Do statins cut breast cancer recurrence?
“A daily dose of drugs designed to lower cholesterol could also slash the risk of breast cancer recurring,” the Daily Mail reported today.
The news is based on the findings of a large Danish study that looked for an association between the use of statins and the recurrence of breast cancer. Researchers followed 18,769 women, for an average of 6.8 years, who had previously been diagnosed with invasive breast cancer. Of these, 17% had been prescribed statins at some point. Compared to women who did not use statins, women who took simvastatin and other “lipophilic” (fat-soluble) statins were less likely to have breast cancer that reoccurred. Those who took “hydrophilic” (water-soluble) statins did not have a reduced risk. However, this type of statin was used by only 6% of the statin users, which limits the strength of this finding.
This type of study can only find associations, and further studies would need to confirm that the lower risk of recurrent breast cancer is caused by lipophilic statins. The findings do not mean that taking a statin provides any protection against developing breast cancer in the first place. Without further study, women who have had breast cancer but who have no medical reason to use statins should not be encouraged to take the medication to try to prevent their cancer from coming back.
Where did the story come from?
The study was carried out by researchers from Brigham and Women’s Hospital, Harvard Medical School and Boston University School of Medicine in the US, and Aarhus University Hospital and Aalborg Hospital, Denmark. It was funded by Klinisk Institute of Aarhus University Hospital, the United States National Cancer Institute at the National Institutes of Health, the Danish Cancer Society, the Karen Elise Jensen Foundation, and the Congressionally Directed Medical Research Programs. The study was published in the peer-reviewed Journal of the National Cancer Institute.
The Daily Mail’s report was mainly accurate.
What kind of research was this?
This cohort study examined the association between statin use and breast cancer recurrence in a cohort of Danish women diagnosed with invasive breast cancer. Statins are a class of drug that lower cholesterol levels, and are usually prescribed to prevent cardiovascular disease.
The study’s design is appropriate for finding associations between factors. However, it cannot show that one thing causes another. The potential use of statins as an additional treatment to help prevent recurrent breast cancer would need to be assessed in a randomised controlled trial.
What did the research involve?
The researchers enrolled all female residents of Denmark diagnosed with stage I-III invasive breast cancer from 1996 to 2003 (18,769 women). Data on tumours, treatment and patient characteristics were collected. Women were followed for an average (median) of 6.8 years (maximum 10 years) after initial diagnosis, and follow-up examinations were performed every 3-6 months for the first five years after diagnosis and then annually.
Statin use was determined from the national electronic pharmacy database, which recorded filled statin prescriptions. The researchers analysed statin usage on a yearly basis. Women were defined as statin users if they had been prescribed statins at least once that year, and non-users if they had not.
The use of a lipophilic (fat-soluble) statin was defined as exclusive use of simvastatin, lovastatin, fluvastatin or cerivastatin. Lipophilic statins were used by 2,524 women, 92% of whom were prescribed simvastatin. The use of a hydrophilic (water-soluble) statin was defined as exclusive use of atorvastatin, pravastatin or rosuvastatin. Hydrophilic statins were used by 206 women.
The researchers then looked at the association between statin use and recurrent breast cancer, after they had adjusted the data to account for the women’s age and menopausal status at diagnosis, the type of tumour, treatment, hormonal therapy before diagnosis and other medications that the women were taking.
What were the basic results?
Over the median 6.8 years of follow-up, there were 3,419 breast cancer recurrences in this cohort of 18,769 women.
Of the cohort, 3,282 women were prescribed a statin at some point during the follow-up. The median length of time that the statin was prescribed for was four years.
Over the follow-up period:
- The adjusted recurrence risk of breast cancer among women who did not use statins was 0.302 (3,170 recurrences).
- The adjusted recurrence risk of breast cancer among statin users was 0.207 (249 recurrences).
- The adjusted recurrence risk of breast cancer among women who were exclusively prescribed a lipophilic statin was 0.194 (182 recurrences).
- The adjusted recurrence risk of breast cancer among women who were exclusively prescribed a hydrophilic statin was 0.350 (39 recurrences).
- Lipophilic statin users had a reduced rate of recurrence compared with non-users (10-year adjusted hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60 to 0.89).
Users of hydrophilic statins had approximately the same risk of breast cancer recurrence as non-users.
Compared with non-users of any statin, users of simvastatin (the most commonly prescribed lipophilic statin) had a further reduced risk of recurrence (10-year adjusted HR 0.70, 95% CI 0.57 to 0.86).
The adjusted 10-year risk difference between women prescribed simvastatin compared with non-users was -0.10 (95% CI -0.11 to -0.08). This means that exclusive simvastatin users had approximately 10 fewer breast cancer recurrences per 100 women after 10 years of follow-up.
To confirm that the association observed was due to simvastatin and was not affected by the medical condition that led to the women taking statins, the researchers compared the risk of recurrence in exclusive simvastatin users and people who received a different class of statins (hydrophilic statins). Again, they found that simvastatin was associated with a reduced risk of breast cancer recurrence (10-year adjusted HR 0.55, 95% CI 0.35 to 0.85).
How did the researchers interpret the results?
The researchers concluded that “simvastatin, a highly lipophilic statin, was associated with a reduced risk of breast cancer recurrence among Danish women diagnosed with stage I-III breast carcinoma, whereas no association between hydrophilic statin use and breast cancer recurrence was observed.”
In this cohort study, use of a lipophilic statin (including simvastatin, the most commonly prescribed of the statins) was associated with a reduced risk of recurrent breast cancer in women with invasive breast cancer.
The researchers also investigated the association between the exclusive use of simvastatin and the risk of recurrent breast cancer, and found that use of simvastatin reduced the risk of recurrent breast cancer compared to no statin treatment or treatment with a hydrophilic statin. Use of a hydrophilic (water-soluble) statin, including atorvastatin, pravastatin or rosuvastatin, was not found to be associated with reduced risk, though the strength of this result is limited by the small proportion of statin users (only 6%) who used this type of statin. The trial also has numerous limitations, including the fact that it is not known whether the women who were prescribed statins actually took the drugs. Also, the study was not able to adjust for certain potential confounders that may have affected the risk of breast cancer recurrence, such as the women’s body mass index.
This finding is worthy of further study to investigate whether the use of lipophilic statins directly reduces the risk of recurrent breast cancer. Further investigation into why these types of statins have this effect is also warranted.
On its own, this study can only demonstrate an association and does not provide conclusive evidence that statins reduce the risk of breast cancer recurrence. A randomised controlled trial would be needed to more accurately determine whether taking a statin reduces the risk of recurrence in women previously diagnosed with breast cancer. However, the ethics of using statins in women with no cardiovascular reason for taking them would need to be considered in such a trial.
The current study does not provide any evidence that taking a statin protects against developing breast cancer in the first place. Without further study, women previously diagnosed with breast cancer and who have no cardiovascular risk factors should not be encouraged to start taking statins to try to prevent cancer recurrence.
- Ahern TP, Pedersen L, Tarp M et al. Statin Prescriptions and Breast Cancer Recurrence Risk: A Danish Nationwide Prospective Cohort Study. Journal of the National Cancer Institute (2011) 103 (19): 1461-1468.
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