Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Participants
2.2. Measures
2.3. Statistical Analysis
3. Results
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics, Cognitive Status, and Cytokine Levels | Pre-C/T | Post-C/T | Non-Cancer | ANOVA | ||
---|---|---|---|---|---|---|
Cancer Patients | Cancer Patients | Controls | ||||
(N = 70) | (N = 36) | (N = 30) | ||||
Basic Information | Mean (SD) | Mean (SD) | Mean (SD) | p | η2 | Post Hoc Tests ‡ |
Age (years) | 51.74 (11.39) | 49.97 (10.04) | 48.13 (11.30) | 0.312 | 0.017 | |
BMI | 24.14 (3.73) | 24.42 (4.15) | 24.77 (3.00) | 0.738 | 0.005 | |
Education (years) | 11.01 (4.46) | 11.97 (3.82) | 12.50 (3.97) | 0.220 | 0.023 | |
IQ † | 100.00 (11.37) | 101.14 (13.66) | 106.60 (10.43) | 0.039 * | 0.049 | control > pre-C/T |
PHQ-9 | 5.14 (4.42) | 4.06 (3.91) | 2.07 (2.56) | 0.002 * | 0.088 | pre-C/T > control |
HADS-A | 4.21 (3.71) | 2.44 (2.56) | 1.97 (2.68) | 0.002 * | 0.090 | pre-C/T > control |
BFI—fatigue severity score | 1.43 (2.29) | 2.26 (2.14) | 2.29 (2.62) | 0.108 | 0.033 | |
BFI—fatigue interference score | 4.04 (6.23) | 4.94 (8.04) | 0.68 (1.36) | 0.014 * | 0.063 | pre-C/T > control post-C/T > control |
N (%) | N (%) | N (%) | ||||
Menopausal status (No) | 37 (52.9) | 36 (100) | 14 (46.7) | <0.001 | ||
Stage | 0.823 | |||||
Stage I | 21 (30.00) | 12 (30.00) | - | |||
Stage II | 36 (51.43) | 16 (44.44) | - | |||
Stage III | 12 (17.14) | 7 (19.44) | - | |||
Treatment | ||||||
Mastectomy | 17 (24.64) | 33 (94.29) | - | |||
Time from Mastectomy to recruitment, days, Mean (SD) | 93.53 (181.55) | 288.43 (56.84) | ||||
Radiotherapy | 1 (1.43) | 30 (83.33) | - | |||
Hormonal therapy | 3 (4.29) | 28 (77.78) | - | |||
Targeted therapy | 0 | 0 | - | |||
Chemotherapy regimen | ||||||
Cyclophosphamide, 5-fluorouracil, epirubicin and doxorubicin, and docetaxel | - | 15 (50.00) | - | |||
Cyclophosphamide, 5-fluorouracil, epirubicin and doxorubicin, docetaxel, and cisplatin | - | 4 (13.33) | - | |||
Cyclophosphamide, 5-fluorouracil, epirubicin and doxorubicin | - | 4 (13.33) | - | |||
Cyclophosphamide, methotrexate, and 5-fluorouracil | - | 3 (1.00) | - | |||
Cyclophosphamide, methotrexate, epirubicin and doxorubicin | - | 1 (0.03) | - | |||
Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) | 119.26 (10.54) | 118.58 (10.11) | 116.13 (16.25) | 0.485 | 0.011 | |
Perceived Cognitive Impairment | 66.03 (6.41) | 65.83 (6.25) | 64.50 (9.70) | 0.615 | 0.007 | |
Comments from Others | 15.71 (0.89) | 15.56 (0.81) | 15.27 (1.82) | 0.201 | 0.024 | |
Perceived Cognitive Abilities | 22.13 (3.73) | 21.81 (3.48) | 21.30 (4.79) | 0.624 | 0.007 | |
Impact of Perceived Cognitive Impairments on Quality of Life | 15.39 (1.96) | 15.39 (1.42) | 15.07 (2.16) | 0.714 | 0.005 | |
Cytokines | ||||||
Th1 | ||||||
IFNγ | 6.35 (5.68) | 6.72 (4.62) | 12.45 (7.32) | <0.001 * | 0.156 | control > pre-C/T control > post-C/T |
IL-12p70 | 1.90 (1.56) | 1.93 (1.42) | 3.25 (2.00) | 0.001 | 0.016 | control > pre-C/T control > post-C/T |
