Painkillers and breast cancer

Wednesday October 8 2008

“Using painkillers can cut risk of breast cancer by one fifth,” reports The Daily Telegraph . A review of studies has investigated the links between the use of aspirin and other painkillers, such as ibuprofen, and the risk of breast cancer. The review found that “using ibuprofen alone could reduce the risk by 21%, while aspirin cut the chances of developing the cancer by 13%”, the newspaper says.

The possibility that anti-inflammatory drugs could protect against cancer has frequently been a topic of research. This comprehensive review of studies found evidence of some protective effect, but the possible biological mechanisms for this require further investigation. However, aspirin and other painkillers are not without risks in themselves. Regular use can increase the risk for inflammation in the stomach and upper digestive system, causing ulcers and bleeding, and the elderly are most at risk of this. Concerned women who are thinking about taking painkillers on a regular basis, solely for protection against breast cancer, should discuss their individual risk with a medical professional.

Where did the story come from?

Dr Bahi Takkouche and colleagues of University of Santiago de Compostela in Spain and University of British Columbia in Canada, carried out this research. The study was funded by CIBER en Epidemiología y Salud Pública and the Canadian Institutes of Health Research. It was published in the peer-reviewed Journal of the National Cancer Institute .

What kind of scientific study was this?

This was a systematic review with meta-analysis, in which the authors aimed to collate the evidence for the association between breast cancer and the use of non-steroidal anti-inflammatory drugs (NSAIDs).

A search was made of the computer databases Medline, EMBASE and LILACS for all case-control or cohort studies carried out up until July 2008 that included the search terms ‘breast cancer’ (tumours or neoplasms) and ‘NSAIDs’ or named drugs of this category, e.g. aspirin, ibuprofen, naproxen, etc. They also examined abstracts of studies presented at relevant meetings, using another database (ISI Proceedings) and looked through the reference list of every article retrieved. Only published studies were considered, but there were no restrictions based on the language of publication.

Included studies had to have:

  • Presented original study data.
  • Defined breast cancer as their primary outcome of interest.
  • Defined NSAID use as the primary exposure of interest.
  • Provided calculations of relative risk (or enough data to calculate this).

Researchers used a prepared questionnaire to extract all relevant information from the individual studies, and carried out a thorough assessment of study quality. The researchers then pooled the results of the relevant studies to examine the association between NSAID use and breast cancer. Where studies looked at different levels of exposure to NSAIDs, the researchers used results for the highest dose and longest duration of NSAID use in their analyses.

The researchers then combined the study results using statistical methods, taking into account any differences between study methods and results. They also carried out analyses to account for the possibility that some studies assessing the link between NSAIDs and breast cancer may have not been published, and that these unpublished studies may have different results to the published studies.

What were the results of the study?

Thirty-eight relevant studies were identified (18 cohort, 16 case-control and three case-control within a cohort and one clinical trial – these final four were grouped into ‘cohort’), carried out in five different countries and involving a total of 2,788,715 women.

Combining the results from all 38 studies, the use of NSAIDs was associated with a 12% reduction in risk of breast cancer (relative risk 0.88, 95% confidence interval [CI] 0.84 to 0.93). The result remained significant in separate analyses of the 22 cohort and 16 case-control studies and with separate analysis of high- and low-quality studies.

Analysis of all studies examining aspirin use only (27 studies) found a 13% decreased risk of breast cancer (relative risk 0.87, 95% CI 0.82 to 0.92). Analysis of all studies examining ibuprofen use only (8 studies) found a 21% decreased risk of breast cancer (relative risk 0.79, 95% CI 0.64 to 0.97).

What interpretations did the researchers draw from these results?

The authors conclude that their meta-analysis has found an overall decreased risk of breast cancer with NSAID use. They call for further research into the possible biological mechanisms behind this relationship.

What does the NHS Knowledge Service make of this study?

This comprehensive review of studies has found evidence of some protective effect of NSAIDs against breast cancer. As the authors acknowledge, the possible biological mechanisms for this require more investigation. Some limitations to consider:

  • The review does not provide specific detail on NSAID use in the individual studies (e.g. duration of use, dosage or whether the women were taking the drugs for a particular reason, e.g. for heart disease or arthritic conditions). Also, there was no detail about how the breast cancer outcome was determined (e.g. whether it was histologically confirmed breast cancer, by invasiveness, stage, etc.).
  • The individual studies varied in the possible confounding factors for breast cancer risk that they adjusted for (e.g. age, smoking, family history, oestrogen use, menopausal status etc.). As these were all cohort and case-control studies, these factors may have differed between the women who were and were not taking NSAIDs, and this might have affected the risk of breast cancer and the study results. Additionally, other drugs that may have been taken alongside the NSAIDs could have had an effect on breast cancer risk.
  • In case-control studies, information about the use of NSAIDs would have been collected after the diagnosis of breast cancer, and this may have led to biased recall about the previous use of drugs. The authors highlight this, as there was a slightly greater reduction in the risk of breast cancer with NSAID use seen in the separate analysis of the case-control studies compared with that of cohort studies.  
  • Randomised controlled trials would be the most reliable method of balancing other risk factors and assessing the effect that regular use of NSAIDs had on the risk of developing breast cancer. However, such a trial may not be practical (considering the large numbers of volunteers required and extended length of follow-up). Safety issues would also have to be considered.
  • The study has not investigated and provides no evidence for any effect of taking aspirin or NSAIDs in women who already have, or have had, breast cancer.

It is important to be aware that aspirin and other NSAIDs are not without risks in themselves. Regular use of either increases the risk for inflammation in the stomach and upper digestive system, including ulcers and bleeding, with the elderly being most at risk of this complication. Breast cancer has a number of possible risk factors, such as age, smoking, family history and prolonged synthetic oestrogen use. Concerned women who are considering commencing aspirin or NSAIDs on a regular basis, solely for protection against breast cancer, should discuss their individual risk with a medical professional.

Analysis by Bazian
Edited by NHS Choices