Survival Impact of Long-Term Tramadol Use on Breast Cancer for Patients with Chronic Pain: A Propensity Score-Matched Population-Based Cohort Study
Abstract
:1. Introduction
2. Patients and Methods
2.1. Data Sources and Study Cohort
2.2. Participant Selection
2.3. Propensity Scores Matching and Covariates
2.4. Statistical Analysis
3. Results
3.1. Study Cohort
3.2. All-Cause Death after Multivariate Cox Regression Analysis
3.3. Kaplan–Meier Survival Curve of Long-Term Tramadol Analgesic Users and Nonusers before Breast Cancer Diagnosis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
DDD | Defined Daily Dose |
HR | hazard ratio |
aHR | adjusted hazard ratio |
CI | confidence interval |
RCT | randomized controlled trial |
PSM | propensity score matching |
TCRD | Taiwan Cancer Registry database |
ICD-9-CM | International Classification of Diseases, Ninth Revision, Clinical Modification |
OS | overall survival |
CCI | Charlson comorbidity index |
NK | natural killer |
NSAID | nonsteroidal anti-inflammatory drugs |
AJCC | American Joint Committee on Cancer |
HER2 | Human Epidermal Growth factor Receptor-2 |
MCF-7 | Michigan Cancer Foundation-7 |
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Tramadol Analgesia | Non-Tramadol Analgesia | p-Value | |||
---|---|---|---|---|---|
N = 520 | N = 104 | ||||
N | % | N | % | ||
Sex | 0.8103 | ||||
Female | 492 | 94.62% | 99 | 95.19% | |
Male | 28 | 5.38% | 5 | 4.81% | |
Age (mean ± SD) | 59.36 ± 13.03 | 59.83 ± 13.68 | 0.7405 | ||
Age (years old) | 0.1211 | ||||
Age ≤ 65 | 351 | 67.50% | 67 | 64.42% | |
65y < Age ≤ 75 | 98 | 18.85% | 16 | 15.38% | |
75 < Age ≤ 85 | 54 | 10.38% | 19 | 18.27% | |
Age>85 | 17 | 3.27% | 2 | 1.92% | |
Comorbidities | |||||
CCI Score (mean ± SD) | 0.51 ± 0.95 | 0.52 ± 0.97 | 0.9403 | ||
CCI Score | 0.9681 | ||||
=0 | 376 | 72.31% | 75 | 72.12% | |
≥1 | 144 | 27.69% | 29 | 27.88% | |
Congestive Heart Failure | 21 | 4.04% | 7 | 6.73% | 0.2260 |
Dementia | 9 | 1.73% | 3 | 2.88% | 0.4341 |
Chronic Pulmonary Disease | 59 | 11.35% | 11 | 10.58% | 0.8205 |
Rheumatic Disease | 12 | 2.31% | 2 | 1.92% | 0.8090 |
Hepatitis B/C | 53 | 10.19% | 7 | 6.73% | 0.2743 |
Diabetes with complications | 17 | 3.27% | 2 | 1.92% | 0.4658 |
Hemiplegia and Paraplegia | 0 | 0.00% | 0 | 0.00% | - |
Renal Disease | 10 | 1.92% | 3 | 2.88% | 0.5308 |
AIDS | 0 | 0.00% | 0 | 0.00% | - |
Diabetes | 79 | 15.19% | 16 | 15.38% | 0.9603 |
Hyperlipidemia | 98 | 18.85% | 18 | 17.31% | 0.7128 |
ESRD | 0 | 0.00% | 0 | 0.00% | - |
Liver cirrhosis | 83 | 15.96% | 17 | 16.35% | 0.9222 |
AMI | 10 | 1.92% | 2 | 1.92% | 1.0000 |
Coronary Arterial Disease | 55 | 10.58% | 13 | 12.50% | 0.5656 |
Hemorrhage Stroke | 13 | 2.50% | 2 | 1.92% | 0.7259 |
Ischemia Stroke | 10 | 1.92% | 2 | 1.92% | 1.0000 |
Income levels (NTD/month) | 0.9765 | ||||
