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Preventive medicines
Evidence review M
NICE Guideline, No. 241
Preventive medicines
Review question
How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
Introduction
Women with a familial ovarian cancer risk are motivated to take steps to reduce their risk of developing ovarian cancer. These women are offered surgery to remove their tubes and ovaries to mitigate this risk; however, surgery comes with its own inherent risk which may be unacceptable to some. Other women with familial ovarian cancer do not wish to have surgery due to its impact on fertility. Finally, others are not well enough to have the risk reducing surgery. In addition, surgery cannot reduce the risk of developing ovarian cancer completely. Therefore, other ways to reduce an individual’s risk of familial ovarian cancer are a priority to those with an inherited risk and their clinicians. It is known that certain medications can reduce the risk of ovarian cancer in all or specific inherited ovarian cancer syndromes. The evidence review will consider those medications, the evidence that supports them, their side effects and the effective doses needed to reduce ovarian cancer in those with a familial ovarian cancer risk.
Summary of the protocol
See Table 1 for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.
For further details see the review protocol in appendix A.
Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document (supplementary document 1).
Declarations of interest were recorded according to NICE’s conflicts of interest policy.
Effectiveness evidence
Included studies
Eight studies were included for this review, 1 systematic review of case-control and cohort studies (van Bommel 2023), 3 individual patient data meta-analyses (Hurwitz 2021, Hurwitz 2022, Hurwitz 2023), 1 cohort study (Michels 2018) and 3 case-control studies (Gross 1992, McLaughlin 2007, Vicus 2009).
Three individual patient data meta-analyses (Hurwitz 2021, Hurwitz 2022, Hurwitz 2023) compared frequent/daily aspirin use to infrequent/no aspirin use. Although there was some overlap in the study participants included in these studies, the studies focused on, and analysed different populations, namely women with a history of ovarian cancer only (Hurwitz 2021), women with a history of both ovarian cancer or breast cancer (Hurwitz 2022) and women with genetic data available (Hurwitz 2023). One systematic review compared oral contraceptive use to no oral contraceptive use among BRCA1/2 carriers (van Bommel 2023). One cohort study (Michels 2018) compared oral contraceptive use to no oral contraceptive use. Three case-controls studies compared oral contraceptive use to no oral contraceptive use (Gross 1992, McLaughlin 2007, Vicus 2009).
The included studies are summarised in Table 2.
See the literature search strategy in appendix B and study selection flow chart in appendix C.
Excluded studies
The landmark CAPP2 trial (Burn 2020) comparing aspirin to placebo for cancer prevention in people with Lynch syndrome could not be included as results were not reported separately for women.
Studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.
Summary of included studies
Summaries of the studies that were included in this review are presented in Table 2.
See the full evidence tables in appendix D and the forest plots in appendix E.
Summary of the evidence
Frequent aspirin use versus infrequent or no aspirin use
The evidence showed no important differences from frequent aspirin use in terms of ovarian cancer incidence relative to no or non-frequent use in women at all levels of risk, and the evidence also showed no evidence of an important difference in women with a family history of ovarian or breast cancer or in women with a family history of ovarian cancer only. This was also the case for different histological types of ovarian cancer in women with a family history of ovarian or breast cancer. This evidence was of low to moderate quality. Very low quality evidence showed no important difference in non-mucinous epithelial ovarian cancer incidence between frequent and infrequent/no aspirin use in women at all levels of risk.
The evidence also showed no evidence of important differences from frequent aspirin use on ovarian cancer risk relative to no or non-frequent use in women with a polygenic risk score for ovarian cancer at or above the median value, below the median value, or in any of the quintiles of polygenic risk score, with the exception of women with a polygenic risk score in the 60 – 80 percentile where an important benefit of frequent aspirin use was observed. However, this is likely to be a spurious finding since the interaction between polygenic score quintile and frequency of aspirin use was not statistically significant. There was also no evidence of important differences for the different histological types of ovarian cancer in women with a polygenic risk score for ovarian cancer at or above the median value. This evidence was of very low to low quality.
