October 5, 2018

expert reaction to report on the use of analgesics and risk of ovarian cancer

Research published in JAMA Oncology appears to show a reduced risk of ovarian cancer among regular users of of low-dose aspirin.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine (LSHTM), said:

“This paper comes from two very well known studies that have followed women over many years. The analysis is good but the limitations in the data mean that the findings should be treated with caution. They have two groups followed for different amounts of time, but they include 93,664 women in the, who were followed up from 1980 to 2014, and 111,834 in the second, followed from 1989 to 2015.  The over 205,000 women were followed for an average of 17.8 years (data derived from the paper).

“The authors are not explicit, but it is clear that they are looking at a very rare disease in this population. They have a total of 3.66 million person-years of observation. This is equivalent to 3.66 million women followed for 1 year. There were a total of 1054 ovarian cancers, so this is equivalent to 29 per 100,000 patient years. The increases in the rates are generally small and are vulnerable to the possibility of unmeasured factors explain the small differences.

“The results are slightly puzzling in relation to aspirin with low-doses showing a decreased risk and higher doses showing an increased risk. This could be an indication that unmeasured factors are an explanation for the findings.

“The authors say clearly that those at high cardiovascular risk who take low-dose aspirin should not be concerned about an increase in the risk of ovarian cancer. Other pain-relieving drugs (Non-steroidal anti-inflammatory drugs- NSAIDs) and aspirin at higher doses do not have this reassurance for long-term use. However, the risk for any particular individual, even if these findings are correct, is not high, and they may not be correct.”

Dr Mangesh Thorat, Deputy Director (Clinical) – Cancer Prevention Trials Unit (Barts CTU), Centre for Cancer Prevention, Queen Mary University of London, said:

“The study by Barnard and colleagues uses data from well-known Nurses’ Health Study (NHS) cohorts to study effect of use of aspirin, Non-aspirin NSAIDs (NANSAIDs), and acetaminophen on the risk of epithelial ovarian cancer. Nurses’ Health Study (NHS) cohorts are well-organised and regularly updated cohorts that have been followed up for a long period of time, and hence continue to add to our knowledge. Until publication of this well-conducted research, limited weak evidence from case-control studies indicated beneficial effect of aspirin on ovarian cancer. This study adds to that evidence, at the same time suggesting that any benefit may be restricted to regular prolonged use of low-dose (75-100mg/d) Aspirin; higher doses of Aspirin do not reduce risk of ovarian cancer, while long-term use of NANSAIDs appears to be associated with an increase in the risk of ovarian cancer.

“Recent evidence suggests a complex relationship between weight, height and aspirin’s dose as far as cardiovascular effects are concerned whereas optimum cancer prevention dose has always been an open question. Although Barnard and colleagues accounted for BMI in their analyses, their analyses did not explore in detail the relationship between weight, height and aspirin’s dose.

In summary, this well-conducted study adds to the evidence that prolonged regular use of low-dose aspirin may reduce risk of ovarian cancer, but overall evidence still remains insufficient to recommend aspirin use specifically for ovarian cancer prevention. The study also raises a caution, although nothing beyond an observed association, about long-term use of other NSAIDs.”

Dr June Raine, Director of MHRA’s Vigilance and Risk Management of Medicines Division, said:

“NSAIDS are effective in the treatment of pain and fever and are recommended to be used at the lowest effective dose and the shortest duration necessary, as directed in the information provided with the medicine.

“It is important that aspirin should be used as directed in the information provided with the medicine or as directed by a doctor.”

“All medicines, including those bought over-the-counter, must be used responsibly and as advised in the information provided with the medicine”

“The safety of all medicines is of paramount importance and we will look carefully at the new study to see if there are any implications for the current product information.”

Prof Justin Stebbing, NIHR Research Professor of Cancer Medicine and Medical Oncology, Imperial College London, said:

“This is a well powered big study and one that would fulfil any definition of a quality study, adding to the literature that a low dose of aspirin may reduce the risk of cancer by having anti-inflammatory properties. As far as I know it’s the first study too that in detail looks at the associations between type, timing, frequency, quantity, and duration of analgesic/pain-killer use with risk of ovarian cancer by using regularly updated exposure information. But, they did not observe associations between total aspirin use and ovarian cancer risk, only low dose aspirin. It is possible that use of non-aspirin NSAIDs and use of acetaminophen may be associated with increased risk but there are so many confounding factors it’s so hard to say there’s causation i.e. one cannot say that paracetamol use is associated with an increased risk of ovarian cancer. When this paper was written, I don’t think the authors knew the results of the recent NEJM papers so were able to evaluate these data independently. Of course no study is perfect, for example this only included women aged 29-59 and didn’t ask why they took analgesics, but it’s still a very good study.”

“These sorts of studies along with the NEJM one just published help us understand the role, benefits and risks in healthy people, and those with disease, as we strive to improve both quantity and quality of life.”

‘Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies’ by Mollie Barnard et al. was published in JAMA Oncology at 16:00 UK time on Thursday 4th October. 

Declared interests

Prof Stephen Evans: No conflicts of interest

Dr Mangesh Thorat: Dr. Thorat was one of the organisers of GI Cancer Prevention conference in 2014 that received educational grant from Bayer, makers of Aspirin.

None others received.