Studies Put Kibosh On Statins For Breast Cancer Prevention

New data from the Women’s Health Initiative dash cold water on the idea that statin therapy reduces breast cancer risk.

The updated WHI findings showed no association between prior statin use and breast cancer risk in nearly 155,000 postmenopausal study participants followed prospectively for an average of 10.8 years.

Indeed, the annualized rate of breast cancer was 0.42% in 11,584 statin users and 0.42% in nonusers in this analysis of 7,430 first cases of invasive breast cancer, Dr. Pinkal Desai reported at the San Antonio Breast Cancer Symposium.

Statin potency, duration of use, lipophilicity versus hydrophilicity – none of those factors had any impact, added Dr. Desai of Providence Hospital Medical Center in Southfield, Mich.

In commenting on Dr. Desai’s WHI update at a session on statins and breast cancer risk, Dr. Vered Stearns noted that the new data represent quite a turnabout, since an earlier report from the WHI was one of the major initial triggers of interest in the notion that statins might protect against breast cancer.

That report (J. Natl. Cancer Inst. 2006;98:700-7) analyzed 4,383 cases of invasive breast cancer among study participants followed for a median of 6.7 years. It showed no reduction in breast cancer risk in association with statins overall; however, there was an 18% reduction in risk (P =.02) among users of lipophilic statins, including simvastatin, lovastatin, and fluvastatin. With longer follow-up and more cases, however, that earlier benefit is gone, observed Dr. Stearns of Johns Hopkins University, Baltimore.

Moreover, a new meta-analysis has put a further damper on the hypothesis that statins protect against breast cancer, she continued. The meta-analysis included 13 published cohort and 11 case-control studies with more than 2.4 million participants, including 76,759 breast cancer patients. The investigators, from the National Institute of Pharmaceutical Education and Research in Punjab, India, found that neither statin use overall nor long-term statin therapy affected breast cancer risk (Breast Cancer Res. Treat. 2012;135:261-9).

Dr. Desai noted that the latest WHI findings do contain one glimmer of hope regarding statins and breast cancer: In a multivariate analysis, women on simvastatin were 13% less likely to develop breast cancer than statin nonusers after adjustment for demographic factors, body mass index, smoking, alcohol intake, family history, age at menarche and at first birth, NSAID use, dietary fat, physical activity, and mammography within the past 2 years. However, this trend toward reduced breast cancer risk with simvastatin therapy didn’t achieve statistical significance.

Statins are safe and cheap, and multiple products are readily available. But in light of the discouraging new epidemiologic data, Dr. Stearns declared "I think that the effects of statins as single agents are modest at best. There’s quite a good rationale, though, for prospective studies of them in combination with standard hormonal therapy, chemotherapy, and radiation therapy, as well as with novel cancer treatment agents."

She added that the statins remain worthy of research interest because many of their pleomorphic cellular effects are antineoplastic. The drugs inhibit the mevalonate pathway, down-regulate metalloproteinases, inhibit Rho and Ras activation, decrease CD44 cells, and increase PTEN antibodies, all of which are salutary from an anticarcinogenesis standpoint.

Dr. Desai and Dr. Stearns reported having no financial conflicts of interest.