Melissa A Merritt1, Megan S Rice2, Mollie E Barnard3, Susan E Hankinson4, Ursula A Matulonis5, Elizabeth M Poole6, Shelley S Tworoger7. 1. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. Electronic address: melissa.merritt@hawaii.edu. 2. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 3. Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA. 4. Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA. 5. Gynecologic Oncology Program, Dana-Farber Cancer Institute, Boston, MA, USA. 6. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 7. Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
Abstract
BACKGROUND: Ovarian cancer is the fifth most common cause of cancer death among women in the USA. In this study, our objective was to determine whether modifiable exposures to common analgesics outside of standard treatment influence prognosis in patients with ovarian cancer. METHODS: The Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) are ongoing prospective studies of 121 700 and 116 429 US nurses who have completed biennial questionnaires since 1976 and 1989, respectively. We retrieved information from medical records, death certificates, or linkage to a state or Surveillance, Epidemiology, and End Results (SEER) cancer registry on ovarian cancer cases. Eligible participants had confirmed invasive, stage I-III epithelial ovarian cancer, and had data available on analgesic use. The primary objective was to determine whether self-reported regular use (≥2 days per week) of aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), or paracetamol before and after ovarian cancer diagnosis, was associated with ovarian cancer-specific survival. We used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for these associations, adjusting for age and year of diagnosis, disease stage, and histology. FINDINGS: Between June 1, 1976, and May 31, 2012, for the NHS and between June 1, 1989, and May 31, 2013, for NHSII, 1789 participants of the NHS and NHSII studies were diagnosed with epithelial ovarian cancer and 1143 (64%) were eligible to be included in this study; 1031 (90%) of 1143 cases were included in the pre-diagnosis exposure analysis and 964 cases (84%) in the post-diagnosis exposure analysis. Compared with never-users, participants who reported recent (current use in the past 2 years) post-diagnosis use of aspirin (HR 0·68 [95% CI 0·52-0·89]) and non-aspirin NSAIDs (HR 0·67 [95% CI 0·51-0·87]) had an improved ovarian cancer-specific survival. Any type of analgesic use pre-diagnosis, and post-diagnosis use of paracetamol, were not positively associated with ovarian cancer-specific survival. In analyses of change in analgesic use from pre-diagnosis to post-diagnosis, those participants who became recent users of aspirin (HR 0·44 [95% CI 0·26-0·74]) or became recent users of non-aspirin NSAIDs (HR 0·46 [95% CI 0·29-0·73]) post-diagnosis had a lower risk of ovarian cancer-specific death than never-users. INTERPRETATION: Recent use of aspirin or non-aspirin NSAIDs, defined as current use in the past 2 years, after diagnosis appears to improve ovarian cancer-specific survival. If these results are confirmed in further studies, further research should explore potential synergistic effects of anti-inflammatory medications used in combination with standard ovarian cancer therapies to improve the prognosis for patients diagnosed with ovarian cancer. FUNDING: National Institutes of Health, National Cancer Institute, The Marsha Rivkin Center for Ovarian Cancer Research.
BACKGROUND:Ovarian cancer is the fifth most common cause of cancer death among women in the USA. In this study, our objective was to determine whether modifiable exposures to common analgesics outside of standard treatment influence prognosis in patients with ovarian cancer. METHODS: The Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) are ongoing prospective studies of 121 700 and 116 429 US nurses who have completed biennial questionnaires since 1976 and 1989, respectively. We retrieved information from medical records, death certificates, or linkage to a state or Surveillance, Epidemiology, and End Results (SEER) cancer registry on ovarian cancer cases. Eligible participants had confirmed invasive, stage I-III epithelial ovarian cancer, and had data available on analgesic use. The primary objective was to determine whether self-reported regular use (≥2 days per week) of aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), or paracetamol before and after ovarian cancer diagnosis, was associated with ovarian cancer-specific survival. We used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for these associations, adjusting for age and year of diagnosis, disease stage, and histology. FINDINGS: Between June 1, 1976, and May 31, 2012, for the NHS and between June 1, 1989, and May 31, 2013, for NHSII, 1789 participants of the NHS and NHSII studies were diagnosed with epithelial ovarian cancer and 1143 (64%) were eligible to be included in this study; 1031 (90%) of 1143 cases were included in the pre-diagnosis exposure analysis and 964 cases (84%) in the post-diagnosis exposure analysis. Compared with never-users, participants who reported recent (current use in the past 2 years) post-diagnosis use of aspirin (HR 0·68 [95% CI 0·52-0·89]) and non-aspirin NSAIDs (HR 0·67 [95% CI 0·51-0·87]) had an improved ovarian cancer-specific survival. Any type of analgesic use pre-diagnosis, and post-diagnosis use of paracetamol, were not positively associated with ovarian cancer-specific survival. In analyses of change in analgesic use from pre-diagnosis to post-diagnosis, those participants who became recent users of aspirin (HR 0·44 [95% CI 0·26-0·74]) or became recent users of non-aspirin NSAIDs (HR 0·46 [95% CI 0·29-0·73]) post-diagnosis had a lower risk of ovarian cancer-specific death than never-users. INTERPRETATION: Recent use of aspirin or non-aspirin NSAIDs, defined as current use in the past 2 years, after diagnosis appears to improve ovarian cancer-specific survival. If these results are confirmed in further studies, further research should explore potential synergistic effects of anti-inflammatory medications used in combination with standard ovarian cancer therapies to improve the prognosis for patients diagnosed with ovarian cancer. FUNDING: National Institutes of Health, National Cancer Institute, The Marsha Rivkin Center for Ovarian Cancer Research.
