Date Posted, by DCP Staff
Two recent publications focus on widely used treatments for other diseases to evaluate possible roles in the prevention of cancer. One looked at the potential of statins, a common heart disease drug, to prevent gynecologic cancers, and the other examined whether metformin, a drug for type 2 diabetes, could reduce the risk for breast cancer development. In both studies, investigators relied on a growing understanding of the anti-cancer mechanisms of each drug to assess efforts to repurpose them for cancer use.
Statins, frequently prescribed cholesterol-lowering drugs for protecting against heart disease, carry anti-inflammatory and other anti-cancer effects that researchers theorize might help prevent ovarian and endometrial cancers. Similarly, the drug metformin, widely prescribed for adults with type 2 diabetes, carries anti-cancer properties that could inhibit cancer development and holds promise for reducing breast cancer risk in some women.
Although it’s not a new concept, drug-repurposing has emerged over the past several decades as an effective strategy for maximizing a drug’s therapeutic value after the Food and Drug Administration has approved its safety and efficacy for another use. This innovative approach is considered efficient, timesaving, and less costly than the traditional drug-discovery process, which can take years to complete.
A Case for Statins in Gynecologic Cancer Prevention
In the first publication, investigators summarized both preclinical and clinical data supporting a potential role for statin drugs in preventing gynecologic cancers. Ovarian and endometrial cancers carry a high mortality rate and have few nonsurgical options, making it “imperative to develop more suitable options” for women diagnosed with these diseases, the researchers wrote in a commentary in Cancer Prevention Research.
The investigators found that statins’ anti-invasive and anti-inflammatory effects support a repurposed cancer preventive use. In the laboratory, these drugs have also demonstrated an ability to quell unruly cell growth and aid in apoptosis, the process by which the body eliminates cells containing errors in genes that can give rise to cancer. According to the Centers for Disease Control and Prevention, nearly 25 million adults have high total cholesterol, and only about half of those who could benefit from cholesterol-lowering medicines are taking them.
But before statins can be widely used for preventing gynecologic cancers, researchers must gain a better understanding of risk reduction in the most vulnerable populations, they wrote, given that high-risk groups should be targeted first “to effectively balance risk/benefit of medications repurposed for cancer prevention.”
Among the remaining hurdles: difficulties enrolling sufficient numbers of patients with risk of these rare cancers into future clinical trials, determining whether effects seen in observational studies can be translated into clinical use, and the need to evaluate the impact of various statins on the different subtypes seen in both ovarian and endometrial cancers.
According to the researchers, the process of evaluating the potential use of statins will require steps that parallel that of researching aspirin use to prevent colorectal cancer: identifying an optimal age for treatment to begin, the best dose, and the duration of use. “Prevention for ovarian and endometrial cancers remains elusive, but is not a lost cause,” they wrote.
Reference: Zeleznik OA, Irvin SR, Samimi G, Trabert B. The Role of Statins in the Prevention of Ovarian and Endometrial Cancers. Cancer Prev Res (Phila). 2023 Apr 3;16(4):191-197.
A Meta-Analysis of Metformin and Female Breast Cancer Risk
In the second publication, researchers reported findings from two separate meta-analyses: one estimating the relative risk of breast cancer in women with type 2 diabetes, and the other evaluating the risk of breast cancer in women with type 2 diabetes associated with metformin use. Approximately 40% of adults with type 2 diabetes take metformin as a treatment in the U.S.
Overall, the researchers looked at 45 studies, 30 in the meta-analysis of diabetes’ impact on breast cancer development and 15 in the review of whether women taking metformin had a lower risk of developing this cancer. The meta-analysis appeared in the journal Cancer Medicine.
In comparison to prior studies, the researchers wrote, their meta-analysis focused solely on type 2 diabetes to ensure results were not complicated by the differing disease types. Type 1 diabetes is caused by the destruction of cells that produce the hormone insulin in the pancreas. Researchers believe that the destruction is an autoimmune response triggered by genes or environmental exposures, such as viruses. Type 2 diabetes is when the body no longer uses insulin well, a problem known as insulin resistance. People with type 2 diabetes show inflammation in their bodies and have high insulin levels in their blood, which is known to increase the risk of developing cancers.
More than 15 million women in the U.S. have type 2 diabetes, which is recognized as an independent risk factor for developing breast cancer. The disease also raises the risk for other diseases, including cardiovascular and kidney diseases.
The researchers found that women with type 2 diabetes were about 15% more likely to be diagnosed with breast cancer than women without the disease. That association strengthened further, they wrote, when adjusted for body mass index (BMI) scores and menopausal status. Women taking metformin for their type 2 diabetes, however, had no statistically significant reduction in breast cancer risk in these observational studies. A recent clinical trial had similar results.
Future research will focus on understanding how conditions like diabetes could impact how often a women should be screened for breast cancer.
Reference: Lu Y, Hajjar A, Cryns VL, Trentham-Dietz A, Gangnon RE, Heckman-Stoddard BM, Alagoz O. Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis. Cancer Med. 2023 May;12(10):11703-11718. (Epub 2022 Dec 19).
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