Triple-negative breast cancer (TNBC) is one of the most complex and challenging subtypes of breast cancer. Unlike other types, TNBC does not express hormone receptors or the HER2 receptor, which significantly limits targeted treatment options. This translates into a more aggressive disease, with a higher risk of recurrence and a lower survival rate. Faced with this scenario, scientific research has intensified the search for new therapeutic strategies that not only directly attack tumor cells but also modulate the molecular mechanisms that favor their growth, resistance, and dissemination. In this context, quercetin, a natural compound present in numerous plant-based foods, has generated growing interest as a potential complementary therapeutic agent.

Quercetin is a flavonoid, a type of bioactive compound that plants produce as a defense mechanism against environmental stress. In the human diet, it is naturally found in foods such as apples, onions, grapes, berries, broccoli, capers, and green tea, among others. For years, it has been recognized for its antioxidant and anti-inflammatory properties, meaning its ability to neutralize free radicals and reduce inflammatory processes. However, more recent research has shown that its potential goes far beyond this, especially in the context of cancer.

Several experimental studies have demonstrated that quercetin can interfere with multiple key biological processes involved in tumor development. Unlike many conventional treatments that act on a single molecular target, quercetin exhibits a multitarget action, meaning it can simultaneously influence several cellular signaling pathways altered in TNBC. This characteristic is particularly relevant in a tumor as heterogeneous as triple-negative breast cancer, where cancer cells use multiple mechanisms to survive and adapt.

One of the main antitumor effects of quercetin is the induction of apoptosis, a process known as programmed cell death. Under normal conditions, apoptosis allows the elimination of damaged or aged cells; however, in cancer, this mechanism is often blocked. Quercetin helps reactivate this pathway, promoting the selective elimination of tumor cells. In parallel, it also interferes with the cell cycle, the set of stages through which a cell divides, thereby reducing the uncontrolled proliferation characteristic of cancer.

At the molecular level, quercetin has the ability to modulate fundamental signaling pathways that are often overactivated in TNBC. One of the most important is the PI3K/Akt/mTOR pathway, which regulates essential functions such as cell survival, metabolism, and resistance to treatment. When this pathway is hyperactivated, tumor cells can survive even aggressive therapies. Quercetin has been shown to inhibit key components of this pathway, reducing signals that favor tumor survival and increasing the sensitivity of cancer cells to other treatments.

Another relevant pathway modulated by quercetin is JAK/STAT, a signaling system that allows cells to respond to cytokines and immune system factors. In the context of TNBC, this pathway can contribute both to tumor growth and to the creation of an unfavorable immune microenvironment. By modulating JAK/STAT, quercetin not only limits cell proliferation but could also promote a more effective antitumor immune response. Similarly, its effect has been observed on the Wnt/β-catenin pathway, which is involved in the self-renewal of tumor stem cells and in the ability of cancer to invade and metastasize.

The role of quercetin in metastasis, that is, the spread of cancer to other organs, is another highlighted aspect. TNBC has a high propensity to metastasize, a process that requires tumor cells to migrate and invade neighboring tissues. Quercetin reduces the expression of enzymes such as metalloproteinases, which degrade the extracellular matrix and facilitate tumor invasion. In addition, it can interfere with the epithelial–mesenchymal transition, a process through which cancer cells acquire greater mobility and aggressiveness.

A particularly relevant point is quercetin’s ability to enhance the efficacy of conventional treatments. Studies show that this compound can increase the sensitivity of TNBC to chemotherapy, helping to overcome resistance mechanisms that often appear during treatment. At the same time, its low-toxicity profile suggests that it could help reduce side effects, which is especially important for patients’ quality of life.

Figure 1. Quercetin, a naturally occurring plant-derived compound, is associated with the regulation of multiple cellular and immune processes involved in tumor development, cancer cell survival, immune modulation, and disease progression.

Nevertheless, the clinical use of quercetin faces significant challenges, the main one being its low bioavailability, that is, the difficulty for the compound to reach effective concentrations in the body when consumed in a traditional manner. To address this limitation, current research is focused on the development of nanoparticles and controlled-release systems, technologies that allow the compound to be protected, improve its absorption, and deliver it more efficiently to the tumor.

Overall, the evidence positions quercetin as a promising natural compound in the management of triple-negative breast cancer, not as a substitute for current therapies, but as a complement capable of acting on multiple mechanisms of the disease. Its ability to modulate key signaling pathways, influence the tumor microenvironment, and enhance the response to existing treatments reinforces its potential within modern approaches to integrative and precision oncology. Although additional clinical studies are still required, current advances suggest that compounds present in the everyday diet could play a relevant role in the future of personalized cancer treatment.

Main reference:

Wu, Z. Y., Qiu, K. Y., Gai, Y. J., Wu, J. H., Zhou, B. X., & Shi, Q. F. (2025). Quercetin: A Natural Ally in Combating Breast Cancer. International journal of nanomedicine, 20, 9155–9177. https://doi.org/10.2147/IJN.S518174

Other references:

Weber, W. P., Hanson, S. E., Wong, D. E., Heidinger, M., Montagna, G., Cafferty, F. H., Kirby, A. M., & Coles, C. E. (2024). Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 44(3), e438776. https://doi.org/10.1200/EDBK_438776

Nolan, E., Lindeman, G. J., & Visvader, J. E. (2023). Deciphering breast cancer: from biology to the clinic. Cell, 186(8), 1708–1728. https://doi.org/10.1016/j.cell.2023.01.040

Borri, F., & Granaglia, A. (2021). Pathology of triple negative breast cancer. Seminars in cancer biology, 72, 136–145. https://doi.org/10.1016/j.semcancer.2020.06.005