on October 06, 2026
Endocrine therapy has transformed the natural history of estrogen receptor-positive and/or progesterone receptor-positive breast cancer. Tamoxifen and aromatase inhibitors are, in fact, essential tools for reducing the risk of recurrence in patients whose tumors depend, to varying degrees, on hormonal stimulation.
But an effective therapy is not necessarily free of consequences.
The reduction of estrogenic activity can be accompanied by arthralgia and joint stiffness, changes in body composition, increased fat mass, metabolic alterations, loss of bone mass, and menopausal symptoms. These issues can profoundly affect quality of life and, in some patients, make it more difficult to maintain the prescribed therapy over time.
This gives rise to the interest in personalized oncological nutrition: not as an alternative to anticancer therapy, but as a possible component of an integrated approach aimed at preserving muscle and bone mass, metabolic control, cardiovascular health, functionality, and quality of life.
A literature review published in 2025 specifically analyzed diet, foods, and supplements in women with breast cancer undergoing endocrine therapy, identifying 26 studies considered relevant out of over a thousand initially identified records. The most studied areas included body composition, bone health, cardiovascular risk, inflammation, and quality of life. The authors found interventions based on the Mediterranean diet and certain nutrients to be promising, but they highlighted the considerable heterogeneity of the studies and the need for further clinical trials.
Endocrine therapy and quality of life: the problem of treatment continuity
The side effects of endocrine therapy are not merely a symptomatic issue.
Joint pain, stiffness, fatigue, sleep disorders, and menopausal symptoms can interfere with daily life and become one of the reasons why some patients discontinue or irregularly take the therapy.
Aromatase inhibitors, in particular, drastically reduce the peripheral production of estrogens in postmenopausal women. This condition is favorable from an anticancer standpoint in hormone-sensitive tumors, but it can have consequences on the musculoskeletal system and bone metabolism.
Quality of life therefore becomes an integral part of the oncological journey.
A systematic review of longitudinal studies on adjuvant endocrine therapy highlighted that treatment-related issues can persist over time, making multidisciplinary management of adverse effects important.
The goal of nutrition is therefore not to "neutralize" the action of the drug, but to create metabolic and nutritional conditions that allow the patient to better cope with the long therapeutic journey.
The Mediterranean diet as a reference nutritional model
Among the dietary models studied in patients with breast cancer, the Mediterranean diet holds a special place.
The model is not identified with a single food or supplement, but with an overall structure characterized by:
- high consumption of fruits and vegetables;
- legumes;
- predominantly whole grains;
- extra virgin olive oil as the main source of fat;
- nuts and seeds;
- regular consumption of fish;
- limitation of processed meats, ultra-processed foods, and saturated fats;
- adequate fiber intake;
- moderate consumption of foods of animal origin.
The biological rationale includes the modulation of energy metabolism, inflammation, oxidative stress, the intestinal microbiota, and body composition.
A systematic review and meta-analysis dedicated to the Mediterranean diet in breast cancer survivors included 11 studies. In observational cohorts, greater adherence to the Mediterranean diet was associated with lower all-cause mortality and lower mortality not attributable to breast cancer, although the certainty of the evidence was judged to be low or very low. The effects on quality of life, however, were less uniform.
This point is fundamental: an epidemiological association does not prove that the Mediterranean diet alone reduces cancer mortality. However, its nutritional profile is consistent with numerous cardiovascular and metabolic prevention goals that are particularly relevant in the long term.
Diet, body weight, and adipose tissue
Estrogen deprivation can contribute to changes in body composition, especially in menopausal women.
The increase in fat mass is not merely an aesthetic change. Adipose tissue is a true endocrine organ capable of producing adipokines, inflammatory mediators, and, through peripheral aromatase, contributing to estrogen production.
Obesity, insulin resistance, and chronic inflammation also constitute an unfavorable metabolic environment for cardiovascular and general health.
