Breast cancer is the most common cancer in women worldwide with an unfortunate steady increase in the number of women diagnosed with breast cancer. The concerning increase in breast cancer incidence is forcing action to be taken at all levels of prevention.
Comparable to the increased incidence of breast cancer, obesity is a pressing public health concern with rapidly rising rates during the last decades. The positive association between a more obese body constitution on risk of breast cancer has convincingly been demonstrated in several studies including our Malmö Diet and Cancer based studies. Obesity associated alterations in circulating lipids/cholesterol might partly link the association between obesity and breast cancer. However, the observed epidemiological linkage between obesity and breast cancer remains poorly understood biologically; both in terms of effects from the local micro-environmental on progression, and also regarding breast cancer initiation, an area that has hardly been explored.
Interestingly, cholesterol-lowering statins have received substantial attention in the field of cancer research lately, including chemoprevention. Epidemiological studies have indicated lower cancer incidence among statin users, although the results have been inconsistent across studies, including our latest update from the large-scaled Nurses Health Study showing neutral associations. Thus, we concluded that in future studies of statins in relation to breast cancer incidence, it may be best to explore effects in an appropriately powered primary prevention trial among high-risk women.
Subsequently, an emerging field of statin in vitro/in vivo studies and clinical trials investigating the effects of statins have been performed, and many more are under their way. So far, statins have been shown to decrease proliferation and increase apoptosis of breast cancer cells. However, no studies have investigated the effects in normal breast epithelial cells, which is of foremost importance to understand the potential role of statins in breast cancer initiation and thus prevention. Although the biological mechanisms for the actions in breast cancer are not fully elucidated, hydroxy-methyl-glutaryl coenzyme A reductase (HMGCR) is the well-recognized target of statins, exerting its cholesterol-lowering effects on hepatocytes, but statins probably also exert effects via direct effects on extra-hepatic cells.
Taken together, the incidence of both obesity and breast cancer are rising and can be targeted simultaneously. Cancer initiation, progression and survival depend on sustained intracellular lipid metabolism evidently influenced by circulating lipid levels, local cholesterol synthesis, and interactions with adipocytes in the local microenvironment of the breast. The systemic and local cholesterol synthesis is tightly regulated by the mevalonate pathway. HMGCR being the rate-limiting enzyme in the mevalonate pathway, is pharmacologically targeted by statins and the expression of HMGCR in breast cancer and probably even in normal breast cells suggest that statins can be a promising preventive and treatment active drug in breast cancer. Breast cancer preventive actions through changes in modifiable life style factors and medical intervention are currently not established in Sweden, although identified as a key area of improvement.