IL-1β | 0.74 (0.81) | 0.64 (0.49) | 0.95 (0.50) | 0.175 | 0.026 | |
IL-2 | 1.29 (1.10) | 0.96 (0.80) | 1.66 (1.29) | 0.036 * | 0.049 | control > post-C/T |
TNF | 4.38 (2.55) | 4.99 (2.58) | 5.61 (2.83) | 0.093 | 0.035 | |
Th2 | ||||||
IL-4 | 10.09 (11.11) | 14.75 (22.05) | 18.62 (18.01) | 0.047 | 0.045 | |
IL-5 | 1.53 (1.22) | 1.16 (0.95) | 1.70 (1.18) | 0.134 | 0.030 | |
IL-10 | 4.64 (3.83) | 3.45 (3.34) | 6.28 (4.83) | 0.016 * | 0.060 | control > post-C/T |
IL-13 | 2.56 (2.71) | 2.84 (4.03) | 4.68 (2.72) | 0.008 * | 0.071 | control > pre-C/T |
Th17 | ||||||
IL-6 | 1.43 (1.68) | 1.63 (1.88) | 2.33 (1.69) | 0.060 | 0.041 | |
IL-17A | 5.40 (3.97) | 4.87 (2.65) | 7.70 (3.93) | 0.004 * | 0.078 | control > pre-C/T control > post-C/T |
Characteristics and Log Transformed Values of Cytokines | Pre-C/T | Post-C/T | Non-Cancer | ANCOVA | ||
---|---|---|---|---|---|---|
Cancer Patients | Cancer Patients | Controls | ||||
(N = 68) | (N = 35) | (N = 30) | ||||
Mean (SD) | Mean (SD) | Mean (SD) | F | η2 | p | |
IQ † | 100.00 (11.37) | 101.14 (13.66) | 106.60 (10.43) | 2.907 | 0.048 | 0.059 |
PHQ-9 | 5.01 (4.40) | 3.66 (3.13) | 2.07 (2.56) | 5.399 | 0.085 | 0.054 |
HADS-A | 4.21 (3.74) | 2.37 (2.56) | 1.97 (2.68) | 4.84 | 0.077 | 0.010 * Pre-C/T > control |
BFI—fatigue severity score | 1.38 (2.24) | 2.18 (2.12) | 2.29 (2.62) | 8.165 | 0.123 | <0.001 Pre-C/T < control Pre-C/T < post-C/T |
BFI—fatigue interference score | 4.04 (6.23) | 4.94 (8.04) | 0.68 (1.36) | 3.352 | 0.055 | 0.038 Post-C/T >control |
Cytokines | ||||||
Log_IFNr | 0.59 (0.47) | 0.67 (0.43) | 1.01 (0.31) | 3.052 | 0.048 | 0.046 * pre C/T < non-cancer |
Log_IL-2 | −0.01 (3.42) | −0.20 (0.43) | 0.09 (0.40) | 2.612 | 0.041 | 0.078 |
Log_TNFα | 0.57 (0.25) | 0.65 (0.19) | 0.71 (0.18) | 1.012 | 0.017 | 0.367 |
Log_IL-4 | 0.78 (0.43) | 0.93 (0.45) | 1.12 (0.37) | 3.193 | 0.051 | 0.045 |
Log_IL-12 | 0.13 (0.39) | 0.11 (0.45) | 0.41 (0.34) | 0.543 | 0.009 | 0.582 |
Log_IL-10 | 0.51 (0.40) | 0.31 (0.50) | 0.61 (0.48) | 2.609 | 0.042 | 0.078 |
Log_IL-13 | 0.15 (0.54) | 0.10 (0.67) | 0.57 (0.35) | 2.123 | 0.034 | 0.124 |
Subjective and Objective Cognitive Assessments | Pre-C/T Cancer Patients (N = 68) | Post-C/T Cancer Patients (N = 35) | Non-Cancer Controls (N =30) | ANOVA | ||
---|---|---|---|---|---|---|
Mean (SE) | Mean (SE) | Mean (SE) | p | η2 | Post Hoc Tests ‡ | |
Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) | 119.26 (10.54) | 118.58 (10.11) | 116.13 (16.25) | 0.485 | 0.011 | |
Perceived Cognitive Impairment | 66.03 (6.41) | 65.83 (6.25) | 64.50 (9.70) | 0.615 | 0.007 | |
Comments from Others | 15.71 (0.89) | 15.56 (0.81) | 15.27 (1.82) | 0.201 | 0.024 | |
Perceived Cognitive Abilities | 22.13 (3.73) | 21.81 (3.48) | 21.30 (4.79) | 0.624 | 0.007 | |
Impact of Perceived Cognitive Impairments on Quality of Life | 15.39 (1.96) | 15.39 (1.42) | 15.07 (2.16) | 0.714 | 0.005 | |
Attention function | ||||||
