Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence

Theodore M. Brasky; Ashley S. Felix; David E. Cohn; D. Scott McMeekin; David G. Mutch; William T. Creasman; Premal H. Thaker; Joan L. Walker; Richard G. Moore; Shashikant B. Lele; Saketh R. Guntupalli; Levi S. Downs; Christa I. Nagel; John F. Boggess; Michael L. Pearl; Olga B. Ioffe; Kay J. Park; Shamshad Ali; Louise A. Brinton

doi:10.1093/jnci/djw251

Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence

Theodore M. Brasky, Ashley S. Felix, David E. Cohn, D. Scott McMeekin, David G. Mutch, William T. Creasman, Premal H. Thaker, Joan L. Walker, Richard G. Moore, Shashikant B. Lele, Saketh R. Guntupalli, Levi S. Downs, Christa I. Nagel, John F. Boggess, Michael L. Pearl, Olga B. Ioffe, Kay J. Park, Shamshad Ali, Louise A. Brinton

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Abstract

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained frommedical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR=1.66, 95% CI=1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR=2.23, 95% CI=1.19 to 4.18, two-sided Ptrend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.

Original language	English
Journal	Journal of the National Cancer Institute
Volume	109
Issue number	3
DOIs	https://doi.org/10.1093/jnci/djw251
State	Published - Mar 2017

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Brasky, T. M., Felix, A. S., Cohn, D. E., McMeekin, D. S., Mutch, D. G., Creasman, W. T., Thaker, P. H., Walker, J. L., Moore, R. G., Lele, S. B., Guntupalli, S. R., Downs, L. S., Nagel, C. I., Boggess, J. F., Pearl, M. L., Ioffe, O. B., Park, K. J., Ali, S., & Brinton, L. A. (2017). Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence. Journal of the National Cancer Institute, 109(3). https://doi.org/10.1093/jnci/djw251

@article{4bd6e7962e244de09989b4dcafbc903e,

title = "Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence",

abstract = "Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained frommedical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR=1.66, 95% CI=1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR=2.23, 95% CI=1.19 to 4.18, two-sided Ptrend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.",

author = "Brasky, {Theodore M.} and Felix, {Ashley S.} and Cohn, {David E.} and McMeekin, {D. Scott} and Mutch, {David G.} and Creasman, {William T.} and Thaker, {Premal H.} and Walker, {Joan L.} and Moore, {Richard G.} and Lele, {Shashikant B.} and Guntupalli, {Saketh R.} and Downs, {Levi S.} and Nagel, {Christa I.} and Boggess, {John F.} and Pearl, {Michael L.} and Ioffe, {Olga B.} and Park, {Kay J.} and Shamshad Ali and Brinton, {Louise A.}",

note = "Publisher Copyright: {\textcopyright} The Author 2017.",

year = "2017",

month = mar,

doi = "10.1093/jnci/djw251",

language = "English",

volume = "109",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

number = "3",

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Brasky, TM, Felix, AS, Cohn, DE, McMeekin, DS, Mutch, DG, Creasman, WT, Thaker, PH, Walker, JL, Moore, RG, Lele, SB, Guntupalli, SR, Downs, LS, Nagel, CI, Boggess, JF, Pearl, ML, Ioffe, OB, Park, KJ, Ali, S & Brinton, LA 2017, 'Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence', Journal of the National Cancer Institute, vol. 109, no. 3. https://doi.org/10.1093/jnci/djw251

TY - JOUR

T1 - Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence

AU - Brasky, Theodore M.

AU - Felix, Ashley S.

AU - Cohn, David E.

AU - McMeekin, D. Scott

AU - Mutch, David G.

AU - Creasman, William T.

AU - Thaker, Premal H.

AU - Walker, Joan L.

AU - Moore, Richard G.

AU - Lele, Shashikant B.

AU - Guntupalli, Saketh R.

AU - Downs, Levi S.

AU - Nagel, Christa I.

AU - Boggess, John F.

AU - Pearl, Michael L.

AU - Ioffe, Olga B.

AU - Park, Kay J.

AU - Ali, Shamshad

AU - Brinton, Louise A.

PY - 2017/3

Y1 - 2017/3

N2 - Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained frommedical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR=1.66, 95% CI=1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR=2.23, 95% CI=1.19 to 4.18, two-sided Ptrend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.

AB - Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained frommedical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR=1.66, 95% CI=1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR=2.23, 95% CI=1.19 to 4.18, two-sided Ptrend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.

UR - http://www.scopus.com/inward/record.url?scp=85017018339&partnerID=8YFLogxK

U2 - 10.1093/jnci/djw251

DO - 10.1093/jnci/djw251

M3 - Article

C2 - 28376204

AN - SCOPUS:85017018339

SN - 0027-8874

VL - 109

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 3

ER -

Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence

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