Authors: Nonna Kolomeyevskaya; Kevin H Eng; Anm Nazmul H Khan; Kassondra S Grzankowski; Kelly L Singel; Kirsten Moysich; Brahm H Segal Journal: Gynecol Oncol Date: 2015-05-20 Impact factor: 5.482
Authors: Ying Bao; Monica L Bertoia; Elizabeth B Lenart; Meir J Stampfer; Walter C Willett; Frank E Speizer; Jorge E Chavarro Journal: Am J Public Health Date: 2016-07-26 Impact factor: 9.308
Authors: Claudia Allemani; Hannah K Weir; Helena Carreira; Rhea Harewood; Devon Spika; Xiao-Si Wang; Finian Bannon; Jane V Ahn; Christopher J Johnson; Audrey Bonaventure; Rafael Marcos-Gragera; Charles Stiller; Gulnar Azevedo e Silva; Wan-Qing Chen; Olufemi J Ogunbiyi; Bernard Rachet; Matthew J Soeberg; Hui You; Tomohiro Matsuda; Magdalena Bielska-Lasota; Hans Storm; Thomas C Tucker; Michel P Coleman Journal: Lancet Date: 2014-11-26 Impact factor: 79.321
Authors: Britton Trabert; Roberta B Ness; Wei-Hsuan Lo-Ciganic; Megan A Murphy; Ellen L Goode; Elizabeth M Poole; Louise A Brinton; Penelope M Webb; Christina M Nagle; Susan J Jordan; Harvey A Risch; Mary Anne Rossing; Jennifer A Doherty; Marc T Goodman; Galina Lurie; Susanne K Kjær; Estrid Hogdall; Allan Jensen; Daniel W Cramer; Kathryn L Terry; Allison Vitonis; Elisa V Bandera; Sara Olson; Melony G King; Urmila Chandran; Hoda Anton-Culver; Argyrios Ziogas; Usha Menon; Simon A Gayther; Susan J Ramus; Aleksandra Gentry-Maharaj; Anna H Wu; Celeste Leigh Pearce; Malcolm C Pike; Andrew Berchuck; Joellen M Schildkraut; Nicolas Wentzensen Journal: J Natl Cancer Inst Date: 2014-02 Impact factor: 11.816
Authors: Suzanne C Dixon; Christina M Nagle; Nicolas Wentzensen; Britton Trabert; Alicia Beeghly-Fadiel; Joellen M Schildkraut; Kirsten B Moysich; Anna deFazio; Harvey A Risch; Mary Anne Rossing; Jennifer A Doherty; Kristine G Wicklund; Marc T Goodman; Francesmary Modugno; Roberta B Ness; Robert P Edwards; Allan Jensen; Susanne K Kjær; Estrid Høgdall; Andrew Berchuck; Daniel W Cramer; Kathryn L Terry; Elizabeth M Poole; Elisa V Bandera; Lisa E Paddock; Hoda Anton-Culver; Argyrios Ziogas; Usha Menon; Simon A Gayther; Susan J Ramus; Aleksandra Gentry-Maharaj; Celeste Leigh Pearce; Anna H Wu; Malcolm C Pike; Penelope M Webb Journal: Br J Cancer Date: 2017-03-28 Impact factor: 7.640
Authors: Naoko Sasamoto; Tianyi Wang; Mary K Townsend; A Heather Eliassen; Fred K Tabung; Edward L Giovannucci; Ursula A Matulonis; Kathryn L Terry; Shelley S Tworoger; Holly R Harris Journal: Br J Cancer Date: 2022-06-27 Impact factor: 9.075
Authors: Katharine K Brieger; Minh Tung Phung; Bhramar Mukherjee; Kelly M Bakulski; Hoda Anton-Culver; Elisa V Bandera; David D L Bowtell; Daniel W Cramer; Anna DeFazio; Jennifer A Doherty; Sian Fereday; Renée Turzanski Fortner; Aleksandra Gentry-Maharaj; Ellen L Goode; Marc T Goodman; Holly R Harris; Keitaro Matsuo; Usha Menon; Francesmary Modugno; Kirsten B Moysich; Bo Qin; Susan J Ramus; Harvey A Risch; Mary Anne Rossing; Joellen M Schildkraut; Britton Trabert; Robert A Vierkant; Stacey J Winham; Nicolas Wentzensen; Anna H Wu; Argyrios Ziogas; Lilah Khoja; Kathleen R Cho; Karen McLean; Jean Richardson; Bronwyn Grout; Anne Chase; Cindy McKinnon Deurloo; Kunle Odunsi; Brad H Nelson; James D Brenton; Kathryn L Terry; Paul D P Pharoah; Andrew Berchuck; Gillian E Hanley; Penelope M Webb; Malcolm C Pike; Celeste Leigh Pearce Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-11-17 Impact factor: 4.090
Authors: Tianyi Wang; Mary K Townsend; A Heather Eliassen; Kathryn L Terry; Mingyang Song; Melinda L Irwin; Shelley S Tworoger Journal: Int J Cancer Date: 2021-05-21 Impact factor: 7.316
Authors: Naoko Sasamoto; Tianyi Wang; Mary K Townsend; Jonathan L Hecht; A Heather Eliassen; Mingyang Song; Kathryn L Terry; Shelley S Tworoger; Holly R Harris Journal: Cancer Epidemiol Biomarkers Prev Date: 2021-03-02 Impact factor: 4.090