br Cancer related pain br Breast cancer br National
National inpatient sample
Background: Improving survival rates among patients with breast cancer has been associated with an increase in the prevalence of co-morbidities like cancer-related pain. Opioids are an important component in the man-agement of pain among these patients. However, the progression from judicious use to abuse defeats the aim of pain control. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the first step in cancer-related pain management. Due to their anti-inflammatory, anti-neoplastic and neuroprotective properties, NSAIDs have been shown to reduce the risk of progression of certain cancers including breast cancers. In this study, we assessed whether an association exists between long-term NSAID use and opioid abuse among breast cancer survivors. We also explored the relationship between long-term NSAID use and inpatient mortality and length of stay (LOS). r> Methods: Using ICD-9-CM codes, we identified and selected women aged 18 years and older with breast cancer from the National Inpatient Sample. Our primary predictor was a history of long-term NSAID use. Multivariable regression models were employed in assessing the association between long-term NSAID use and opioid abuse, inpatient mortality and LOS.
Discussion: Further studies are needed to understand the underlying mechanism of the association between long-term NSAID use and opioid abuse.
Although the incidence of breast cancer continues to increase, the mortality rate among patients with breast cancer has steadily declined over the past 30 years due to improved disease detection and treatment options . The 2018 estimate for new cases of breast cancer was
266,120 with an 89.7% overall five-year survival rate between 2008 and 2014 . Better survival indices increase the likelihood that sur-vivors will report cancer-related pain as a complication of surgical treatment [3,4], chemotherapy , radiotherapy  or advanced dis-ease, potentially leading to a growing Cycloheximide requiring pain man-agement .
Corresponding author at: Department of Anesthesiology, Case Western Reserve University/MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, OH 44109, United States. E-mail address: [email protected] (N.E. Onyeakusi).
About 54% of the estimated 3418,124 breast cancer patients in the United States experience cancer-related pain [2,7]. The widely adopted WHO 1996 guidelines for cancer pain management recommends a stepwise approach for analgesic pharmacotherapy  and is conifers reported to provide pain relief to 70–90% of patients . The guidelines re-commend as a first step, the use of non-opioids such as NSAIDs with or without an adjuvant (e.g. corticosteroids, psychotropics) for mild pain. Adjuvant drugs serve to enhance the analgesic eﬀect of standard treatment, treat medication side eﬀects or comorbid conditions. In the event of persistent pain or increased severity, the WHO recommends the addition of an opioid analgesic . Despite the potent pain-re-lieving eﬀect of opioids, the progression from appropriate use to de-pendence and abuse presents serious risks with overall poor outcomes. Opioid abuse is not a new occurrence but in the past decade, has be-come a worsening public health problem .
Current evidence regarding the long-term benefits of NSAIDs to treat pain in cancer patients, though limited, show benefits . Chronic use of NSAIDs has been shown to improve survival in cancer patients through its anti-inflammatory properties [12–14]. NSAIDs, in addition to their analgesic eﬀects, have been shown to have anti-neo-plastic properties by inhibiting tumor growth,  and reducing the risk of developing certain cancers  including breast cancer . They are frequently used in the management of various types of cancer pain, either alone or in combination with opioids . Additionally, NSAID use has been shown to reduce the requirements for opioids with up to 50% decrease in the need for morphine administration noted [19–21]. Given the multiple benefits of NSAIDs highlighted above, we sought to determine whether a relationship exists between long-term NSAID use and opioid abuse among women with breast cancer. Ad-ditionally, we evaluated the impact of long-term NSAID use on sec-ondary outcomes, specifically inpatient mortality and LOS.
Data source and study population
We conducted a retrospective study using secondary de-identified data from the 2007 to 2014 National Inpatient Sample (NIS). The NIS is a database component of the Healthcare Cost and Utilization Project (HCUP) administered by the Agency for Healthcare Research and Quality (AHRQ). The NIS database is the largest publicly available all-payer inpatient healthcare database in the US and consists of discharge records from NIS participating hospitals, representing over 7 million unweighted and 35 million weighted annual inpatient hospital stays [22,23]. As the NIS is a public use database, our study did not require an IRB approval.