Digit Span | 11.25 (2.97) | 11.02 (3.38) | 12.01 (2.92) | 0.393 | 0.014 | |
Color Trails Test 1 | 51.52 (19.99) | 49.26 (22.89) | 47.27 (19.05) | 0.623 | 0.007 | |
Executive function | ||||||
Semantic Association of Verbal Fluency | 38.91 (8.22) | 37.33 (8.65) | 44.43 (8.22) | 0.002 * | 0.090 | Control > pre-C/T Control > post-C/T |
Orthographical Fluency Test | 17.59 (7.71) | 17.60 (7.82) | 20.44 (5.84) | 0.178 | 0.026 | |
Color Trails Test 2 | 98.20 (34.75) | 98.84 (35.08) | 88.67 (29.77) | 0.380 | 0.014 | |
Memory function | ||||||
Word List—Total immediate recall | 9.94 (2.50) | 9.67 (2.77) | 10.93 (2.94) | 0.132 | 0.030 | |
Word List—Long-delay recall | 10.59 (2.55) | 10.61 (2.53) | 10.97 (2.68) | 0.782 | 0.004 | |
Word List—Recognition | 11.07 (2.39) | 11.44 (2.27) | 11.23 (2.21) | 0.734 | 0.005 | |
Visuospatial construction | ||||||
Block Design | 9.33 (3.00) | 8.75 (3.38) | 9.67 (3.20) | 0.480 | 0.011 | |
Processing speed | ||||||
Digit Symbol Substitution | 10.26 (2.73) | 10.36 (2.66) | 11.13 (2.93) | 0.335 | 0.016 | |
Prospective memory | ||||||
Event-based | 4.07 (1.32) | 3.87 (0.32) | 3.87 (0.43) | 0.487 | 0.011 | |
Time-based | 3.34 (0.84) | 3.34 (0.79) | 3.53 (0.73) | 0.517 | 0.010 |
Subjective and Objective Cognitive Assessments | Pre-C/T Cancer Patients (N = 68) | Post-C/T Cancer Patients (N = 35) | Non-Cancer Controls (N =30) | ANCOVA † | ||
---|---|---|---|---|---|---|
Mean (SD) | Mean (SE) | Mean (SE) | p | η2 | Post Hoc Tests ‡ | |
Functional Assessment of Cancer Therapy Cognitive Scale (FACT-Cog) | 119.29 (10.67) | 119.26 (9.40) | 116.13 (16.25) | 0.006 | 0.077 | Pre-C/T > Control |
Perceived Cognitive Impairment | 66.00 (6.48) | 66.29 (5.71) | 64.50 (9.70) | 0.031 | 0.054 | Pre-C/T > Control |
Comments from Others | 15.71 (0.90) | 15.60 (0.78) | 15.27 (1.82) | 0.052 | 0.046 | |
Perceived Cognitive Abilities | 22.21 (3.74) | 21.94 (3.43) | 21.30 (4.79) | 0.019 | 0.061 | Pre-C/T > Control |
Impact of Perceived Cognitive Impairments on Quality of Life | 15.38 (1.99) | 15.43 (1.42) | 15.07 (2.16) | 0.058 | 0.044 | |
Attention function | ||||||
Digit Span | 11.31 (2.85) | 11.06 (3.42) | 12.01 (2.92) | 0.440 | 0.013 | |
Color Trails Test 1 | 51.36 (19.93) | 48.80 (23.06) | 47.27 (19.05) | 0.623 | 0.007 | |
Executive function | ||||||
Semantic Association of Verbal Fluency | 38.99 (8.29) | 37.43 (8.76) | 44.43 (8.22) | 0.011 * | 0.070 | Control > pre-C/T Control > post-C/T |
Orthographical Fluency Test | 17.79 (7.70) | 17.91 (7.72) | 20.44 (5.84) | 0.708 | 0.005 | |
Color Trails Test 2 | 97.16 (34.24) | 97.80 (35.02) | 88.67 (29.77) | 0.697 | 0.006 | |
Memory function | ||||||
Word List—Total immediate recall | 9.96 (2.52) | 9.69 (2.81) | 10.93 (2.94) | 0.693 | 0.006 | |
Word List—Long-delay recall | 10.57 (2.58) | 10.69 (2.53) | 10.97 (2.68) | 0.709 | 0.005 | |
Word List—Recognition | 11.09 (2.42) | 11.43 (2.31) | 11.23 (2.21) | 0.504 | 0.011 | |
Visuospatial construction | ||||||
