “very” able to work at 1 M, having received chemotherapy during treatment significantly predicted being only “somewhat” (p = 0.00), “a little bit” (p = 0.00), or “not at all” (p = 0.03) able to work, after controlling for differences in cancer stage between Ctx+ and Ctx− (data not shown). Similarly, at 1 Y compared to women who were very able to work, having received chemotherapy during treatment was also significantly associated with being only “a little” or somewhat able to work, after controlling for stage of cancer. This difference was especially evident at 1 M, where 50 % of Ctx+ reported being only somewhat, a little bit, or not at all able to work, compared to just 9.1 % of Ctx− survivors.
Association between presence, severity, and number of CIPN-sx and ability to work
At 1 M, the severity of the following five combinations of CIPN-sx were correlated with BCS’ work ability: hand numbness/tingling (R s = −0.483; p = 0.023), hand discomfort (R s = −0.511; p = 0.015), weakness (R s = −0.557; p = 0.007), trouble hearing (R s = −0.454; p = 0.034), and difficulty feeling the shape of small objects (R s = −0.463; p = 0.030). In addition, at 1 M the presence of any hand discomfort (R s = −0.455; p = 0.033), weakness (R s = −0.603; p = 0.003), trouble hearing (R s = −0.501; p = 0.018), or trouble feeling the shape of small objects in hand (R s = −0.433; p = 0.044), regardless of severity, were also significantly correlated with work scores among Ctx+, as was the number of CIPN-sx reported at 1 M (R s = −0.526; p = 0.012).
At 1 Y, only the presence of weakness (regardless of severity) was associated with perceived work ability for Ctx+ (R s = −0.478; p = 0.024).
Using the severity of CIPN-sx to predict work ability post-treatment
Ordinal regression models using the severity of CIPN-sx to predict perceived work ability in chemotherapy-treated (Ctx+) breast cancer survivors approximately 1 month after treatment (N = 22)
| Variable (reference) | Coefficient | SE | Wald | p value | 95 % CI | Cumulative odds ratio | Nagelkerke r 2 | |
|---|---|---|---|---|---|---|---|---|
| Lower | Upper | |||||||
| Combination 1, hand symptoms | ||||||||
| Ability to work (not at all) | −4.24 | 1.26 | 11.39 | 0.001 | −6.70 | −1.78 | 0.008 | 0.500 |
| Hand numbness (somewhat) | −4.50 | 1.89 | 5.64 | 0.018 | −8.21 | −.786 | ||
| Trouble feeling the shape of small objects (very much) | 7.28 | 3.13 | 5.43 | 0.020 | 1.16 | 13.41 | ||
| Combination 2, hand symptoms | ||||||||
| Ability to work (not at all) | −5.50 | 1.53 | 12.99 | 0.000 | −8.50 | −2.51 | 0.004 | 0.567 |
| Trouble buttoning buttons (a little bit) | −3.79 | 1.60 | 5.60 | 0.018 | −6.93 | −0.65 | ||
| Trouble feeling the shape of small objects (somewhat) | −4.48 | 1.87 | 5.75 | 0.017 | −8.15 | −0.82 | ||
| Combination 3, lower extremity | ||||||||
| Ability to work (not at all) | −3.47 | 1.26 | 7.65 | 0.006 | −5.94 | −1.01 | 0.031 | 0.644 |
| Foot numbness (somewhat) | −5.98 | 2.36 | 6.40 | 0.011 | −10.6 | −1.35 | ||
| Foot pain (quite a bit) | 9.36 | 4.21 | 4.95 | 0.026 | 1.12 | 17.60 | ||
| Combination 4, lower extremity | ||||||||
| Ability to work (not at all) | −5.79 | 1.77 | 10.67 | 0.001 | −9.26 | −2.32 | 0.003 | 0.724 |
| Foot numbness (quite a bit) | −4.68 | 1.83 | 6.52 | 0.011 | −8.28 | −1.09 | ||
| Trouble walking (quite a bit) | 4.40 | 2.12 | 4.33 | 0.037 | 0.26 | 8.55 | ||
| Combination 5, hearing and hand pain | ||||||||
| Ability to work (not at all) | −5.32 | 1.54 | 12.02 | 0.001 | −8.33 | −2.31 | 0.005 | 0.583 |
| Hand pain (very much) | −3.94 | 1.72 | 5.26 | 0.022 | −7.32 | −0.57 | ||
| Trouble hearing (a little bit) | −4.31 | 1.85 | 5.45 | 0.020 | −7.94 | −0.69 | ||
Discussion
There is growing evidence that CIPN-sx pose a risk to BCS not only during cancer treatment but after as well [24, 25, 26, 36, 37, 38, 39, 40, 41]. Previous research has linked CIPN-sx with poorer quality of life and decreased ability to function [28], but this is one of the first studies to address the question of whether CIPN-sx impact work in BCS post-treatment [28]. Results of this study add to the growing evidence showing the persistence of CIPN-sx after treatment [25, 26, 36], and extend these findings to the context of occupational function, demonstrating a clear link between the presence, frequency, number, and severity of CIPN-sx and BCS’ self-reported inability to work following treatment. Results of our analysis also suggest that (1) the total number of CIPN-sx Ctx+ report, regardless of their severity, may be a useful predictor of difficulty working and that (2) painful and non-painful CIPN-sx affecting the hands or feet (with or without treatment-related hearing deficits) may predict work difficulty for Ctx+ 1 M post-treatment.