Oral contraceptive use versus no oral contraceptive use
When comparing oral contraceptive with no oral contraceptive use in women with BRCA1 or BRCA2 mutations there was an important benefit of oral contraceptive use in terms of reduced ovarian cancer incidence. This evidence was rated as moderate to high quality. However, there was some very low quality evidence that showed no evidence of important difference between oral contraceptive use and no use in terms of ovarian cancer incidence in women with BRCA1 mutation only. However, in this study the population was mixed, that is women with ovarian cancer and a history of breast cancer.
Different duration of oral contraceptive use versus no oral contraceptive use
When comparing different durations (0 to 1 year, 1.1 to 3 years, 3.1 to 5 years and more than 5 years) of oral contraceptive with no oral contraceptive use in women with BRCA1 or BRCA2 mutations there was an important benefit of oral contraceptive use in terms of reduced ovarian cancer incidence. This evidence was rated as moderate to high quality. However, other very low to low quality evidence showed no evidence of important differences between short-term (3 to 11 months) or longer term (1 to 4 years, 5 to 9 years, more than 10 years) use and no oral contraceptive use in terms of ovarian cancer incidence in women with a family history of ovarian cancer.
No evidence was identified for health related quality of life, treatment related adverse effects or overall survival.
See appendix F for full GRADE tables.
Economic evidence
Included studies
A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.
A single economic search was undertaken for all topics included in the scope of this guideline. See supplementary material 2 for details.
Excluded studies
Economic studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.
Summary of included economic evidence
No economic studies were identified which were applicable to this review question.
Economic model
No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.
The committee’s discussion and interpretation of the evidence
The outcomes that matter most
Ovarian cancer incidence was prioritised as a critical outcome by the committee. This is because the aim of the question was to determine whether medicines could prevent ovarian cancer in women at increased risk. Additionally, health related quality of life was also chosen as a critical outcome to capture the impact of medicines on the day-to-day lives of these women, including psychological and emotional factors.
Treatment related adverse effects was selected as an important outcome because any benefits in terms of incidence of ovarian cancer must be balanced against side effects caused by the medicines themselves. Finally overall survival was an important outcome because both prevention of ovarian cancer and serious adverse effects of treatment could impact overall survival and the balance of these is an important consideration when making treatment decisions.
The quality of the evidence
The quality of the evidence was assessed using GRADE and ranged from very low to high quality. Evidence was downgraded mainly due to imprecision in the effect estimates, as well as risk of bias: in some studies aspirin use was determined retrospectively by asking women to recall their usage. The evidence was also downgraded for indirectness in some cases due to the inclusion of women at all risk levels or for unexplained heterogeneity or because of the indirect study population (women with ovarian and breast cancer). Moreover, in 1 case-control study cases and controls were not matched.
No evidence was identified for health-related quality of life, treatment related adverse effects or overall survival. Due to the lack of evidence on some outcomes the committee also relied on their experience when making recommendations.
Benefits and harms
Aspirin
The committee noted that there was some overlap in the study participants included in the studies comprising this evidence but also that the studies focused on and analysed different populations. They discussed the evidence that showed no important difference in terms of ovarian cancer incidence when comparing frequent aspirin use to no or non-frequent use in women at all levels of risk and the evidence that showed no evidence of an important difference either in women with a family history of ovarian or breast cancer, in women with a family history of ovarian cancer only and in women with all levels of polygenic risk score values. They noted that this was also the case for different histological types of ovarian cancer. They therefore concluded that aspirin did not show a protective effect in terms of ovarian cancer and agreed that there was insufficient evidence to recommend the general use of aspirin for women with high risk of familial ovarian cancer. So, the committee did not recommend it for the sole purpose of reducing ovarian cancer risk. They discussed the quality of the evidence and noted that it was very low to moderate, despite the evidence not being of the highest quality rating it was consistent with their experience in expertise and so they did not recommend it for general protective use for ovarian cancer. The committee noted that there was existing NICE guidance on the use of aspirin to reduce the risk of colorectal cancer in people with Lynch syndrome. As people with Lynch syndrome were included in the scope of this guideline, the committee felt it was important to make cross reference to the NICE colorectal cancer guideline to ensure they were aware of this recommendation.