A randomized study in women with breast cancer evaluated a personalized intervention based on the Mediterranean diet combined with physical activity recommendations. After three months, the intervention group showed greater adherence to the Mediterranean diet, a reduction in body weight and fat mass, and an improvement in quality of life.
A pilot trial conducted in overweight or obese breast cancer survivors also observed, after eight weeks on the Mediterranean diet, a reduction in weight, blood glucose, and insulin levels, with an improvement in quality of life; however, the additional effect of an anti-obesity drug compared to the Mediterranean diet alone was not found to be significant.
Weight management must therefore be considered part of the overall survivorship strategy, while avoiding turning calorie restriction into a state of malnutrition.
Omega-3: a possible support, but not a universal solution for arthralgia
EPA and DHA are long-chain polyunsaturated fatty acids belonging to the omega-3 family.
Their interest in nutritional oncology derives mainly from their ability to modulate the composition of cell membranes and the production of lipid inflammatory mediators.
EPA and DHA give rise to specialized mediators of inflammation resolution, including resolvins, protectins, and maresins.
This rationale led to the study of omega-3s in patients treated with aromatase inhibitors, in whom arthralgia is one of the most common side effects.
The results, however, are far from uniform.
In the large SWOG S0927 trial, 249 women with breast cancer receiving aromatase inhibitor therapy and significant joint pain were randomized to receive 3.3 g/day of omega-3s or placebo for 24 weeks. Pain improved in both groups, but no significant difference emerged between omega-3s and placebo in the primary analysis. Triglycerides, on the other hand, decreased significantly in the omega-3 group.
An exploratory analysis of the same study provided an interesting finding: in obese women, omega-3s were associated with a greater reduction in pain compared to placebo, while this difference did not emerge in non-obese women.
Another small randomized trial showed that high-dose supplementation was feasible and well tolerated, with a possible favorable effect on quality of life, but without a statistically significant reduction in pain severity.
Overall meta-analyses therefore suggest a possible benefit on certain inflammatory, metabolic, and quality-of-life parameters, but do not allow for a recommendation of omega-3s as a universal treatment for aromatase inhibitor-induced arthralgia.
Vitamin D: bones, muscles, and a possible role in joint symptoms
Skeletal health deserves particular attention during aromatase inhibitor therapy.
Estrogen reduction accelerates bone turnover and can promote loss of mineral density and an increased risk of fracture.
Vitamin D contributes to calcium and phosphorus homeostasis and musculoskeletal physiology. For this reason, it is important to check and correct any deficiency, while avoiding interpreting vitamin D as an anticancer therapy.
Studies on the effects of supplementation on musculoskeletal disorders have produced conflicting results.
In a phase II randomized trial, 60 women with breast cancer receiving anastrozole therapy and musculoskeletal symptoms received high-dose vitamin D2 or placebo. The treated group showed improvements in several pain indicators and a possible favorable effect on femoral neck bone density.
Conversely, the VITAL trial, conducted in 160 women starting letrozole, did not reach its primary endpoint related to the prevention of musculoskeletal symptoms, although an analysis based on a different pain assessment tool suggested a possible benefit.
The most cautious conclusion is therefore that correcting vitamin D deficiency is important for bone health, while its specific effect on aromatase inhibitor-induced arthralgia remains uncertain.
Bone health: nutrition and pharmacological treatment must proceed together
Skeletal protection cannot be entrusted exclusively to supplements.
Adequate dietary calcium, vitamin D when indicated, physical activity with strength and resistance exercises, adequate protein intake, and control of risk factors constitute a set of complementary interventions.
When there is a high risk of osteoporosis, the doctor can also evaluate specific anti-resorptive drugs.
A randomized trial conducted in postmenopausal women with hormone receptor-positive breast cancer and low bone mass demonstrated that risedronate, combined with calcium and vitamin D, could preserve skeletal health during aromatase inhibitor therapy.
This example shows a general principle of oncological nutrition: diet and micronutrients can support physiology, but they must not be confused with the pharmacological interventions necessary when clinical risk requires them.