Presence and frequency of CIPN-sx
An important finding from our analysis was that the pattern of CIPN-sx reported by Ctx+ approximately a year post-treatment was very similar to the pattern reported at 1 M. In the context of work, this has important implications because it raises the possibility that the CIPN-sx survivors present with immediately after treatment may be a reliable indicator of the CIPN-sx that will continue to interfere with a survivor’s ability to work during the critical first year of survivorship. Research in larger samples is needed to test this hypothesis.
Total number of CIPN-sx
A second potentially important finding from our analysis was that the number of CIPN-sx Ctx+ reported, independent of their severity, appeared to predict ability to work post-treatment. The majority of studies have used either the presence [14, 15, 29] or severity of CIPN-sx as the primary lens for evaluating CIPN-related outcomes [41]. While our results suggest that both are likely to predict work ability, the number of CIPN-sx patient’s experience itself may also be disruptive to work. On average, Ctx+ in our sample reported five different CIPN-sx at both post-treatment time points. As with other studies, when we looked at the severity of these CIPN-sx, in many cases, we observed a pattern of one or two severe CIPN-sx and several milder symptoms [41]. Because this mixed severity pattern is common, it will be important to clarify whether the number of CIPN-sx survivors report is just as predictive of difficulty working as severity of each symptom. This is not only because the severity of CIPN-sx can vary but also because CIPN-sx often grow less severe over time [10], which could lead providers to overlook the potentially serious impact that a number of milder CIPN-sx could have on BCS’ ability to work.
Association between the severity of CIPN-sx and ability to work at 1 M
During our regression analyses, we identified several combinations of CIPN-sx that were predictive of Ctx+ that were less able to work at 1 M. These included two combinations of sensory CIPN-sx affecting the hands, two combinations of CIPN-sx affecting the feet, and the combination of hearing loss and hand discomfort (Table 4). These findings are consistent with the few studies of CIPN in which work was considered [28] and make sense intuitively. In particular, the finding that sensory symptoms that interfere with women’s ability to feel the shape of objects or button buttons were associated with difficulty working was not surprising. These combinations of CIPN-sx point to potential phenotypes for CIPN-related work interference. It is important to note that several other symptoms such as weakness and joint pain/muscle soreness also predicted inability to work at 1 M in several of our models but were not included because of lack of model fit given our sample size. Statistical considerations notwithstanding, it is clear that symptoms such as joint pain/muscle soreness and weakness have the potential to impact work and should be included in future studies of CIPN-sx and work.
Association between the severity of CIPN-sx and ability to work at 1 Y
There are several reasons that may explain why we did not observe a stronger effect of CIPN-sx on perceived work ability at 1 Y. First, the percentage of Ctx+ who reported being “very much” or “quite a bit” able to work after treatment rose from 41.4 % at 1 M to 90.9 % at 1 Y (Fig. 2a). At the same time, the type, frequency, severity, and number of CIPN-sx Ctx+ reported remained relatively constant. This combination of improving ability to work in the face of relatively stable CIPN-sx suggests that while BCS may continue to experience CIPN post-treatment, the impact of these symptoms on work may lessen over time as BCS acclimate to their symptoms and/or develop coping strategies.
Finally, it is important to note that while the lack of treatments for CIPN-sx is problematic on many fronts, it is particularly concerning in the context of work. Recently, several groups have had some success treating the painful component of CIPN-sx non-invasively using devices such as scrambler therapy [42], as well as several oral or topical agents [10]. These successes raise the question of whether strategies like these could be used to address painful CIPN-sx before they can disrupt cancer survivors’ transition back to usual work activities.
