br Table br Study characteristics by
Study characteristics by Long-term NSAID Use.
Study characteristics No Long-term Long-term p-value
Median Household Income
Cancer Related Pain
Long-term Use of Steroids,
Past Surgical History
Non-Cancer Related Pain
Other Substance Abuse
Dependent Other substance 8.16 9.4
Mean (Standard Error of Mean in parenthesis) ¶ Categorical variables reported as percentage
Crude and Adjusted Odds Ratios for Opioid Abuse among hospitalized patients with Breast cancer.
Eﬀect cORa aORb (aOR 95% CI) aOR pvalue
a cOR Crude Odds Ratio
b aOR Adjusted Odds Ratio
compared to patients without dependent substance abuse. Similarly, odds of abuse were higher among subjects with non-dependent non-opioid substance abuse (aOR 2.33; 95% CI [1.9–2.87]) compared to subjects without a history of non-dependent non-opioid substance abuse. In addition, significantly higher odds were found among patients with depression, anxiety disorder, and psychosocial stress. The odds of opioid abuse were not statistically diﬀerent between the levels of past surgical history.
Association between long-term NSAID use and inpatient mortality
No significant association with inpatient mortality was found among patients with a diagnosis of opioid abuse, anxiety disorder, and psychosocial stress; however, the odds of mortality were increased for depression.
Crude and Adjusted Odds Ratios for Inpatient mortality among Hospitalized patients with Breast cancer.
Eﬀect cORa aORb (aOR
aOR p value
a cOR Crude Odds Ratio
b aOR Adjusted Odds Ratio
Association between long-term NSAID use and LOS
Our study highlights the benefits of long-term NSAID use with re-spect to opioid abuse and adds to the limited number of studies Cancer Treatment and Research Communications 21 (2019) 100156
Mean, crude and adjusted mean ratios for length of stay among hospitalized patients with breast cancer.
Eﬀect Mean cMR aMR (95% CI) P value
Long-term current NSAID use 7.12
cMR Crude Mean Ratio.
aMR Adjusted Mean Ratio.
exploring this EIPA relationship among hospitalized patients with breast cancer. Our findings suggest that long-term NSAID use is protective against opioid abuse. Even after adjusting for several covariates, this association remained significant. In addition, we found similar asso-ciations between long-term NSAID use and hospitalization outcomes such as inpatient mortality and LOS.
The anti-neoplastic  and neuroprotective eﬀects [31,32] of NSAIDs as described in previous studies, may provide a biologically plausible and mechanistic explanation of the observed protective eﬀect of NSAID use on opioid abuse risk. However, additional processes currently un-identified may be involved, warranting further studies to better understand this association as well as optimal dosing and dura-tion in this population.
Compared to patients who were not on long-term NSAID use, those with a history of long-term NSAID use had lower inpatient mortality. This is not surprising as studies have documented improved cardio-vascular risk factors among patients who were placed on long-term NSAIDs such as aspirin, and prognostic indices and survival in cancers including breast cancer, colorectal cancer and lung cancer [12,14,33,34]. A possible explanation could be linked to the fact that since pain suppresses immunity, and immunity is vital for protecting against cancer, pain relief would lead to improved survival [35,36]. Another possible explanation is that NSAIDs have antineoplastic prop-erties through their inhibition of cyclooxygenase-2 enzyme (COX-2); there is evidence of an inverse relationship between COX-2 expression and tumor metastases .
We found that long-term NSAID use was associated with a shorter LOS. Our findings are consistent with other studies, which suggest that cancer-related pain (usually associated with advanced metastatic dis-ease especially to the bone) increases the likelihood of patient referral for specialist treatments such as radiotherapy [35,38].
This study has several important limitations which directly relate to the data available in the NIS database. First, the NIS database employs ICD-9 codes, which makes it impossible to determine the source of the opioid abuse, in addition to the potential for misreporting of opioid use resulting from the variations in code accuracy across hospitals and state. Second, we cannot rule out residual confounding from un-measured covariates such as characteristics of the breast tumor, dura-tion of opioid use and type of opioid. However, we carried out a robust methodological analysis and adjusted for comorbidity indices, previous chemotherapy and radiotherapy, the presence of cancer and non-cancer related pain. In addition, using breast cancer-specific hospitalization, our findings may not be generalizable to patients with other forms of cancer pain. Despite these limitations, the strength of the study lies in the inclusion of a large number of hospitalizations from a large socio-demographic pool, addressing pertinent issues in pain management and