Cancer mortality rates are declining globally, yet metastasis and relapse after surgery and adjuvant treatments remain significant challenges. Recent advances in genomics, metabolomics, and proteomics enhance our understanding of cancer metabolic diversity, leading to detailed tumor classifications and more effective precision medicine. Simultaneously, growing knowledge of the interactions between nutrients and gene expression could lead to cancer therapies based on precision nutrition strategies.
The Foundation of a Cancer-Protective Diet
The healthiest eating pattern is primarily based on plant foods like vegetables, fruits, whole grains, beans, and nuts/seeds. It also includes healthy protein sources, such as fish or poultry, while limiting red and processed meats. Studies have consistently linked these dietary patterns to a lower risk of cancer, other diseases, and early death.
The Power of Plant-Based Foods
Vegetables and Fruits: These are packed with vitamins, minerals, fiber, and other substances that may help prevent cancer. Eating plenty of vegetables and fruits can also aid in weight management, as they are low in calories, high in fiber, and rich in water. Phytonutrients are also responsible for bright colors in fruits and vegetables. Tomatoes get their vibrant red hue from the phytonutrient lycopene, and the deep purple stains left on your fingers after eating blueberries are from a group of phytonutrients called anthocyanins.
Whole Grains: Whole grains retain all parts of the original grain, providing more fiber and nutrients compared to refined grains. Examples include whole wheat, brown or wild rice, oats, and corn. Studies suggest that eating whole grains might lower the risk of colorectal cancer.
Dietary Fiber: Found in plant foods like beans, whole grains, fruits, vegetables, nuts, and seeds, dietary fiber can help prevent excess body weight, which can lower cancer risk. However, studies on fiber supplements like psyllium fiber and wheat bran fiber haven’t shown a reduction in colon polyps.
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Limiting Unhealthy Foods
Processed Meats: Processed meat has been cured, smoked, salted, or fermented to improve or preserve flavor. Examples include bacon, sausage, hot dogs, and deli meats. Evidence that red and processed meats increase cancer risk has existed for decades, and many health organizations recommend limiting or avoiding these foods. In 2015, the International Agency for Research on Cancer (IARC) classified processed meat as “carcinogenic [cancer-causing] to humans” (Group 1) and red meat as “probably carcinogenic to humans” (Group 2A), based on evidence that they increase the risk for colorectal cancer. Because of this, it is recommended to eat more protein from fish, poultry, and beans instead of red meat.
Added Sugars and Ultra-Processed Foods: Added sugars and other high-calorie sweeteners are often used in sugar-sweetened beverages and energy-dense foods like traditional “fast food” or ultra-processed foods (UPFs). These highly processed foods are usually high in fat, sugar, refined grains, and salt. Studies have linked them to health problems, including weight gain, and more research is needed to understand their impact on cancer risk.
Other Dietary Considerations
Calcium and Dairy: Some research has linked diets high in calcium and dairy products to a lower risk of colorectal cancer, and possibly breast cancer as well. However, some studies have also suggested that calcium and dairy products might increase prostate cancer risk.
Vitamin D: Vitamin D, made by the body when the skin is exposed to ultraviolet (UV) rays, helps keep bones and the immune system healthy. You can also get it from foods like fatty fish, some mushrooms, fortified foods (milk, orange juices, cereals) or from supplements. Some studies suggest vitamin D might lower cancer risk, particularly colorectal cancer. While research continues on vitamin D and cancer risk, avoiding low vitamin D levels is recommended.
Dietary Supplements: While dietary supplements can provide some benefit, they also have risks and are not regulated the same way as medicines are. Eating a diet rich in vegetables, fruits, and other plant foods may lower cancer risk, but there’s little consistent evidence that dietary supplements do the same. Some high-dose supplements containing nutrients such as beta-carotene and vitamins A and E may actually increase the risk of some cancers. Food is the best source of vitamins, minerals, and other important food components.