Combined oral contraceptives
The committee discussed the evidence for both comparisons (oral contraceptive use versus no use and different durations of use versus no use) that showed that there was an important benefit in reducing the risk of ovarian cancer associated with oral contraceptive. Whilst this was moderate to high quality evidence the committee drew on their knowledge that long-term use of oral contraceptives increased risk of breast cancer. They noted that this rather than the evidence quality was the important factor in clinical decision making and the strength of the recommendation that can be made because it is the balance between the protective benefit in relation to ovarian cancer and the risk of breast cancer that needs to be weight up. Although breast cancer was not an outcome in this evidence review, the committee agreed that this increased risk of breast cancer needs to be taken into account when thinking about oral contraceptives to prevent ovarian cancer. They agreed that the balance of risks and benefits will depend on the individual (for example how strong the family history is, which pathogenic variant the person may have and other potential risk factors). They therefore decided to only recommend oral contraceptives as a preventive medicine in particular circumstances: when the reduction in ovarian cancer risk (based on for example age, family history) may outweigh an increased breast cancer risk, and after taking into account whether the timing of risk-reducing surgery is appropriate or not (for example, it may not be appropriate because of age and planned pregnancy).
In the committee’s experience people are not always fully informed about the potential risks (increased risk of developing breast cancer) and benefits (reduced risk of developing ovarian cancer) of combined oral contraceptives which is necessary for informed decision making.
Research recommendation
The committee noted a lack of relevant evidence on preventive medicines and its inconsistency in women at increased risk of ovarian cancer to support decision making. They thought that some women may not want to undergo risk-reducing surgery and preventative medicine would then be a good option. Therefore they agreed to make a research recommendation on the effectiveness on preventive medicines.
Cost effectiveness and resource use
No existing economic evidence was identified for this review. The recommendations in this area reinforce current practice and implementing them will not require additional resources. Furthermore, the recommendations regarding oral contraceptives to prevent ovarian cancer will only apply to a small number of people since risk-reducing surgery is the preferred first-line treatment option for the majority of people.
Recommendations supported by this evidence review
This evidence review supports one cross reference and recommendations 1.7.1 to 1.7.43 and research recommendation 6 (on primary preventive medicines) in the NICE guideline.
References – included studies
Gross 1992
Gross, T P, Schlesselman, J J, Stadel, B V et al. The risk of epithelial ovarian cancer in short-term users of oral contraceptives. American journal of epidemiology 136(1): 46–53, 1992 [PubMed: 1415131]Hurwitz 2021
Hurwitz, Lauren M; Michels, Kara A; Cook, Michael B et al. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts. Cancer causes & control: CCC; vol. 32 (no. 1); 57–65, 2021 [PMC free article: PMC7855934] [PubMed: 33104910]Hurwitz 2022
Hurwitz, Lauren M, Townsend, Mary K, Jordan, Susan J et al. Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 40(36): 4207–4217, 2022 [PMC free article: PMC9916035] [PubMed: 35867953]Hurwitz 2023
Hurwitz, Lauren M, Webb, Penelope M, Jordan, Susan J et al. Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility. JAMA network open 6(2): e230666, 2023 [PMC free article: PMC9958519] [PubMed: 36826816]McLaughlin 2007
McLaughlin John R, Risch, Harwey A, Lubinski, Jan et al. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. The Lancet. Oncology; 2007; vol. 8 (no. 1); 26–34, 2007 [PubMed: 17196508]Michels 2018
Michels, Kara A, Pfeiffer, Ruth M, Brinton, Louise A et al. Modification of the Associations Between Duration of Oral Contraceptive Use and Ovarian, Endometrial, Breast, and Colorectal Cancers. JAMA oncology 4(4): 516–521, 2018 [PMC free article: PMC5885214] [PubMed: 29346467]Van Bommel 2023
van Bommel, Majke H D, IntHout, Joanna, Veldmate, Guus et al. Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis. Human reproduction update 29(2): 197–217, 2023 [PMC free article: PMC9976973] [PubMed: 36383189]Vicus 2009
Vicus D, Rosen B, Lubinski J, et al. Tamoxifen and the risk of ovarian cancer in BRCA1 mutation carriers. Gynecol Oncol.115(1):135–137, 2009 [PMC free article: PMC3756313] [PubMed: 19577280]Burn 2020
Burn J, Sheth H, Elliott F et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet (London, England) 395(10240): 1855–1863, 2020 [PMC free article: PMC7294238] [PubMed: 32534647]
Effectiveness
Economic
No economic studies were identified which were applicable to this review question.
