WASHINGTON – Statin use – both before and after a diagnosis of breast cancer – was associated with up to a 66% reduction in the risk of dying from that cancer, a large database study has concluded.

Investigators reported that the risk reduction was consistent even after controlling for age, tumor stage and morphology, and primary treatment choice, Dr. Teemu Murtola said during an interview at the annual meeting of the American Association for Cancer Research.

"We saw that there was clearly a dose-dependent reduction in the risk of breast cancer mortality among statin users," who comprised 13% of the more than 31,000 women in the study, said Dr. Murtola, an epidemiologist at Johns Hopkins University in Baltimore. "The association held for both localized and metastatic tumors. There really appears to be something going on here, and it’s certainly a reason for further study."

During the follow-up, 6,011 women died; 3,169 deaths were due to breast cancer. The death rate among users was significantly lower than it was among nonusers (7.5% vs. 21%). In the adjusted analysis, statin users were 67% less likely to die than were nonusers with localized disease (hazard ratio, 0.33). Among those with metastatic disease, statins conferred a 48% decreased risk of death (HR, 0.52).

All of the statins investigated in the study cohort were associated with a significantly decreased risk of breast cancer death, including simvastatin (HR, 0.47), atorvastatin (HR, 0.27), fluvastatin (HR, 0.35), and pravastatin (HR, 0.50).

The retrospective study looked at statin use and breast cancer mortality among 31,114 women with breast cancer who were diagnosed in Finland during 1995-2003. All of the patients were included in the Finnish Cancer Registry. The country’s national health database also contained detailed information on statin use and other health indicators. The data on statins included the date of each prescription purchase, the numbers of refills, the dosage, and the number of pills in each refill.

Breast cancer data included the date of diagnosis, stage (local, lymph-node positive or metastatic), morphology, primary treatment choice (surgery, radiation, chemotherapy, hormonal therapy, or other), and the date and cause of death.

Follow-up started at the time of diagnosis and continued until death or the common closing date of Dec. 31, 2003, whichever came first. Median follow-up was about 3 years, but ranged from less than 1 year to 9 years.

Statin users accounted for 13% of the cohort (4,169); the remainder never used the drugs. Women who took the medications were significantly older than nonusers (64 years vs. 58 years), and more likely to have had surgery as a treatment (96% vs. 92%). They were also more likely to have undergone radiation (55% vs. 54%), but significantly less likely to have had chemotherapy (15% vs. 24%) or hormonal therapy (20% vs. 25%). Metastatic cancer was significantly less common among statin users – 4% vs. 7%. These differences may reflect an early identification of breast cancer among users, perhaps because they were visiting a physician more frequently for lipid monitoring, Dr. Murtola said. However, the multivariate analysis controlled for all these differences, including metastatic and local disease.

Dr. Murtola then investigated the mortality effects of both pre- and postdiagnostic statin use.

Compliance was high among women who started the drugs before their breast cancer diagnosis, with 85% continuing until the end of follow-up. Compared with nonusers, women who used statins for up to 490 days were 46% less likely to die of local disease and 30% less likely to die from metastatic disease.

Those who took the drugs for 491 days or more before diagnosis were 66% less likely to die from local disease and 40% less likely to die from metastatic disease.

There was no such clear, dose-dependent relationship between mortality risk and statins taken after diagnosis, Dr. Murtola said. But, he added, low compliance could have masked any benefit. "Only 14% of those who started statins after diagnosis continued to take them until the end of the follow-up period," he said. "When we limited the analysis to those who were compliant until the end of their follow-up, we saw a very similar dose-dependent risk reduction in breast cancer mortality."

In vitro studies suggest that statins could have a direct effect on breast cancer cells, he said. They seem to block the mevalonate pathway – a process involved in the manufacture of cholesterol, and also key to cell metabolism. Cells with abnormally high metabolic rates – like breast cancer cells – could be particularly vulnerable to this action, he said.

"I think that because the drugs target this pathway their impact extends beyond cholesterol. It’s certainly worth further study."

Dr. Murtola had no financial disclosures.

msullivan@frontlinemedcom.com

Study suggests statin use decreases breast cancer mortality