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Precision Nutrition: Targeting Cancer Relapse
A considerable number of bioactive phytochemicals in foodstuffs have been identified with proven effects modulating tumor growth, progression, and metastasis. The use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products.
Lung, breast, prostate, and colon cancers have the highest overall incidence and represent 36.4% of the total diagnoses. Besides their high occurrence, these types of cancer add up to a mortality rate that reaches 49.2% of the diagnosed cases. Many papers address the association between gene regulation and cancer progression or metastasis, still representing the main approach in cancer research.
Advances in Understanding Specific Cancers
Lung Cancer: Survival is the foremost concern in lung cancer due to its progressive metastasis and resistance to therapy. A 17-gene panel involving critical cellular processes such as hypoxia-mediated epithelial-mesenchymal transition (EMT) or epigenetic modifications was identified as a potential biomarker tool for prediction of metastasis and prognosis in patients affected by non-small-cell lung cancer (NSCLC). Additionally, increasing findings in immunotherapy open expectations for the improvement of the prognosis of lung cancer patients.
Breast Cancer: Tumor heterogeneity makes patient classification according to their risk of metastatic relapse essential in order to guide decisions in adjuvant chemotherapy. Complementary multi-omic studies are emerging as the most promising approaches addressing breast cancer complexity. For instance, a quantitative proteotyping approach based on sequential windowed acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) has been proposed to establish key proteins for breast tumor classification.
Prostate Cancer: The application of new technologies now allows progressing in the understanding of the molecular basis of prostate cancer pathogenesis. Microarray-based transcriptomic analyses and next-generation sequencing technology are examples of powerful tools for studying gene expression and changes in gene structure at the transcript level. Also, these technologies played a critical role in recent studies indicating specific gene fusions, present in at least 50% of prostate tumors, as key modulators of gene expression promoting tumor growth and progression in prostate cancer.
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Colorectal Cancer: Deregulated cellular energetics is another of the hallmarks of cancer. In this sense, cooperative lipid metabolism-related genes involved in colorectal cancer progression have been recently identified. The acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels migratory and invasive properties through EMT induction and is associated with an increased risk of relapse in colorectal cancer patients. Furthermore, the potential correlation between gene polymorphisms and colon cancer progression continues being studied and validated in order to identify prognostic indicators supported by mechanisms such as the increased invasiveness of tumor cells through the expression of genes involved in the activation of fatty acids through conversion to acyl-CoA or the regulation of COX2 expression and cell apoptosis. On the other hand, it has been recently discovered that microbiota plays an important role in colorectal carcinogenesis. This opens up new opportunities for using microbiota profiling information in colorectal cancer prevention, diagnosis, and therapy.
Leukemia: Recent advances in leukemia genomics and epigenomics have facilitated the study of clonal populations and their genetic-epigenetic evolution, changing the classic view of leukemia into a complex heterogeneous disease aggravated by clonal evolution. These findings allow a better understanding of the mechanisms involved in leukemia transformation and therapy resistance and reinforce precision medicine as the most promising approach to leukemia treatment. In the last years, new therapeutic approaches are being investigated, as for instance monoclonal antibodies-based treatments or therapies based in macrophage targeting.
The Role of Precision Nutrition in Cancer Relapse
Cancer recurrence involves many biological interactions, such as genetic, transcription, environmental, endocrine signaling, and metabolism. Lung cancer has a recurrence rate that reaches 50% of patients. Despite having noteworthy advances in recent years on the knowledge of the disease biology and mechanisms of tumor progression, the survival rates remain low and more research is necessary on molecular aspects that give rise to more effective therapies. In respect of leukemia, the high number of relapse-specific mutations acquired by patients affecting genes involved in different functions, leading to clonal evolution and resulting in chemotherapy resistance, points to the high molecular complexity of this process.
