Epidemiology of epithelial ovarian cancer Webb, Penelope M; Jordan, Susan J
Best practice & research. Clinical obstetrics & gynaecology,
05/2017, Letnik:
41
Journal Article
Recenzirano
Abstract Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates ...are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer.
Globally, ovarian cancer is the eighth most common cancer in women, accounting for an estimated 3.7% of cases and 4.7% of cancer deaths in 2020. Until the early 2000s, age-standardized incidence was ...highest in northern Europe and North America, but this trend has changed; incidence is now declining in these regions and increasing in parts of eastern Europe and Asia. Ovarian cancer is a very heterogeneous disease and, even among the most common type, namely epithelial ovarian cancer, five major clinically and genetically distinct histotypes exist. Most high-grade serous ovarian carcinomas are now recognized to originate in the fimbrial ends of the fallopian tube. This knowledge has led to more cancers being coded as fallopian tube in origin, which probably explains some of the apparent declines in ovarian cancer incidence, particularly in high-income countries; however, it also suggests that opportunistic salpingectomy offers an important opportunity for prevention. The five histotypes share several reproductive and hormonal risk factors, although differences also exist. In this Review, we summarize the epidemiology of this complex disease, comparing the different histotypes, and consider the potential for prevention. We also discuss how changes in the prevalence of risk and protective factors might have contributed to the observed changes in incidence and what this might mean for incidence in the future.
Most women with ovarian cancer have a poor prognosis, but studies have reported an association between statin use and improved survival. We investigated the potential survival benefit of statins in ...women with ovarian cancer using data from the Ovarian cancer Prognosis and Lifestyle study, a prospective study of Australian women aged 18 to 79 years, diagnosed with ovarian cancer from 2012 to 2015 and followed for 5 to 8 years. We obtained information from patient‐completed questionnaires and medical records. We defined exposure based on prediagnosis use, as most women used statins continuously (prediagnosis and postdiagnosis) and few started using statins postdiagnosis. We measured survival from date of first treatment (surgery or neoadjuvant chemotherapy) until date of death or last follow‐up. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for potential confounders. To reduce bias due to confounding by indication, we also applied inverse probability of treatment weighting (IPTW). Of 955 eligible women, 21% reported statin use before diagnosis. Statin users had a slightly better survival (HR = 0.90, 95% CI = 0.70‐1.15) that was driven by lipophilic statin use (HR = 0.82, 95% CI = 0.61‐1.11), with no association for hydrophilic statins (HR = 1.04, 95% CI = 0.72‐1.49). The IPTW model weighted to all women with ovarian cancer also suggested a possible reduction in mortality associated with lipophilic statins (HR = 0.80, 95% CI = 0.54‐1.21). In analyses restricted to women with hyperlipidaemia, the HRs were further from the null. Our findings are consistent with previous evidence, suggesting that lipophilic statins might improve ovarian cancer survival. Further investigation, in larger cohorts, or preferably in a randomised trial, is required.
What's new?
Ovarian cancer generally has a poor prognosis. Some previous studies have indicated that statins may improve survival, but these may have been subject to various forms of bias. In the present study, the authors used statistical methods that minimize bias to analyze data from a prospective Australian trial. They found that lipophilic statins may indeed enhance survival for ovarian cancer patients, particularly for women with hyperlipidaemia. Hydrophilic statins had no effect on survival. Further investigations to evaluate lipophilic statins in larger cohorts, preferably randomized clinical trials, are recommended.
Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer disease and Alzheimer disease–related dementias by 2025. To help inform the research agenda ...toward achieving this goal, the NIH hosts periodic summits that set and refine relevant research priorities for the subsequent 5 to 10 years. This proceedings article summarizes the 2016 Alzheimerʼs Disease–Related Dementias Summit, including discussion of scientific progress, challenges, and opportunities in major areas of dementia research, including mixed-etiology dementias, Lewy body dementia, frontotemporal degeneration, vascular contributions to cognitive impairment and dementia, dementia disparities, and dementia nomenclature.
Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and ...environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second‐hand), dietary factors (low intake of fruit, non‐starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk.
What's new?
Cancer is the leading cause of death in Australia. Yet many of these deaths could be prevented if known causes were avoided. In this study, the authors estimated the number and fraction of cancer deaths and cancer cases in Australia attributable to modifiable factors. They found that 38% of all cancer deaths and 33% of cancer cases could be attributed to 20 factors. Tobacco smoke was the leading cause of cancer death, followed by dietary factors, overweight/obesity, infections and solar ultraviolet radiation.
Ovarian cancer is usually diagnosed at an advanced stage when five-year relative survival is <50%. Therefore, strategies to improve survival are required. Studies suggest associations between common ...chronic disease medications such as metformin, statins, beta-blockers, aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) and improved cancer survival. We aimed to review the evidence for a possible relation between these medications and survival among women with ovarian cancer.
We conducted four systematic reviews and evaluated the risk of bias in the included studies. Where possible, we calculated pooled hazard ratios (pHR) and 95% confidence intervals (CI), excluding studies considered to have the potential for immortal time bias (ITB) which, in practice, was the major source of bias.
We identified 36 studies evaluating one or more of the medications (metformin n = 8, statins n = 12, beta-blockers n = 11, aspirin and/or NA-NSAIDs n = 9). We rated 21 studies as ITB-free. The meta-analysis of the ITB-free studies suggested improved survival in statin users compared to non-users (pHR: 0.76, 95%CI: 0.68–0.85), but no overall survival benefit associated with use of metformin, beta-blockers, aspirin or NA-NSAIDs. The pooled result of two studies did, however, suggest a possible association between perioperative beta-blocker use and improved survival. Studies considered to have potential ITB were more likely to report survival benefits associated with these medications.
Statin use is associated with better ovarian cancer survival but further study, preferably a clinical trial, is required. There are insufficient data to draw conclusions regarding metformin, beta-blockers, aspirin and NA-NSAIDs.
•Observational studies suggest better ovarian cancer survival among statin users; confirmation requires a randomised trial.•There is little evidence for beta-blockers, but a possible association with perioperative use requires further study.•There is insufficient evidence regarding the association between metformin, aspirin/NSAIDs and ovarian cancer survival.•Studies likely to have immortal time bias were more likely to report a survival benefit for the use of these medications.
Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that ...inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study.
Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects.
Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery.
Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.
Objective: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia.
Design: Analysis of routinely ...collected death certificate and corresponding population data from the Australian Bureau of Statistics.
Setting: Population‐based, Australia‐wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010.
Main outcome measures: Absolute and relative excess of cancer deaths in regional and remote areas.
Results: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% CI, 8187–9572). For men, the age‐standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997–2000 to 1.11 in 2006–2010. For women, they increased from 1.01 in 1997–2000 to 1.07 in 2006–2010. The age‐standardised cancer death rate in regional and remote areas (annual percentage change APC, − 0.6%; 95% CI, − 0.8% to − 0.4%) is decreasing more slowly than in metropolitan areas (APC, − 1.1%; 95% CI, − 1.3% to − 1.0%).
Conclusions: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising — we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research.
Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 ...studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors.
Nine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2).
Overall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design (
= .48) or histotype (
= .60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all
-heterogeneity > .05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90).
This study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.
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