Liam Davenport

June 10, 2015

CHICAGO — Statin use is associated with a significant reduction in cancer mortality, conclude two separate studies, one in women, the other in men. Both were presented here at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.

Specifically, statin use was associated with a 22% reduction in deaths from various cancer types in women and a 55% reduction in deaths from bone/connective tissue cancers. The study in men looked at statin use together with the antidiabetes medication metformin and found a 40% reduction in prostate cancer mortality, with the effect more pronounced in men with obesity/metabolic syndrome.

As for how such an effect is achieved, the researchers speculate that statins interfere with cell growth and metastasis by blocking cholesterol production, thereby affecting molecular pathways and the inflammatory response.

Statin Use Analysis of WHI Study Data

The results in women were presented by Ange Wang, BSE, from Stanford University School of Medicine, in California.

Dr Wang and colleagues examined data from the Women's Health Initiative, a 15-year research program involving postmenopausal women aged 50 to 79 years who were enrolled between 1993 and 1998 at 40 centers in the United States.

They determined the association between patients' never having used statins, current statin use, and past statin use, as well as the incidence and number of deaths from cancer among 146,326 women. The median follow-up period was 14.6 years.

The researchers took into account a number of potential confounding factors, including age, race/ethnicity, education, smoking, body mass index, physical activity, family history of cancer, and current healthcare provider.

Among the participants, there were 23,067 cases of incident cancer for which complete follow-up data were available. There were 7411 all-cause deaths, including 5837 deaths from cancer, 613 cardiovascular deaths, and 961 deaths from other causes. In all, 3152 cancer deaths were included in the analysis, of which 708 were among current statin users and 2443 among patients who had never used statins.

Multivariate analysis demonstrated that statin use was not associated with cancer incidence, and there was no association between past statin use and cancer mortality.

However, the researchers found that, compared with never having used statins, current statin use was associated with a significant reduction in cancer mortality, with an adjusted hazard ratio (aHR) of 0.78 vs never use (P < .0001). The association was unaffected by statin potency, lipophilicity/hydrophilicity, type, or duration.

Statin use was associated with significant reductions in deaths from breast (aHR = 0.60), ovarian (aHR = 0.58), colorectal (aHR = 0.57), digestive (aHR = 0.68), and bone/connective tissue cancers (aHR = 0.45), but not from lung cancer (aHR = 1.17).

Dr Wang noted that although the validity of the results is supported by the prospective nature of the study, the post hoc analysis means that causality cannot be established.

"Our study found that lipid-lowering medications, including statins, are associated with lower all-cancer mortality, and that might be related to the lower cholesterol levels induced by these medications," Dr Wang concluded.

"Given the widespread use and growing use of statins under the new guidelines and the high burden of cancer, our findings are promising in suggesting a potential intervention that may benefit cancer patients," she added.

It is notable, however, that the effect of statins does not persist after their use and that there is no impact on cancer incidence, she commented. Consequently, she noted that further studies of the effect of statin use on cancer are needed, including randomized, controlled trials and studies in men and in patients of other age groups and ethnicities.

Commenting on the study, Richard Roope, MD, from the cancer charity Cancer Research UK, emphasized that a causal relationship between cancer mortality risk and statin use was not demonstrated in the study and agreed that more research is required.

In a release, he cautioned that this research "doesn't prove that postmenopausal women should take statins to lower their risk of dying from cancer."

"We don’t know for sure if the link shown between a decreased risk of dying from cancer and statin use is due to the drugs themselves or some other reason," he added.

Reduction in Prostate Cancer Death

The other study, showing a reduction in prostate cancer mortality, was presented by Grace L. Lu-Yao, PhD, from the Rutgers Cancer Institute of New Jersey, in New Brunswick. Her team looked at use of both statins and metformin, a diabetes medication, because of hints seen in previous studies.

The researchers used Surveillance, Epidemiology and End Results–Medicare linked data to follow 22,110 patients diagnosed with high-risk prostate cancer, defined as a prostate-specific antigen (PSA) score of ≥20, a Gleason score of 8-10, or stage III or IV cancer.

Prescription drug exposure was collated from Medicare Part D event files, and Cox regression analysis was used to compare prostate cancer–specific mortality (PCSM) and covariates such as age, race, marital status, use of ADT, PSA and Gleason score at diagnosis, and comorbidity score.

There were 1365 deaths from prostate cancer between 2007 and the end of 2009. The majority of metformin users were also prescribed statins. Patients who took both statins and metformin (n = 1315) were more likely than other patients to have a comorbidity score of ≥2 and to have obesity/metabolic syndrome.

Patients who took metformin alone (n = 455) experienced no reduction in overall mortality or PCSM compared with those who used neither medication (n = 14,849; HR, 1.04 and 0.92, respectively).

However, patients who took both statins and metformin had a substantial reduction in both overall mortality and PCSM (HR, 0.66 and 0.57, respectively). A similar pattern was seen in patients who took statins alone (n = 4353; HR, 0.75 and 0.60, respectively).

The impact of combined statin and metformin therapy on overall mortality and PCSM was more pronounced in patients with documented obesity/metabolic syndrome, although the differences did not reach statistical significance.

Dr Lu-Yao concluded that, despite patients receiving combination therapy having more comorbidities and being more likely to have documented obesity/metabolic syndrome, statin and metformin therapy was associated with markedly better survival than patients taking metformin alone.

She suggested that, given that the majority of metformin users also take statins, the survival benefit observed in metformin users in the literature may be largely due to statin use.

This study was discussed, among other poster presentations, by Noel Clarke, MBBS, ChM, from the Salford Royal Hospital and the Christie, Manchester, United Kingdom.

He pointed out that the study was of relatively short duration and that only 6.2% of the patients died of prostate cancer.

Noting that the survival benefit appeared to be driven by statins alone, he suggested that the follow-up period was probably too short to show the impact of metformin, insofar as previous studies have shown that metformin needs to be taken for at least 3 years to have a survival benefit.

Several UK newspapers reported the statin studies, which had been highlighted in a press release issued by Cancer Research UK. In an interview with the Telegraph, Dr Clarke said: "The balance of evidence says that statins have an anticancer effect."

The study reported in abstract 1506 was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the US Department of Health and Human Services. No funding was declared with regard to the study reported in abstract 5018. The investigators have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstracts 1506 and 5018. Presented May 30, 2015.


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