Other
Appendices
Appendix A. Review protocols
Appendix B. Literature search strategies
Appendix C. Effectiveness evidence study selection
Appendix D. Evidence tables
Appendix E. Forest plots
Forest plots for review question: How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
No meta-analysis was conducted for this review question and so there are no forest plots.
Appendix F. GRADE tables
Appendix G. Economic evidence study selection
Study selection for: How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
No economic evidence was identified which was applicable to this review question.
Appendix H. Economic evidence tables
Economic evidence tables for review question: How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
No economic evidence was identified which was applicable to this review question.
Appendix I. Economic model
Economic model for review question: How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
No economic analysis was conducted for this review question.
Appendix J. Excluded studies
Excluded studies for review question: How effective are preventive medicines for reducing the incidence of ovarian cancer for women at increased risk of familial ovarian cancer?
Excluded effectiveness studies
Table 9Excluded studies and reasons for their exclusion
| Study | Code [Reason] |
|---|---|
| Baandrup, Louise, Faber, Mette T, Christensen, Jane et al. (2013) Nonsteroidal anti-inflammatory drugs and risk of ovarian cancer: systematic review and meta-analysis of observational studies. Acta obstetricia et gynecologica Scandinavica 92(3): 245–55 [PubMed: 23240575] | - Population not relevant to this review protocol |
| Beral, Valerie, Bull, Diana, Green, Jane et al. (2007) Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet (London, England) 369(9574): 1703–10 [PubMed: 17512855] | - Intervention in study does not match that specified in this review protocol |
| Burn J, Gerdes AM, Macrae F et al. (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet (London, England) 378(9809): 2081–2087 [PMC free article: PMC3243929] [PubMed: 22036019] |
- Population not relevant to this review protocol Results not reported separately for women (% of women not reported) |
| Burn J, Sheth H, Elliott F et al. (2020) Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. Lancet (London, England) 395(10240): 1855–1863 [PMC free article: PMC7294238] [PubMed: 32534647] |
- Population not relevant to this review protocol Results not reported separately for women (55.3% women) |
| Cook, Nancy R, Lee, I-Min, Gaziano, J Michael et al. (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294(1): 47–55 [PubMed: 15998890] | - Population not relevant to this review protocol |
| D’Alessandro, G., Frigerio, M., Barra, F. et al. (2021) Systematic review and meta-analysis on the impact of the levonorgestrel-releasing intrauterine system in reducing risk of ovarian cancer. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics [PMC free article: PMC9290617] [PubMed: 33969485] | - Intervention in study does not match that specified in this review protocol |
| Dixon, Suzanne C, Nagle, Christina M, Wentzensen, Nicolas et al. (2017) Use of common analgesic medications and ovarian cancer survival: results from a pooled analysis in the Ovarian Cancer Association Consortium. British journal of cancer 116(9): 1223–1228 [PMC free article: PMC5418444] [PubMed: 28350790] | - Population not relevant to this review protocol |