Coenzyme Q10: mitochondrial energy and inflammation
Coenzyme Q10 is an essential component of the mitochondrial respiratory chain and participates in ATP production.
Its function in electron transfer and its ability to participate in antioxidant systems have also generated interest in the oncological context.
A randomized, double-blind, placebo-controlled study evaluated 100 mg/day of CoQ10 for two months in women with breast cancer undergoing tamoxifen. Supplementation resulted in a significant reduction in serum concentrations of IL-6 and IL-8 compared to placebo, while no significant difference emerged for VEGF.
A previous study had used a combination of CoQ10, riboflavin, and niacin in women treated with tamoxifen, observing a reduction in several cytokine mediators.
A meta-analysis of randomized trials subsequently suggested favorable effects of CoQ10 on certain inflammatory and molecular biomarkers, but also highlighted considerable heterogeneity among the studies.
These results are biologically interesting, but they do not prove that CoQ10 improves survival or the anticancer efficacy of tamoxifen.
Inflammation and metabolic microenvironment
Breast cancer and its treatments can be accompanied by changes in the metabolic and inflammatory environment.
C-reactive protein, IL-6, TNF-α and other mediators have been studied as possible indicators of systemic inflammation.
From a nutritional perspective, the most rational strategy is not to pursue a single biomarker, but to reduce the conditions that chronically fuel inflammation: excess adiposity, sedentary behavior, a low-fiber diet, high consumption of ultra-processed foods, metabolic alterations, and insufficient physical activity.
This is one of the reasons why the Mediterranean model appears more compelling than a single substance.
A recent systematic review on the Mediterranean diet in women with breast cancer has indeed highlighted the possible combined role of unsaturated fats, polyphenols, carotenoids, and plant-based foods in supporting metabolic parameters and quality of life, while emphasizing the need for more robust clinical studies.
Red clover: biological interest and the need for caution
Red clover contains isoflavones, including formononetin and biochanin A, compounds capable of interacting with estrogen receptors.
This makes its use in women with hormone-sensitive breast cancer a particularly delicate topic.
A randomized trial in premenopausal women with ER-positive breast cancer treated with tamoxifen compared 80 mg/day of red clover extract with placebo for 24 months, within the context of a general recommendation to follow a Mediterranean-style diet and maintain an active lifestyle.
The menopausal symptom score improved in both groups without a significant difference between them. However, greater reductions in BMI and waist circumference were observed in the group treated with red clover.
The result does not demonstrate an antitumor efficacy of red clover.
Furthermore, precisely because it is a source of phytoestrogenic compounds in patients with hormone-sensitive tumors, the possible use of concentrated extracts must be agreed upon with the oncologist, taking into account the type of tumor, the endocrine therapy, and possible interactions.
Whole grains, fiber, and metabolism
Whole grains represent one of the most interesting components of a dietary strategy aimed at metabolic health.
The presence of fiber, vitamins, minerals, and numerous phytochemical substances helps differentiate whole grains from refined products.
Fiber also influences the gut microbiota, postprandial glycemic response, satiety, and bile acid metabolism.
Some phytochemical compounds in whole grains, including lignans, phenolic acids, phytosterols, and tocopherols, possess antioxidant activities and can modulate various cellular pathways.
However, the possibility of attributing a clinically significant antitumor action to a specific component of whole grains in patients undergoing endocrine therapy is not yet demonstrated.
Their value derives mainly from the fact that they are part of an overall dietary pattern favorable to metabolic control.
Fasting and fast-mimicking diet: a still-experimental frontier
Among the most innovative nutritional strategies in breast cancer is the fast-mimicking diet.
The biological rationale stems from the observation that a temporary reduction in energy intake can alter insulin, IGF-1, leptin, and other metabolic pathways involved in cell growth.
An important experimental study showed, in mouse models of hormone receptor-positive breast cancer, that periodic fasting and the fast-mimicking diet could increase the activity of tamoxifen and fulvestrant. The mechanism was associated with the reduction of IGF-1, insulin, and leptin, and the modulation of the AKT-mTOR pathway.