Limitations
While this study provides a useful starting point for future research exploring the impact of CIPN-sx on breast cancer survivor’s ability to work post-treatment, our results need to be considered in light of several limitations. First, the sample for this analysis was small; larger samples will be needed to validate these findings and explore which combinations of CIPN-sx best predict survivor’s ability to work. Secondly, we did not have access to detailed information on potential risk factors for CIPN such as osteoarthritis, and the size of our sample prevented us from including symptoms such as depression as covariates in our analysis, both of which should be included in future studies. Third, our analysis relied on a single item to evaluate perceived ability to work post-treatment. While this item provided a useful lens for looking at the impact of CIPN-sx on work, clearly, more stringent and varied measures of work including absenteeism, productivity, and performance on job-specific tasks will be needed to understand the occupational impact of CIPN-sx. In addition, we did not have access to objective measures of CIPN, which would have provided valuable insight into structural or functional changes in nerves that may help to explain perceived difficulties working. Fourth, our sample was racially/ethnically homogeneous; more diverse cohorts will be needed to understand whether the impact of CIPN-sx on work outcomes differs by race, ethnicity, or culture. Finally, our sample was approximately 10 years younger than the median age of BCS in the USA. The reason for this was that the study upon which our analysis was based enrolled only women younger than age 70. As such, while our sample is representative of working-age BCS, studies in older survivors that continue work past the current typical age of retirement will be needed to explore the impact of CIPN-sx on work in this population fully.
Conclusion
The increasing reliance on neurotoxic chemotherapy to treat many forms of breast cancer means that clinicians and patients will need to carefully consider how best to balance the benefits and risks of treatment, including the potential impact of CIPN-sx on their ability to work. Our findings suggest that clinicians should remain vigilant for CIPN-sx that may interfere with women’s ability to work during the first year post-treatment, when many survivors return to work. Women who continue to experience CIPN-sx post-treatment (especially in the context of other symptoms that can interfere with work such as pain, fatigue, or cognitive disruption) may need to be referred to physical or occupational therapy to minimize the negative impact of CIPN-sx on work.
This concern may be especially pertinent in the modern workplace, with its growing reliance on tactile technologies such as keyboards and touch screens, which require users to be able to effortlessly tap, touch, type, and glide their way through their workday. Identifying the specific CIPN-sx and dimension of the symptom experience (i.e., presence, frequency, severity, or total number) that best predict difficulty working is an essential first step towards developing interventions to reduce their impact on work for BCS with CIPN.
Notes
Acknowledgments
This study was partially supported by the National Cancer Institute (R01 CA101318, R01 CA087845, P30 CA082709, and R25 CA117865) and the Indiana CTSI (UL1 RR025761, S10 RR027710, and C06 RR020128) with additional support from the National Institute on Aging (R01 AG019771, P30 AG010133). The authors thank the Indiana University Melvin and Bren Simon Cancer Center recruitment core and our oncologist colleagues for their invaluable assistance with patient recruitment. Finally, we are grateful to our participants for their time and effort; this research would not have been possible without their willingness to participate during a particularly challenging time in their lives.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose. The authors verify that they have full control of all primary data and agree, if requested, to allow the journal to verify the data from which all analyses were derived.
References
- 1.Islam T et al. (2014) Factors associated with return to work of breast cancer survivors: a systematic review. BMC Public Health 14(Suppl 3):S8CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Spelten ER, Sprangers MA, Verbeek JH (2002) Factors reported to influence the return to work of cancer survivors: a literature review. Psychooncology 11(2):124–131CrossRefPubMedGoogle Scholar
- 3.Tamminga SJ et al. (2012) Breast cancer survivors’ views of factors that influence the return-to-work process—a qualitative study. Scand J Work Environ Health 38(2):144–154CrossRefPubMedGoogle Scholar
- 4.Ahn E et al. (2009) Impact of breast cancer diagnosis and treatment on work-related life and factors affecting them. Breast Cancer Res Treat 116(3):609–616CrossRefPubMedGoogle Scholar
- 5.Banning M (2011) Employment and breast cancer: a meta-ethnography. Eur J Cancer Care (Engl) 20(6):708–719CrossRefGoogle Scholar
- 6.Bradley CJ et al. (2005) Short-term effects of breast cancer on labor market attachment: results from a longitudinal study. J Health Econ 24(1):137–160CrossRefPubMedGoogle Scholar
- 7.Mahon, S.M., et al. (2011) Breast cancer, in Site specific series, S.M. Mohan, Editor. Oncology Nursing Society. 248Google Scholar
- 8.de Boer, A.G., et al. (2011) Interventions to enhance return-to-work for cancer patients. Cochrane Database Syst Rev (2): p. CD007569Google Scholar
