Endometrial Cancer and The Role of Statins

Dear Editor, According to the new guidelines published by the American College of Cardiology, it is predicted by experts that statins will become one of the most commonly prescribed drugs in the age group of 40-75 years.[1] Statins have been clearly shown to improve morbidity and mortality in patients with cardiovascular diseases. Recently, the beneficial effect of statins on the prognosis and risk of various cancers including gynecological malignancies has also been highlighted in multiple studies. Endometrial cancer, the most common cancer of the female genital tract, has already caused more than 10,000 mortalities in the United States alone in the year 2015.[2] With advanced-stage endometrial cancer presenting with an extremely poor outcome, it is important that factors that can help to decrease the risk of endometrial cancer should be thoroughly investigated. The role of statins in this regard has been highly debatable in the recent past. In an attempt to collect updated evidence, we conducted an extensive literature search utilizing Medline (PubMed and OvidSP) and Cochrane Library to identify all possible studies that have investigated the impact of statins on the risk and prognosis of endometrial cancer. Thirteen relevant citations were found[3,4,5,6,7,8,9,10,11,12,13,14,15] and are shown in Tables ​Tables11 and ​and2.2. Three studies[5,6,7] showed that statins significantly reduce the risk of developing endometrial cancer while seven studies[8,9,10,11,12,13,14] reported no such relationship. The three studies that documented favorable impact of statins on endometrial cancers were all limited by lack of randomization, single center locations, relatively small sample sizes, and confounders as patients had multiple comorbidities. Only three studies[3,4,12] were found that investigated the effect of statins on endometrial cancer survival, which are shown in Table 2. Nevadunsky et al.[3] reported that statins significantly (HR = 0.63) prolong survival in patients with endometrial cancer while the other two studies[4,12] concluded that statins have no significant effect on mortality. These studies have not mentioned if they have looked at progression-free survival or overall survival versus a cancer specific outcome such as time to recurrence. Table 1 Summary of the evidence regarding role of statins in the risk of endometrial cancer Table 2 Summary of evidence regarding statins and outcome of endometrial cancer It is vital to consider the duration of statin usage as well. In a recent meta-analysis by Liu et al.,[15] it was shown that when statins were taken for greater than 5 years, the risk of endometrial cancer was reduced by 31%. Moreover, they reported that studies conducted in Asian populations only had a significant relationship when all potential confounders were considered. It is important to note that patients who take statins tend to be elderly, have multiple comorbidities, and medication regimens including use of hormonal therapy; hence it is imperative to take these confounders into account. These conflicting outcomes warrant further clinical investigation on the role of statins in endometrial cancer. We suggest that histological differentiation of endometrial cancer must also be analyzed in the future studies as different subtypes of endometrial cancer are closely linked with the prognosis. Moreover, randomized clinical trials are needed in this field urgently to eliminate selection, recall, and confounding bias inherent to observational studies. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.