Low income | 10 | 1.92% | 2 | 1.92% | |
Income ≤ 20,000 | 258 | 49.62% | 54 | 51.92% | |
20,000 < Income ≤ 30,000 | 176 | 33.85% | 34 | 32.69% | |
Income > 30,000 | 76 | 14.62% | 14 | 13.46% | |
Urbanization | 0.6248 | ||||
Rural | 104 | 20.00% | 23 | 22.12% | |
Urban | 416 | 80.00% | 81 | 77.88% | |
Menopausal status | 0.914 | ||||
Postmenopausal | 338 | 65.00% | 67 | 64.42% | |
Premenopausal | 182 | 35.00% | 37 | 35.58% | |
HER2 status | 1.000 | ||||
Negative | 415 | 79.81% | 83 | 79.81% | |
Positive | 105 | 20.19% | 21 | 20.19% | |
Nodal surgery | 1.000 | ||||
SLNB | 360 | 69.23% | 72 | 69.23% | |
ALND | 160 | 30.77% | 32 | 30.77% | |
AJCC clinical stage | 1.000 | ||||
I | 270 | 51.92% | 54 | 51.92% | |
II | 130 | 25.00% | 26 | 25.00% | |
III | 120 | 23.08% | 24 | 23.08% | |
Hormone receptor | 1.000 | ||||
Negative | 120 | 23.08% | 24 | 23.08% | |
Positive | 400 | 76.92% | 80 | 76.92% | |
Breast surgery | 1.000 | ||||
Total mastectomy | 85 | 16.35% | 17 | 16.35% | |
Breast-conserving surgery | 435 | 83.65% | 87 | 83.65% | |
Differentiation | 1.000 | ||||
I | 80 | 15.38% | 16 | 15.38% | |
II | 230 | 44.23% | 46 | 44.23% | |
III | 210 | 40.38% | 42 | 40.38% | |
Chemotherapy | 0.898 | ||||
No | 273 | 52.50% | 54 | 51.92% | |
Yes | 247 | 47.50% | 50 | 48.08% | |
Adjuvant radiotherapy | 0.834 | ||||
No | 87 | 16.73% | 17 | 16.35% | |
Yes | 433 | 83.27% | 87 | 83.65% | |
Follow-up time, Years, (mean ± SD) | 5.78 ± 4.45 | 3.12 ± 3.20 | <0.0001 | ||
All-cause Death | <0.0001 | ||||
Not | 397 | 76.35% | 60 | 57.69% | |
Yes | 123 | 23.65% | 44 | 42.31% |
Crude HR (95% CI) | Adjusted HR * (95% CI) | p-Value | |||
---|---|---|---|---|---|
Tramadol Analgesia (ref. Non-Tramadol Analgesia) | |||||
Tramadol use | 3.33 | (2.34–4.75) | 3.45 | (2.36–5.04) | <0.001 |
Sex (ref. female) | |||||
male | 2.76 | (1.71–4.46) | 1.34 | (0.74–2.41) | 0.3310 |
Age (ref. Age ≤ 65 years old) | |||||
65 < Age ≤ 75 | 1.61 | (1.09–2.38) | 1.6 | (1.03–2.46) | 0.035 |
75 < Age ≤ 85 | 2.51 | (1.66–3.78) | 2.6 | (1.63–4.17) | <0.001 |
Age > 85 | 5.86 | (3.18–10.78) | 5.09 | (2.33–11.12) | <0.001 |
Comorbidities | |||||
Congestive Heart Failure (ref. no) | 1.44 | (0.90–2.30) | 1.07 | (0.94–1.77) | 0.913 |
Dementia (ref. no) | 2.01 | (0.86–4.11) | 1.26 | (0.49–2.83) | 0.657 |
Chronic Pulmonary Disease (ref. no) | 1.03 | (0.77–1.40) | 1.01 | (0.74,1.39) | 0.642 |
Rheumatic Disease (ref. no) | 1.08 | (0.81–2.17) | 1.05 | (0.90–2.05) | 0.341 |
Hepatitis B/C (ref. no) | 1.06 | (0.89–2.02) | 1.02 | (0.91–1.86) | 0.410 |
Diabetes with complications (Severe diabetes) (ref. no) | 1.05 | (0.59–3.21) | 1.03 | (0.69–2.77) | 0.538 |
Renal Disease (ref. no) | 1.14 | (0.91–2.00) | 1.08 | (0.81–1.81) | 0.308 |
Diabetes (ref. no) | 1.77 | (1.2–2.6) | 1.48 | (0.92–2.36) | 0.104 |
