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EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
EXPERT COMMENTARY
Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.1 Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.
Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.2-6
_
Details of the study
This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.
Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).
The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.
Study strengths and weaknesses
This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.
However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.
In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.
Based on these current data, there is insufficient evidence to suggest the use of low-dose aspirin for chemoprophylaxis of ovarian cancer. In order to suggest the use of a drug for prophylaxis the benefits must outweigh the risks, and in the case of NSAIDs, this has yet to be confirmed.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
- Poole EM, Lee IM, Ridker PM, et al. A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol. 2013;178:1256-1264.
- Trabert B, Ness RB, Lo-Ciganic WH, et al. Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014;106:djt431.
- Peres LC, Camacho F, Abbott SE, et al. Analgesic medication use and risk of epithelial ovarian cancer in African American women. Br J Cancer. 2016;114(7):819-825.
- Murphy MA, Trabert B, Yang HP, et al. Non-steroidal antiinflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer Causes Control. 2012;23:1839-1852.
- Brasky TM, Liu J, White E, et al. Non-steroidal antiinflammatory drugs and cancer risk in women: results from the Women’s Health Initiative. Int J Cancer. 2014;135:1869-1883.
- Lacey JV Jr, Sherman ME, Hartge P, et al. Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer. 2004;108:281-286.