Although cancer relapse is due to a multitude of genetic mutations and biochemical processes, advances in genomics, metabolomics, and proteomics allow better understanding of the metabolic diversity due to genetics and microbiome variation, as well as a detailed classification of tumors, which provide precision medicine with individual treatments. Likewise, the best understanding of the metabolic variation allows us to know the interactions between nutrients, metabolism, microbiota, and related genes, facilitating the development of adjuvant cancer therapies based on precision nutrition strategies.
Phytochemicals and Precision Nutrition
Over the years, numerous epidemiological studies have been carried out to link the diet with cancer, either from a preventive approach or by associating the consumption of certain food products with tumor generation and growth. However, in parallel to the development of precision therapies in medicine, precision nutrition is an emerging science that relies on well-established factors such as genetic and epigenetic variation and the microbiome.
The possibility of using nutritional therapies against cancer, as a complementary medicine, is internationally accepted due to its advantages of less toxicity and better acceptance by patients. Recent studies on the association between prevention, treatment, and recurrence of cancer suggest the benefit of investigating the link between specific food components and certain health outcomes. Since very specific therapeutic targets must be reached, precision nutrition must be based on individual foodstuffs with well-established mechanisms of action at the molecular level in terms of gene expression modulation and signaling pathways involved in proliferation, invasion, angiogenesis, and metastasis or apoptosis.
The biological activity of food polyphenols, a broad family of compounds with representatives in virtually all foods, has been specially studied for decades since they have in common an intense antioxidant activity that suggests other potential health outcomes, for example in breast cancer. Recently, intensive research has been carried out to determine the preventive or therapeutic activity of different natural phenolic compounds, opening ways for its application in new treatments of various types of cancers such as breast, colon, or prostate. Some synthetic phenolic compounds have also been successfully studied for the treatment of some cancers. In addition to polyphenols, curcumin (diferuloylmethane) is one of the most studied foodstuffs in recent years as a potential therapeutic product for cancer and more specifically for leukemia. Traditional food products, such as rosemary extract, have been proposed as potential ingredients of precision nutritional supplements in cancer therapy, identifying molecular mechanisms related to the effects and the interactions with currently-used anticancer agents. In the case of colorectal cancer, lipid-metabolism-related genes have acquired relevant interest for precision nutrition therapies, since a wide range of tumorigenic steps can be influenced by lipid metabolism, both in primary tumors and distal metastasis. Certain therapeutic strategies based in diet patterns during adjuvant treatments are also sometimes considered as precision therapies.
Practical Steps for a Cancer-Protective Diet
- Assess your current diet: Determine how much of your current diet comes from whole grains, veggies, fruits, nuts, and seeds, and how much comes from meat and processed foods.
- Set realistic goals: Choose a small first step that is realistic for you and one you can make successfully.
- Increase fruit and vegetable intake: Eat the rainbow daily or weekly to add more color to your diet. Snack on healthy foods, such as fruits, vegetables, nuts, and seeds.
- Reduce red and processed meats: Choose fish, seafood, or poultry, or go meatless more often. There are many great plant-based protein options such as beans, lentils, peas, and tofu.
- Choose whole grains: Opt for whole grains or other whole food carbohydrates rather than processed carbohydrates at meals. Try spaghetti squash or veggie noodles instead of pasta.
- Eat salad as your meal.
- Eat no more than 18 ounces of red meat per week. Avoid burning or charring your meat because it creates compounds in the meat that have been linked to cancer. Use slow, low temperature cooking methods like baking or roasting.
Specific Foods for Cancer Prevention
Here is a list of top cancer-fighting foods that can be included in your cancer prevention diet:
- Leafy greens: Carotenoids found in leafy vegetables such as spinach and kale act as antioxidants and boost the body’s own defenses.
- Whole grains: Whole grains such as oats, barley, and quinoa provide fiber, which can help reduce the risk of developing colorectal cancer. They also help stop free radical damage.
- Soy foods: Limited but suggestive evidence supports the potential for greater overall breast cancer survival and perhaps decreased breast cancer recurrence in women who eat soy-based foods, such as tofu and edamame.