Hyperlipidemia (ref. no) | 1.05 | (0.7–1.59) | 1.09 | (0.54–1.49) | 0.683 |
Liver cirrhosis (ref. no) | 1.00 | (0.64–1.56) | 0.75 | (0.45–1.25) | 0.272 |
AMI (ref. no) | 2.15 | (0.88–5.25) | 1.38 | (0.48–3.92) | 0.551 |
Coronary Arterial Disease (ref. no) | 1.51 | (0.95–2.39) | 0.97 | (0.54–1.73) | 0.909 |
Hemorrhage Stroke (ref. no) | 2.08 | (0.92–4.7) | 2.05 | (0.82–5.15) | 0.126 |
Ischemia Stroke (ref. no) | 1.46 | (0.46–4.57) | 1.03 | (0.26–3.31) | 0.912 |
Urbanization (ref. Rural) | |||||
Urban | 0.74 | (0.52–1.05) | 0.76 | (0.52–1.12) | 0.161 |
Income levels (ref. low income, NTD/month) | |||||
Income ≤ 20,000 | 0.50 | (0.23–1.07) | 0.71 | (0.31–1.65) | 0.425 |
20,000 < Income ≤ 30,000 | 0.30 | (0.14–0.68) | 0.54 | (0.22–1.3) | 0.170 |
Income > 30,000 | 0.26 | (0.11–0.63) | 0.49 | (0.18–1.3) | 0.152 |
Menopausal status (ref: Postmenopausal) | |||||
Premenopausal | 1.11 | (0.98–1.71) | 1.10 | (0.90–1.21) | 0.317 |
HER2 (ref: Negative) | |||||
Positive | 1.49 | (1.01–1.70) | 1.19 | (0.84–1.10) | 0.488 |
Breast surgery (ref: Total mastectomy) | |||||
Breast-conserving surgery | 1.09 | (0.80–1.15) | 1.02 | (0.79–1.09) | 0.473 |
Nodal surgery (ref: SLND) | |||||
ALND | 1.11 | (0.66–1.33) | 1.06 | (0.68–1.27) | 0.501 |
AJCC clinical stage (ref. stage I) | |||||
Stage II | 1.21 | (0.93–2.16) | 1.20 | (0.96–1.90) | 0.081 |
Stage III | 1.91 | (0.69–2.01) | 1.59 | (0.83–1.81) | 0.094 |
Hormone receptor (ref. Negative) | |||||
Positive | 0.88 | (0.79–1.38) | 0.93 | (0.87–1.29) | 0.441 |
Differentiation (ref: Grade I) | |||||
Grade II | 1.06 | (0.92–1.16) | 1.03 | (0.91–1.17) | 0.061 |
Grade III | 1.09 | (0.94–1.18) | 1.08 | (0.97–1.15) | 0.073 |
Chemotherapy (ref: No) | |||||
Yes | 0.71 | (0.51–1.09) | 0.82 | (0.62–1.10) | 0.524 |
Adjuvant radiotherapy (ref: No) | |||||
Yes | 0.88 | (0.61–1.20) | 0.89 | (0.62–1.19) | 0.415 |
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Sun, M.; Chang, C.-L.; Lu, C.-Y.; Wu, S.-Y.; Zhang, J. Survival Impact of Long-Term Tramadol Use on Breast Cancer for Patients with Chronic Pain: A Propensity Score-Matched Population-Based Cohort Study. J. Pers. Med. 2022, 12, 384. https://doi.org/10.3390/jpm12030384
Sun M, Chang C-L, Lu C-Y, Wu S-Y, Zhang J. Survival Impact of Long-Term Tramadol Use on Breast Cancer for Patients with Chronic Pain: A Propensity Score-Matched Population-Based Cohort Study. Journal of Personalized Medicine. 2022; 12(3):384. https://doi.org/10.3390/jpm12030384
Chicago/Turabian StyleSun, Mingyang, Chia-Lun Chang, Chang-Yun Lu, Szu-Yuan Wu, and Jiaqiang Zhang. 2022. "Survival Impact of Long-Term Tramadol Use on Breast Cancer for Patients with Chronic Pain: A Propensity Score-Matched Population-Based Cohort Study" Journal of Personalized Medicine 12, no. 3: 384. https://doi.org/10.3390/jpm12030384