STATINS AND BREAST CANCER INCIDENCE
Given the promising results detailed earlier, an important next step would be to evaluate the role of statins in breast cancer prevention. Another crucial consideration is whether or not statins have carcinogenic properties after long-term use.
Since randomized statin trials did not include breast cancer incidence as a primary endpoint, meta-analyses have been conducted to examine this relationship and they have reported no association between statin use and breast cancer risk. Studies by Bonovas et al23 and Undela et al24 examined breast cancer in particular, while others investigated cancers in general, including breast cancer25–28(refer Table 3 for an overview of these meta-analyses). When the relationship between statins and breast cancer risk was examined as part of the Women’s Health Initiative, a large US prevention study that enrolled >160,000 postmenopausal women aged 50–79 years over a period of 15 years; however, use of lipophilic statins was independently associated with a reduction in late-stage breast cancer diagnoses, specifically for those with estrogen receptor (ER)-positive cancers.29
When the incidence of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) was examined retrospectively in association with statin use, however, McDougall et al found that women taking statins for ≥10 years had an increased risk of invasive breast disease compared to patients who had never used statins. Furthermore, stratifying by ER status, the authors found twofold increases in risk for both ER+ IDC and ILC in the statin cohort. It is unclear, though, if a prolonged history of high cholesterol is the actual culprit, as the risk of developing breast cancer was stronger for patients with higher cholesterol levels.30
Arun et al conducted a prospective short-term prevention study to evaluate the effect of atorvastatin on biomarkers in the breast tissue and serum of women at an increased risk of breast cancer, ie, those with a previous history of carcinoma in situ or atypical hyperplasia, or an increased projected breast cancer risk given by accepted models. After 3 months, patients who were randomized to take atorvastatin had significantly decreased levels of serum C-reactive protein, cholesterol, and low-density lipoprotein. Atorvastatin metabolites were found in breast biopsies. Other tested tissue biomarkers – Ki-67, bcl-2, EGFR, and pEGFR – were not significantly different between the two groups.31 Thus, atorvastatin may help reduce inflammation and does accumulate in breast tissue.
Various breast cancer in vitro and animal studies have attempted to elucidate the mechanism by which statins exert their antitumor effects. In particular, the effect of statins on breast cancer invasion, migration, proliferation, apoptosis, and radiosensitivity has been studied in detail.
Preclinical data often direct clinical research, and thus, it is important to remain up to date regarding recent laboratory findings and their potential implications in the clinical arena. In particular, evidence suggests a potential role for statins in the neoadjuvant setting and/or in combination with other agents.