- Walnuts: All nuts contain beneficial cancer-fighting nutrients. Walnuts have been specifically researched because they contain ellagitannins, melatonin, and gamma- tocopherol, which help reduce oxidative stress, inflammation, and gene expression that can lead to certain cancers.
- Pulses: Beans and lentils contain fiber, resistant starch, and phenolic compounds, which may support the growth of health-promoting gut bacteria.
- Citrus fruits: Lemons, oranges, and other citrus fruits provide phytochemicals and vitamins that act as antioxidants and help protect against cell damage.
- Berries: The phytochemicals and nutrients in berries show potential anti-cancer effects in laboratory studies.
- Cruciferous vegetables such as broccoli and cauliflower: Glucosinolates in these vegetables may help thwart the development and progression of certain cancers.
- Coffee: Phytochemicals in coffee are linked to a lower risk of developing endometrial and liver cancers.
- Tea: Limited evidence suggests that tea may decrease the risk of bladder cancer. This refers specifically to black or green tea, not to herbal teas such as peppermint or camomile.
The Importance of Weight Management
Maintaining a healthy weight is one of the most important things you can do to reduce your risk of cancer and other chronic diseases. Body Mass Index (BMI) is a tool to help you determine if you are a healthy weight.
Breast Cancer and Diet
About 30 percent of postmenopausal breast cancer diagnoses are linked to modifiable risk factors such as diet, according to the American Cancer Society. Other studies have shown that as many as 50 to 70 percent of breast cancers can be prevented depending on when people make healthy lifestyle changes. Scientists are still unraveling the relationship between breast cancer and diet, so there is no agreed-upon “breast cancer diet” shown to prevent the disease or improve outcomes in those who have it.
A 2020 study conducted by BCRF investigator Dr. Eating a balanced, healthy diet also has other benefits, too. A healthy lifestyle is linked with lower levels of inflammation, and studies suggest that certain nutrients, vitamins, and compounds have anti-cancer properties that may help lower your risk of breast cancer.
Combining good breast cancer nutrition with exercise may also have a significant impact on outcomes. A recent study conducted by BCRF researcher Dr. Melinda Irwin showed that following an exercise program and a diet high in fruits, vegetables, and fiber and low in sugar and processed foods was associated with a greater pathological complete response (pCR) in patients with hormone receptor (HR)-positive/HER2-negative and triple-negative breast cancer undergoing presurgical chemotherapy.
Foods to Limit for Breast Cancer Prevention
- Saturated fat and trans fats: Foods high in saturated fat, particularly high-fat dairy products such as butter and cheese,may increase breast cancer mortality. Other foods high in saturated fat include beef, lamb, pork, poultry (especially with skin); lard; coconut oil and palm oil; and many baked and fried foods (such as fast food).
- Alcohol: Experts know that drinking any type of alcohol (beer, wine, liquor) raises the risk of breast cancer, but alcohol may also have detrimental effects on breast cancer patients.
- Foods high in added sugar: The rumor that sugar “feeds” cancer isn’t true, but it is wise to limit foods high in added sugars like high-fructose corn syrup, because they’re typically high in calories and contribute to weight gain, insulin resistance, and inflammation. Obvious sources of added sugar include desserts (candy, cookies, pies, cake), juice, and soda.
The DIANA-5 Trial and Breast Cancer Recurrence
The DIANA -5 study revealed that over the span of five years, there was no overall effect of intervention on breast cancer recurrence rates. However, additional analysis based on the level of adherence to the diet showed some interesting details: women in the top tertile of measured adherence to the diet at one year experienced a 41% reduction in their risk of cancer coming back, compared to those who did not stick to the diet. This review revealed that diets abundant in vegetables, fruits, whole grains, and fish, while being low in saturated fats, red meats, processed foods, and sugars are linked to a decreased likelihood of breast cancer recurrence. The review suggested that a modest increase in isoflavone intake - a mere 2 mg per day - could potentially decrease deaths specifically related to breast cancer by 17% and lower the chances of recurrence by a notable 25%.