Block Design | 9.43 (2.94) | 8.74 (3.43) | 9.67 (3.20) | 0.086 | 0.038 | |
Processing speed | ||||||
Digit Symbol Substitution | 10.26 (2.72) | 10.40 (2.69) | 11.13 (2.93) | 0.975 | 0.000 | |
Prospective memory | ||||||
Event-based | 4.13 (1.24) | 3.89 (0.33) | 3.87 (0.43) | 0.115 | 0.034 | |
Time-based | 3.34 (0.84) | 3.34 (0.80) | 3.53 (0.73) | 0.328 | 0.018 |
Predictors | Non cancer (n = 30) | Pre-C/T (n = 68) | Post-C/T (n = 35) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
β | R2 | ΔR2 | p-Value | Confidence Interval (CI) | β | R2 | ΔR2 | p-Value | CI | β | R2 | ΔR2 | p-Value | CI | ||
FACT-Cog | 0.599 | 0.099 | 0.012 | 0.155 | 0168 | 0.001 | 0.33~1.19 | 0.429 | 0.212 | 0.001 | ||||||
Age | −0.43 | 0.001 | −0.68~−0.18 | |||||||||||||
HADS | −2.08 | 0.012 | −3.68~ | −0.49 | ||||||||||||
PHQ-9 | −1.48 | 0.001 | −2.27~−0.68 | |||||||||||||
BFI_interference | −7.01 | <0.001 | −10.16~ | −3.85 | −0.73 | −1.13~−0.33 | ||||||||||
FACT-PCI | 0.569 | 0.084 | 0.025 | 0.334 | 0.058 | 0.019 | 0.397 | 0.078 | 0.044 | |||||||
Age | 0.16 | 0.011 | 0.04~0.27 | −0.22 | 0.007 | −0.37~−0.06 | ||||||||||
BMI | −0.40 | 0.044 | −0.78~−0.01 | |||||||||||||
PHQ-9 | −0.40 | 0.019 | −0.72~−0.07 | −0.71 | 0.008 | −1.23~−0.20 | ||||||||||
BFI_interference | −4.83 | <0.001 | −6.63~ | −3.03 | −0.36 | 0.005 | −0.61~−0.11 | |||||||||
Log IL-5 | −7.98 | 0.025 | −14.87~ | −1.08 | −0.73 | −1.13~−0.33 | ||||||||||
FACT-PCA | 0.443 | 0.115 | 0.021 | 0.227 | 0.069 | 0.017 | 0.340 | 0.144 | 0.010 | |||||||
Age | −0.17 | 0.001 | −0.27~−0.08 | |||||||||||||
IQ | 0.01 | 0.005 | 0.03~0.17 | |||||||||||||
PHQ | −0.23 | 0.017 | −0.41~−0.04 | |||||||||||||
HADS | −0.76 | 0.010 | −1.32~ | −0.02 | −0.51 | 0.010 | −0.89~−0.13 | |||||||||
BFI_interference | −1.32 | 0.021 | −2.43~ | −0.21 | ||||||||||||
Log IL-10 | 3.88 | 0.011 | 0.97~ | 6.79 | 3.66 | 0.002 | 1.43~5.89 | |||||||||
Log IL-13 | −2.28 | 0.008 | −3.95~−0.62 | |||||||||||||
SFT | 0.218 | 0.245 | 0.005 | 0.144 | 0157 | 0.001 | 0.458 | 0.077 | 0.036 | |||||||
Years of education | 1.02 | 0.32~ | 1.72 | 0.76 | 0.33~1.19 | |||||||||||
IQ | 0.27 | 0.002 | 0.11~0.44 | |||||||||||||
HADS-A | 1.87 | 0.001 | 0.86~2.87 | |||||||||||||
PHQ-9 | −0.90 | 0.036 | −1.73~−0.06 | |||||||||||||
Log IL-13 | −4.94 | 0.008 | −8.46~−1.42 |
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Chen, V.C.-H.; Lin, C.-K.; Hsiao, H.-P.; Tzang, B.-S.; Hsu, Y.-H.; Wu, S.-I.; Stewart, R. Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer. Cancers 2021, 13, 2576. https://doi.org/10.3390/cancers13112576
Chen VC-H, Lin C-K, Hsiao H-P, Tzang B-S, Hsu Y-H, Wu S-I, Stewart R. Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer. Cancers. 2021; 13(11):2576. https://doi.org/10.3390/cancers13112576
Chicago/Turabian StyleChen, Vincent Chin-Hung, Chin-Kuo Lin, Han-Pin Hsiao, Bor-Show Tzang, Yen-Hsuan Hsu, Shu-I Wu, and Robert Stewart. 2021. "Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer" Cancers 13, no. 11: 2576. https://doi.org/10.3390/cancers13112576