The same work also included preliminary clinical data in patients, showing metabolic changes consistent with those observed in experimental models.
But the most important part is what this study does not demonstrate: it does not demonstrate that a fast-mimicking diet is already a standard oncological therapy.
Subsequent research has further explored the possible role of glucocorticoids and the glucocorticoid receptor in enhancing the anti-estrogenic activity of fasting, providing new biological bases for clinical studies.
The field is therefore extremely interesting, but still experimental.
Significant calorie restriction may also be inappropriate in patients with weight loss, sarcopenia, malnutrition, or increased nutritional requirements.
Diet must not become a second therapy to endure
This is a central point of oncological nutrition.
A patient undergoing endocrine therapy may already be engaged in a long and complex journey. The introduction of extremely restrictive diets, indiscriminate food eliminations, prolonged fasts, or numerous supplements can turn into an additional physical and psychological burden.
The goal should be exactly the opposite: to make nutrition sustainable, pleasant, nutritionally adequate, and compatible with daily life.
A recent umbrella review of reviews on nutrition in breast cancer survivors highlighted relatively consistent benefits of structured nutritional interventions on diet quality, weight, adiposity, and several domains of quality of life. The most promising interventions are those that are structured and accompanied by adequate nutritional support.
Physical activity and nutrition: a biologically coherent combination
Nutrition should not be considered in isolation.
Physical activity contributes to the control of body fat, the preservation of muscle mass, bone and cardiovascular health, and psychological well-being.
Resistance exercise, in particular, represents an important stimulus for the maintenance of muscle mass and strength, while weight-bearing exercise contributes to skeletal health.
The combination of a balanced diet and movement therefore appears more consistent with physiology than the search for a single "anti-cancer" molecule.
A randomized study on patients with breast cancer showed that a lifestyle intervention including the Mediterranean diet and physical activity was associated with improvements in quality of life, fatigue, and several functional domains.
From biomolecular nutrition to personalization
The concept of a biomolecular diet can be interpreted in a scientifically useful way if it is not understood as a standardized diet or as an alternative therapy to oncological treatment.
It means rather considering the relationship between foods, nutrients, and biological systems:
fiber → microbiota and intestinal metabolism
omega-3 → lipid mediators and resolution of inflammation
vitamin D → bone metabolism and musculoskeletal function
polyphenols → redox pathways and cellular signaling
proteins → muscle mass and functional recovery
unsaturated fats → cardiovascular metabolism
dietary energy → insulin, leptin, and systemic metabolism
This perspective allows for a transition from generic nutrition to nutrition that is more tailored to the individual patient's condition.
A woman with obesity and dyslipidemia will have different needs compared to a normoweight patient with muscle mass loss. A woman with osteopenia will require different attention compared to a patient without bone risk factors. A patient with a significant vitamin D deficiency will have different needs from someone with adequate levels.
Personalization is therefore more important than a simple list of supplements.
What we really know today
The available evidence allows us to outline a fairly clear hierarchy.
The Mediterranean diet has a solid biological rationale and favorable observational and interventional evidence, especially for body composition, diet quality, metabolic health, and quality of life, while the effects on survival require more robust prospective studies.
Omega-3s can improve some lipid and inflammatory parameters and could play a role in specific subgroups, but they have not demonstrated a uniform benefit on aromatase inhibitor-induced arthralgia.
Vitamin D is important especially when there is insufficiency or risk of bone loss; the effects on joint symptoms are less consistent across studies.
Coenzyme Q10 shows interesting results on inflammatory biomarkers, but there is insufficient evidence to attribute an antitumor effect or effect on survival to it.
Red clover shows preliminary results on some metabolic and menopausal parameters, but the presence of phytoestrogens requires particular caution in patients with hormone-sensitive breast cancer.
The fast-mimicking diet is one of the most interesting frontiers of metabolic research on breast cancer, but the clinical evidence is not yet sufficient to consider it a therapeutic standard.