| Dorjgochoo, Tsogzolmaa, Shu, Xiao-Ou, Li, Hong-Lan et al. (2009) Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a large prospective study, from 1996 to 2006. International journal of cancer 124(10): 2442–9 [PMC free article: PMC2666967] [PubMed: 19170208] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Fairfield, Kathleen M, Hunter, David J, Fuchs, Charles S et al. (2002) Aspirin, other NSAIDs, and ovarian cancer risk (United States). Cancer causes & control : CCC 13(6): 535–42 [PubMed: 12195643] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Ferris, J.S., Daly, M.B., Buys, S.S. et al. (2014) Oral contraceptive and reproductive risk factors for ovarian cancer within sisters in the breast cancer family registry. British Journal of Cancer 110(4): 1074–1080 [PMC free article: PMC3929882] [PubMed: 24398512] | - Included in van Bommel 2023 |
| Friebel, Tara M; Domchek, Susan M; Rebbeck, Timothy R (2014) Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. Journal of the National Cancer Institute 106(6): dju091 [PMC free article: PMC4081625] [PubMed: 24824314] | - Systematic review, included studies checked for relevance |
| Gross, T P and Schlesselman, J J (1994) The estimated effect of oral contraceptive use on the cumulative risk of epithelial ovarian cancer. Obstetrics and gynecology 83(3): 419–24 [PubMed: 8127536] |
- Analyses not relevant to this review protocol All estimates appear to be unadjusted |
| Huang, Wen-Yi, Daugherty, Sarah E, Shiels, Meredith S et al. (2018) Aspirin Use and Mortality in Two Contemporary US Cohorts. Epidemiology (Cambridge, Mass.) 29(1): 126–133 [PMC free article: PMC5718934] [PubMed: 28863047] |
- Analyses not relevant to this review protocol No ovarian cancer-specific analyses in high-risk women |
| Huang, Zhezhou, Gao, Yutang, Wen, Wanqing et al. (2015) Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women’s Health Study. International journal of cancer 137(3): 607–14 [PMC free article: PMC4437849] [PubMed: 25556333] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Huber, D, Seitz, S, Kast, K et al. (2020) Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. Archives of gynecology and obstetrics 301(4): 875–884 [PMC free article: PMC8494665] [PubMed: 32140806] | - Systematic review, included studies checked for relevance |
| Iodice, S, Barile, M, Rotmensz, N et al. (2010) Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. European journal of cancer (Oxford, England : 1990) 46(12): 2275–84 [PubMed: 20537530] | - Systematic review, included studies checked for relevance |
| Iversen, Lisa, Sivasubramaniam, Selvaraj, Lee, Amanda J et al. (2017) Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners’ Oral Contraception Study. American journal of obstetrics and gynecology 216(6): 580e1–580e9 [PubMed: 28188769] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Moorman, Patricia G, Havrilesky, Laura J, Gierisch, Jennifer M et al. (2013) Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 31(33): 4188–98 [PubMed: 24145348] | - Systematic review, included studies checked for relevance |
| Movahedi, Mohammad, Bishop, D Timothy, Macrae, Finlay et al. (2015) Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33(31): 3591–7 [PubMed: 26282643] | - Outcomes in study do not match those specified in this review protocol |
| Murphy, Megan A, Trabert, Britton, Yang, Hannah P et al. (2012) Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review. Cancer causes & control : CCC 23(11): 1839–52 [PMC free article: PMC3469773] [PubMed: 22972000] | - Population not relevant to this review protocol |
| Ness, Roberta B, Dodge, Rhiannon C, Edwards, Robert P et al. (2011) Contraception methods, beyond oral contraceptives and tubal ligation, and risk of ovarian cancer. Annals of epidemiology 21(3): 188–96 [PMC free article: PMC3052991] [PubMed: 21109450] | - Included in Hurwitz 2022 |