Diet and Exercise Interventions for Breast Cancer Survivors
With recent medical advances in diagnosis and treatment, the increasing numbers of long-term survivors of breast cancer is considerable and has resulted in the expansion of scientific research to include examination of lifestyle modifications as means of prevention of recurrence, new breast cancer events, and mortality. Considerable evidence exists for the role of healthy eating in breast cancer prevention, while the body of support for the effects of diet on the risk of breast cancer recurrence is rapidly growing.
The Women’s Intervention Nutrition Study (WINS)
The Women’s Intervention Nutrition Study (WINS; n = 2437) was the first of two large, multicenter RCTs employing a low-fat dietary intervention to promote relapse-free survival in women with early-stage breast cancer. In WINS, women aged 48-79, who had completed conventional primary treatment for early-stage breast cancer including surgery, radiotherapy, tamoxifen for estrogen receptor (ER)-positive tumors, and chemotherapy for ER-negative tumors, were recruited within 1 year of diagnosis. After a median of 60 months, only 9.8 % of women in the diet group had reported a recurrence event compared to 12.4 % of women in the control group, with a hazard ratio for relapse-free survival, defined as recurrence at any site, of 0.76 (95 % CI, 0.60 to 0.98; p = .034). As statistically significant weight loss was observed in the intervention group compared to the control group (p = .005), the dietary intervention was purported to lower the risk of recurrence through reductions in body weight.
The physiological basis for the relationship between a high-fat diet and breast cancer recurrence has been attributed to higher body adiposity and the modulatory effects of dietary fats on eicosanoid synthesis. Higher adiposity is associated with adverse levels of insulin-like growth factor 1 (IGF-1), inflammatory markers and sex hormones, all of which may act to promote tumor development and growth. The accumulation of adipose tissue, specifically visceral fat, increases circulating levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and transforming growth factor beta (TGF-β), and the pro-inflammatory adipokine, leptin, which are secreted from the adipose tissue itself.
The Women’s Healthy Eating and Living Study (WHEL)
Similar to the WINS, the WHEL study was driven by early epidemiological evidence suggesting a lower risk of breast cancer with a low-fat diet, which the investigators combined with preclinical evidence supporting the anticarcinogenic properties of plant-derived foods. The WHEL study (n = 3088) recruited women aged 18-70 diagnosed with operable invasive breast carcinoma (AJCC version VI Stage I, II or III) who had completed surgery and radiotherapy but not chemotherapy. Over the mean 7.3-year follow-up, the authors concluded that a low-fat, high vegetable, and fruit intake diet did not reduce recurrence events or provide survival benefit to women with early-stage breast cancer.
The postulated mechanisms underlying a high intake of fruits and vegetables in reducing the risk of recurrence are related to the role of plant-derived foods as a source of chemopreventive compounds and having the ability to lower circulating estrogen concentrations. The anticarcinogenic properties of such a dietary pattern have been attributed to high levels of phytonutrients, including carotenoids, polyphenols, and isothiocyanates.
Soy Intake and Breast Cancer Recurrence
Conflicting data exists between epidemiological and preclinical investigations on the role of soy intake in breast cancer recurrence. While the epidemiological data has found no association between soy intake and adverse breast cancer events, the in vitro and in vivo data have raised concerns on the safety of phytoestrogens in breast cancer survival. However, the concerns surrounding the relationship between genistein and breast tumor proliferation have been questioned in a recent review, with evidence cited to support the anticarcinogenic effects of genistein while disputing its stimulatory effects. In contrast, the epidemiological data unequivocally refutes the dangers of isoflavones in breast recurrence, with data from 4 large clinical trials reporting no adverse relationship between soy intake and breast cancer prognosis.