An integrated strategy to support endocrine therapy
The most promising perspective is not to replace endocrine therapy with a diet or a supplement, but to build a favorable nutritional and behavioral environment around pharmacological therapy.
A rational strategy can include:
predominantly Mediterranean diet, rich in plant-based foods, legumes, whole grains, fish, extra virgin olive oil, nuts, and fiber;
body composition control, avoiding both excess adiposity and involuntary weight and muscle mass loss;
adequate protein intake, personalized according to age, physical activity, renal function, and body composition;
attention to bone health, through adequate levels of calcium and vitamin D, resistance exercise, and osteoporosis risk assessment;
regular physical activity, including aerobic exercise, strength training, and, when appropriate, weight-bearing activity;
individual assessment of supplements, based on documented deficiencies, clinical goals, and possible drug interactions;
metabolic monitoring, especially regarding weight, blood glucose, lipid profile, blood pressure, and vitamin status;
quality of life support, because reducing pain, fatigue, and metabolic disorders also makes a treatment that can last for many years more sustainable.
Nutrition as part of care, not as an alternative to care
Hormone receptor-positive breast cancer requires a rigorous and personalized therapeutic strategy.
Nutrition can, however, become an important supportive element.
Contemporary research is gradually shifting the focus from the simple question "Which food fights cancer?" toward a biologically more correct question: how can we use nutrition, physical activity, and the correction of nutritional deficiencies to keep the body in the best possible metabolic condition during and after oncological treatment?
It is a substantial difference.
This does not mean promising that a diet can cure breast cancer. It means recognizing that metabolism, inflammation, body composition, cardiovascular health, bone tissue, and quality of life are real components of the health of oncology patients.
In this perspective, the Mediterranean diet represents today the model with the most solid overall rationale, while omega-3, vitamin D, coenzyme Q10, and other bioactive substances constitute tools of interest to be evaluated case by case.
The future of oncology nutrition could therefore be increasingly personalized: not the same diet for all patients, but a path built on individual biology, the type of cancer, the therapy received, body composition, metabolism, and side effects.
A true precision medicine, in which nutrition does not replace medication, but contributes to modulating the physiological terrain on which the therapy acts.
Essential bibliographic references
- Current Evidence on the Impact of Diet, Food, and Supplement Intake on Breast Cancer Health Outcomes in Patients Undergoing Endocrine Therapy. 2025. Literature review specifically dedicated to diet, food, and supplements in patients with breast cancer undergoing endocrine therapy.
- The Role of the Mediterranean Diet in Breast Cancer Survivorship: A Systematic Review and Meta-Analysis of Observational Studies and Randomised Controlled Trials. 2023.
- The Impact of Dietary Unsaturated Fat or the Mediterranean Diet on Women Diagnosed With Breast Cancer: A Systematic Review. 2024.
- Application of Clinical Decision Support System to Assist Breast Cancer Patients with Lifestyle Modifications during the COVID-19 Pandemic: A Randomised Controlled Trial. Nutrients, 2021.
- Quality of Life in Women Diagnosed with Breast Cancer after a 12-Month Treatment of Lifestyle Modifications. 2021.
- Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927. Journal of Clinical Oncology, 2015.
- Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia. 2018.
- Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms: a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment, 2011.
- Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole: the VITAL trial. Breast Cancer Research and Treatment, 2017.
- The Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Growth Factor and Serum Levels of Interleukin 6 and 8 in Women with Breast Cancer: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. 2019.
- Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled trials. 2021.
- Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen. 2020.
- Fasting-mimicking diet and hormone therapy induce breast cancer regression. 2020. Preclinical study with preliminary human metabolic data.
- Fasting boosts breast cancer therapy efficacy via glucocorticoid activation. 2025. Study on the biological mechanisms and clinical data associated with the fasting-mimicking diet and endocrine therapy.
- Dietary and Nutrition Interventions for Breast Cancer Survivors: An Umbrella Review. 2026.
