Atorvastatin is one of the most widely used medications for lowering cholesterol and preventing cardiovascular complications. Its main function is to block an enzyme called HMG-CoA reductase, a central component of the pathway through which cells produce cholesterol and other molecules necessary for growth and normal function.
However, this same metabolic pathway also participates in processes that are relevant to cancer, such as cell proliferation, inflammation, and protein communication. For this reason, researchers have been asking for several years whether drugs that interfere with this pathway, known as statins, might also have additional effects on tumor development or progression.
A study published in Scientific Reports explored this possibility by analyzing large gene-expression datasets. Its results suggest that atorvastatin, in particular, may modify a molecular signature associated with early changes in breast tissue. Nevertheless, this is preliminary and computational evidence, meaning that the study does not prove that taking atorvastatin prevents breast cancer or that it should be used as an anticancer treatment.
Tissue near a tumor is not always completely normal
When a tumor is analyzed in a biopsy, it is usually compared with apparently healthy tissue from another location. However, there is an especially interesting intermediate category: tissue adjacent to the tumor.
To the naked eye and under the microscope, this tissue may appear normal. Even so, its cells may already show changes in the activity of certain genes, in inflammatory responses, or in communication with the immune system. In other words, although it is not yet tumor tissue, it may be influenced by the nearby cancer or share some early alterations that favor malignant transformation.
The researchers analyzed two databases comparing normal breast tissue, obtained mainly from breast reduction surgeries, with non-tumor tissue located near breast cancers. The analysis revealed 116 genes that were expressed differently between the two tissue types.
What does atorvastatin have to do with this?
To study the potential effect of the drug, the authors used another dataset that included patient samples collected before and after atorvastatin treatment. Because the samples came from the same individuals, the design made it possible to observe which genes changed after treatment while partially reducing the influence of individual differences.
The treatment lasted approximately two weeks. When the researchers analyzed the samples globally, they did not observe a marked separation between the profiles before and after the medication. This suggests that atorvastatin did not produce a massive reprogramming of the cells during that period.
Even so, a more specific analysis identified 105 genes whose expression changed after treatment. In other words, the overall effect appeared modest, but certain specific molecular programs did show detectable changes.
The scientists then compared two lists:
- genes altered in breast tissue near the tumor;
- genes modified after atorvastatin treatment.
They found 13 genes in common. However, the most striking finding was that these genes showed opposite patterns. In other words, when they were altered in tumor-adjacent tissue, atorvastatin tended to modify their expression in the opposite direction. The authors interpreted this result as a possible reversal of an early tumorigenic signature.
What does it mean to “reverse a gene signature”?
A gene signature is a group of genes whose activity forms a recognizable pattern. It can be imagined as a molecular fingerprint: it does not depend on a single gene, but on the coordinated behavior of several genes.
When a disease causes certain genes to increase or decrease their activity, a drug capable of shifting them in the opposite direction could, in theory, counteract part of the biological process associated with the disease.
It is possible that these molecular changes are indirect, temporary, or insufficient to produce a clinical benefit. Reversal of a signature is therefore an interesting signal for further investigation, but not proof of therapeutic effectiveness.
In this study, the overlap among the 13 genes did not appear to be due to chance according to the statistical analysis. In addition, the proteins produced by these genes are part of an interconnected network of biological processes.
Figure 1. Changes in gene expression associated with tumor-adjacent breast tissue and short-term atorvastatin treatment, highlighting a shared molecular signature linked to proliferation, inflammation, cell death, and cellular stress.
Inflammation, cellular stress, and growth control
The detected gene signature was associated with processes such as antitumor responses, inflammation, cellular adaptation to adverse conditions, DNA repair, and programmed cell death.
These processes are deeply connected to cancer biology. For example, persistent inflammation can promote cell proliferation and modify the tissue surrounding a tumor. Low-oxygen conditions can select tumor cells that are more adaptable and aggressive. Programmed cell death, in turn, helps stop the division of severely damaged cells or promotes their elimination.
One plausible explanation is that by inhibiting HMG-CoA reductase, atorvastatin reduces cholesterol production, but it also decreases the production of other compounds derived from the same pathway.
Tumor cells need to produce new membranes in order to divide, and they may depend heavily on metabolic pathways that provide cholesterol and lipids. Interfering with this pathway could therefore affect their ability to grow.
Atorvastatin also does not act exclusively on tumor cells. It may affect hepatocytes, immune cells, adipose tissue, and other components of the body. This broad range of effects explains both its potential and the difficulty of predicting its impact in oncology.
A possible change in the immune microenvironment
Cancer is not made up only of malignant cells. Around the tumor are immune cells, fibroblasts, blood vessels, and structural components that together form the tumor microenvironment. The authors used a computational method to estimate which immune populations were present in the samples. In tissue adjacent to the tumor, they observed a greater representation of regulatory T cells and a lower presence of monocytes.
After atorvastatin treatment, a decrease in regulatory T cells and an increase in monocytes were observed. A greater presence of activated CD4 memory T cells was also reported. This suggests that the drug could influence the immune balance of the tissue, potentially favoring immune stimulation. Although these populations were inferred computationally, the findings may still indicate a possible immunological effect.
The researchers then analyzed the 13-gene signature in larger breast cancer databases. Alteration of these genes was associated with features linked to more aggressive tumors and with a higher risk of death or recurrence. This raises the possibility that the signature may have prognostic value and that restoring its expression could be beneficial.
However, these results must be interpreted with caution…
What the study still does not demonstrate
The work was based mainly on the reuse and combination of public datasets. It was not a clinical trial designed to determine whether atorvastatin prevents breast cancer. It also did not compare cancer incidence over several years between people who received the drug and those who did not.
Functional experiments are needed to determine whether modifying the 13 genes actually reduces malignant transformation. Prospective clinical trials would also be required to establish which patients might benefit, what dose would be appropriate, and how long treatment should continue.
Based on the current evidence, atorvastatin should be used according to established medical indications, mainly to control cholesterol and reduce cardiovascular risk. A person should not start, stop, or modify treatment with the intention of preventing cancer without consulting a physician.
Even so, the study presents an important idea: some medications developed for non-oncological diseases may be able to modify biological processes that are relevant to cancer.
Atorvastatin is particularly interesting because it has decades of clinical use, well-studied pharmacology, and a known safety profile. This could make future trials easier to conduct if additional research confirms its usefulness in specific patient groups.
The main conclusion is not that atorvastatin is currently a preventive treatment for breast cancer. Rather, understanding its biological effects could help identify new preventive strategies and select patients in whom targeting this pathway may be meaningful.
Main reference:
Foda, M. Y., Salem, M. L., AlAkwaa, F. M., & El-Khawaga, O. Y. (2024). Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature. Scientific reports, 14(1), 17803. https://doi.org/10.1038/s41598-024-67706-2
Other references:
Bashey, S. Z., Kordon, A., Ositelu, K., Rao, A., & Akhter, N. (2025). The role of statins in breast cancer survivors. Breast cancer research and treatment, 210(1), 1–10. https://doi.org/10.1007/s10549-024-07605-2
Kandasamy, T., Sarkar, S., & Ghosh, S. S. (2024). Harnessing Drug Repurposing to Combat Breast Cancer by Targeting Altered Metabolism and Epithelial-to-Mesenchymal Transition Pathways. ACS pharmacology & translational science, 7(12), 3780–3794. https://doi.org/10.1021/acsptsci.4c00545