| Park, Boyoung, Park, Sohee, Shin, Hai-Rim et al. (2016) Population attributable risks of modifiable reproductive factors for breast and ovarian cancers in Korea. BMC cancer 16: 5 [PMC free article: PMC4702325] [PubMed: 26732868] |
- Analyses not relevant to this review protocol No analyses of in high-risk women, instead family history was one of the factors adjusted for in the analyses, but with no results reported for that |
| Pinheiro, Simone P, Tworoger, Shelley S, Cramer, Daniel W et al. (2009) Use of nonsteroidal antiinflammatory agents and incidence of ovarian cancer in 2 large prospective cohorts. American journal of epidemiology 169(11): 1378–87 [PMC free article: PMC2727251] [PubMed: 19342401] | - Included in Hurwitz 2022 |
| Piver, M S, Baker, T R, Jishi, M F et al. (1993) Familial ovarian cancer. A report of 658 families from the Gilda Radner Familial Ovarian Cancer Registry 1981-1991. Cancer 71(2suppl): 582–8 [PubMed: 8420680] | - Information on intervention (birth control pills) not reported in sufficient detail to analyse (e.g., extent/definition of use unclear) |
| Pragout, D., Laurence, V., Baffet, H. et al. (2018) Contraception and cancer: CNGOF Contraception Guidelines. Gynecologie Obstetrique Fertilite et Senologie 46(12): 834–844 [PubMed: 30385358] | - Study not reported in English |
| Santucci, C., Gallus, S., Martinetti, M. et al. (2021) Aspirin and the risk of nondigestive tract cancers: An updated meta-analysis to 2019. International Journal of Cancer 148(6): 1372–1382 [PubMed: 32984948] | - Population not relevant to this review protocol |
| Schlesselman, J J (1995) Net effect of oral contraceptive use on the risk of cancer in women in the United States. Obstetrics and gynecology 85(5pt1): 793–801 [PubMed: 7724116] | - Population not relevant to this review protocol |
| Schuler, Susanne, Ponnath, Marvin, Engel, Jorg et al. (2013) Ovarian epithelial tumors and reproductive factors: a systematic review. Archives of gynecology and obstetrics 287(6): 1187–204 [PubMed: 23503972] |
- Study design not relevant to this review protocol Even though the study calls itself a systematic review, it is not reported accordingly, e.g., no inclusion/exclusion criteria reported, no analysis method reported |
| Soegaard, Marie, Jensen, Allan, Hogdall, Estrid et al. (2007) Different risk factor profiles for mucinous and nonmucinous ovarian cancer: results from the Danish MALOVA study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 16(6): 1160–6 [PubMed: 17548679] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Sorensen, H T, Friis, S, Norgard, B et al. (2003) Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study. British journal of cancer 88(11): 1687–92 [PMC free article: PMC2377131] [PubMed: 12771981] |
- Analyses not relevant to this review protocol No ovarian cancer-specific analyses in high-risk women |
| Tworoger, Shelley S, Fairfield, Kathleen M, Colditz, Graham A et al. (2007) Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. American journal of epidemiology 166(8): 894–901 [PubMed: 17656616] |
- Analyses not relevant to this review protocol No analyses in high-risk women |
| Whelan, Eilbhe, Kalliala, Ilkka, Semertzidou, Anysia et al. (2022) Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature. Cancers 14(11) [PMC free article: PMC9179274] [PubMed: 35681688] | - Population not relevant to this review protocol |
| Whittemore, A S, Balise, R R, Pharoah, P D P et al. (2004) Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. British journal of cancer 91(11): 1911–5 [PMC free article: PMC2410144] [PubMed: 15545966] | - Included in van Bommel 2023 |
Excluded economic studies
No economic evidence was identified for this review. See supplementary material 2 for further information.