- 9.Wolf SL et al. (2012) The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer 20(3):625–632CrossRefPubMedGoogle Scholar
- 10.Hershman DL et al. (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32(18):1941–1967CrossRefPubMedGoogle Scholar
- 11.Mols, F., et al. (2014) Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care CancerGoogle Scholar
- 12.Driessen CM et al. (2012) Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the quality of life of cancer patients: the introduction of a new measure. Support Care Cancer 20(4):877–881CrossRefPubMedGoogle Scholar
- 13.Sorbe B et al. (2012) A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: neurological toxicity and quality-of-life evaluation. Int J Oncol 40(3):773–781PubMedGoogle Scholar
- 14.Bhatnagar B et al. (2014) Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: a single-center experience. Springerplus 3:366CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Speck RM et al. (2013) Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. J Oncol Pract 9(5):e234–e240CrossRefPubMedGoogle Scholar
- 16.Dougherty PM et al. (2004) Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain 109(1–2):132–142CrossRefPubMedGoogle Scholar
- 17.Tofthagen C (2010) Patient perceptions associated with chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs 14(3):E22–E28CrossRefPubMedGoogle Scholar
- 18.United States Department of Labor ( 2016) Labor force by sex, 2014 and projected 2022. [cited 2016 April 25]; Available from: http://www.dol.gov/wb/stats/laborforce_sex_projected_2014_2022_txt.htm
- 19.American Cancer Society (2016) Facts and figures, A.C. Society, Editor. AtlantaGoogle Scholar
- 20.Bradley CJ et al. (2007) Employment and cancer: findings from a longitudinal study of breast and prostate cancer survivors. Cancer Investig 25(1):47–54CrossRefGoogle Scholar
- 21.Chirikos TN, Russell-Jacobs A, Jacobsen PB (2002) Functional impairment and the economic consequences of female breast cancer. Women Health 36(1):1–20CrossRefPubMedGoogle Scholar
- 22.Forsyth PA et al. (1997) Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neuro-Oncol 35(1):47–53CrossRefGoogle Scholar
- 23.Park, S.B., et al. (2013) Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J ClinGoogle Scholar
- 24.Osmani K et al. (2012) Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation. J Neurol 259(9):1936–1943CrossRefPubMedGoogle Scholar
- 25.Pignata S et al. (2006) Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in ovarian cancer (MITO-4) retrospective study. BMC Cancer 6:5CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Hershman DL et al. (2011) Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat 125(3):767–774CrossRefPubMedGoogle Scholar
- 27.Smith, E.M., et al. (2013) Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial, in JAMA. United States. 1359–67Google Scholar
- 28.Tanay, M.A., J. Armes, and E. Ream (2016) The experience of chemotherapy-induced peripheral neuropathy in adult cancer patients: a qualitative thematic synthesis. Eur J Cancer Care (Engl)Google Scholar
- 29.Pike CT et al. (2012) Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract 2012:913848PubMedPubMedCentralGoogle Scholar
- 30.Nudelman KN et al. (2014) Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion. PLoS One 9(5):e96713CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Nudelman KN et al. (2016) Cerebral perfusion and gray matter changes associated with chemotherapy-induced peripheral neuropathy. J Clin Oncol 34(7):677–683CrossRefPubMedGoogle Scholar
- 32.McDonald BC et al. (2013) Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: a replication and extension study. Brain Behav Immun 30(Suppl):S117–S125CrossRefPubMedGoogle Scholar
- 33.Smith, E.M. (2013) Current methods for the assessment and management of taxane-related neuropathy, in Clin J Oncol Nurs. United States. 22–34Google Scholar
- 34.Huang HQ et al. (2007) Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer 17(2):387–393CrossRefPubMedGoogle Scholar
- 35.Griffith KA et al. (2010) Measures of chemotherapy-induced peripheral neuropathy: a systematic review of psychometric properties. J Peripher Nerv Syst 15(4):314–325CrossRefPubMedGoogle Scholar
- 36.Beijers A et al. (2014) Chemotherapy-induced peripheral neuropathy and impact on quality of life 6 months after treatment with chemotherapy. J Community Support Oncol 12(11):401–406CrossRefPubMedGoogle Scholar
- 37.Park SB et al. (2011) Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist 16(5):708–716CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Calhoun EA et al. (2003) Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 13(6):741–748CrossRefPubMedGoogle Scholar
- 39.Kuroi K et al. (2009) Prospective assessment of chemotherapy-induced peripheral neuropathy due to weekly paclitaxel in patients with advanced or metastatic breast cancer (CSP-HOR 02 study). Support Care Cancer 17(8):1071–1080CrossRefPubMedGoogle Scholar
- 40.Argyriou AA et al. (2005) Paclitaxel plus carboplatin-induced peripheral neuropathy. A prospective clinical and electrophysiological study in patients suffering from solid malignancies. J Neurol 252(12):1459–1464CrossRefPubMedGoogle Scholar
- 41.Bakitas, M.A. (2007) Background noise: the experience of chemotherapy-induced peripheral neuropathy, in Nurs Res. United States. 323–31Google Scholar
- 42.Marineo G et al. (2012) Scrambler therapy may relieve chronic neuropathic pain more effectively than guideline-based drug management: results of a pilot, randomized, controlled trial. J Pain Symptom Manag 43(1):87–95CrossRefGoogle Scholar
Copyright information
Open Access This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.