Appendix K. Research recommendations – full details
Tables
Table 1Summary of the protocol (PICO table)
| Population | Women at increased risk of familial ovarian cancer |
|---|---|
| Intervention | Medicines:
|
| Comparison | In comparison with:
|
| Outcome | Critical
|
NSAIDS: non-steroidal anti-inflammatory drugs
Table 2Summary of included studies
| Study | Population | Intervention | Comparison | Outcomes |
|---|---|---|---|---|
|
Case-control USA |
N total=130 women with a family history of ovarian cancer n=31 women with epithelial ovarian cancer, n=16 used oral contraceptive and n=15 did not use it Age reported for all cases of ovarian cancer in the cohort (n=283): age mean (SD): not reported. Age by category (years): 20-29=7%, 30-39=11%, 40-49=40%, 50-54=42% n=99 controls, n=52 used oral contraceptive and n=47did not use it Age reported for all controls in the cohort (n=1929): age mean (SD): not reported. Age by category (years): 20-29=5%, 30-39=12%, 40-49=43%, 50-54=40% | Oral contraceptive use | No oral contraceptive use |
|
|
IPD meta-analysis USA |
N=7074 women with a family history of ovarian cancer n=1446 daily aspirin use n=5628 no daily aspirin use Age by category of aspirin use for the whole cohort reported (mean (SD), years): aspirin use = 63.4 (5.3), no aspirin use = 62.21 (5.39) | Daily aspirin use | No daily aspirin use |
|
|
IPD meta-analysis USA |
N=505404 Participants identified from 9 cohort studies and 8 case-control studies. Age mean (SD): ranged from 46 to 68.2 years in the cohort studies (SD not reported) and the median ranged from 56.2 to 60.7 years in the cases in the case-control studies. Not reported for the controls. | Frequent aspirin use (aspirin use for ≥6 days/week or ≥28 days/month and for a duration of ≥6 months) | Non-frequent aspirin use (no less frequent use than intervention group) |
|
|
IPD meta-analysis USA |
N=11135 Participants identified from 8 case-control studies Age mean (SD): not reported. Age, median (IQR): 58 (50-66) years for cases and 57 (49-65) years for controls | Frequent aspirin use (daily or almost daily use of aspirin for ≥6 months) | Non-frequent aspirin use (less frequent use than intervention group) |
|
|
Case-control Multinational, Canada |
N total=3223 women with BRCA1/2 mutation n=799 women with invasive ovarian cancer Age at questionnaire* (median (range), years): 53 (27-81) n=2424 controls Age at questionnaire* (median (range), years): 53 (33-82) *age at questionnaire and not cancer diagnosis because the latter is not applicable here for the control group | Oral contraceptive use | No oral contraceptive use |
|
|
Cohort USA |
N total=5062 women with a family history of ovarian cancer n=51 women with ovarian cancer n=5011 controls Age by category of oral contraceptive use duration for the whole cohort reported (median (range), years): 1-4 years=59 (55-64), 5-9 years=59 (55-64), >=10 years=60 (56-64) | Oral contraceptive use | No or <1 year oral contraceptive use |
|
|
Systematic review of observational studies Netherlands |
N=21,425 in 10 studies Women with BRCA1 or BRCA2 pathogenic mutations Age mean (SD): not reported. Age range: 20 to 93 years | Oral contraception pill | No oral contraception |
|
|
Case-control Multinational |
N total=714 women with BRCA1 mutation n=154 women with ovarian cancer and a previous history of breast cancer Age at diagnosis of ovarian cancer (mean (range), years): 51.4 (35-75) n=560 controls (women with a history of breast cancer) Age at diagnosis of ovarian cancer (mean (range), years): not applicable; age at diagnosis of breast cancer (mean (range), years):43 (26-68) | Oral contraceptive use | No oral contraceptive use |
|
IPD: individual patient data; SD: standard deviation.
Final
Evidence review underpinning recommendations 1.7.1 to 1.7.4 and research recommendation 6 in the NICE guideline
These evidence reviews were developed by NICE
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.