Metastatic breast cancer is advanced cancer that has spread to other parts of the body beyond the breast tissue, and has a very poor prognosis. Treatment for metastatic breast malignant neoplasm is moving towards personalization based on cancer characteristics. A similar personalization of nutrition recommendation based on cancer characteristics and treatment is lacking and much needed to improve the odds of success and quality of life of the cancer patient. This blog highlights the needs, gaps and examples of personalized nutrition/diet for metastatic breast cancer.
Breast Cancer Basics
Breast cancer is the most commonly diagnosed cancer and one of the leading causes of cancer-related death in women globally. One of the most common subtypes of breast cancer is the sex hormone dependent, estrogen (ER) and progesterone (PR) receptor positive and human epidermal growth factor 2 (ERBB2, also called HER2) negative – (ER+/PR+/HER2- subtype). The hormone positive subtype of breast cancer has a good prognosis with a very high 5-year survival rate of 94-99% (Waks and Winer, JAMA, 2019). The other types of breast cancer are the hormone receptor negative, HER2 positive subtype and the triple negative breast cancer (TNBC) subtype that is ER, PR and HER2 negative. The TNBC subtype has the worst prognosis and the highest probability of advancing to late stage disease that has metastasized and spread to other parts of the body..
Metastatic Breast Cancer is the very advanced, stage IV cancer that has spread to other parts of the body (most often the bones, lungs, liver or brain). There are only 6% of women who are diagnosed with metastatic breast malignant neoplasm at first diagnosis. Most other cases of invasive or metastatic breast malignant neoplasm is when the cancer has relapsed in the patient after completing prior treatment and being in remission for many years. Metastatic breast cancer, mostly prevalent in women but also found in a small percentage of men, has a very poor prognosis with a 5-year survival being less than 30% as per data from the American Cancer Society Publication (Cancer Facts and Figures, 2019). The median overall survival of metastatic TNBC is only 1 year when compared to 5 years for the other two subtypes. (Waks AG and Winer EP, JAMA 2019)
Treatment Options for Metastatic Breast Cancer
Metastatic breast cancer is treated with many different therapy regimens including different classes of chemotherapy, immunotherapy, targeted therapy, hormonal therapy and radiation therapy options, through a trial and error process, since there is no defined treatment for this cancer. Treatment choice is dependent on the molecular characteristics of the prior breast cancer cells, past breast cancer treatments, clinical status of the patient and where the cancer has spread.
If breast cancer has spread to the bones, then along with the endocrine therapy, chemotherapy or targeted therapy, the patient is also treated with bone modifying agents such as bisphosphonates. These help with palliative care but have not shown to improve overall survival.
If hormone positive breast cancer has advanced to metastatic stage IV disease, the patients are treated with extended endocrine therapy with agents that modulate or inhibit estrogen receptors, or prevent production of estrogen in the body. The endocrine therapy, if ineffective, is used in combination with other chemotherapy drugs or targeted drugs such as the cell cycle kinase inhibitors or drugs targeting specific internal signaling hotspots, based on the molecular and genomic characteristics of the cancer.
For hormone negative, HER2 positive, metastatic breast cancer, a key treatment option is the HER2 targeted antibody drugs or small molecule inhibitors. These are combined with other chemotherapy drugs.
However, for TNBC metastatic cancers with the worst prognosis, there are no defined treatment options. It is based on the presence of other key mutations in this subtype of cancer. In case of BRCA mutant cancers, they are treated with poly-ADP ribose (PARP) inhibitors. If these cancers have expression of immune checkpoints, they could be treated with immunotherapy drugs such as immune checkpoint inhibitors. Else, these patients are treated with very aggressive chemotherapy options such as platinum drugs (Cisplatin, Carboplatin), adriamycin (Doxorubicin), taxol drugs (Paclitaxel), topoisomerase inhibitors (Irinotecan, Etoposide) and various different permutations and combinations of these, to control the spread of the disease. Combination chemotherapy used for metastatic breast cancer treatment however has very high toxicity and a significant negative impact on quality of life of the patients.
Need for Personalized Nutritional Recommendations for Cancer Patients
A cancer diagnosis in itself is a life-changing event associated with anxiety of the impending treatment journey and fear of the uncertainty of the outcome. After being diagnosed with cancer, patients are motivated to make life-style changes that they believe will improve their health and well being, reduce the risk of recurrence, and reduce the side-effects of their chemotherapy treatments. Often, they start using dietary supplements randomly, along with their chemotherapy treatments, to help reduce the very severe side-effects and improve their general health and well being. There are reports of 67-87% of cancer patients that use dietary supplements post diagnosis. (Velicer CM et al, J Clin. Oncol., 2008)
However, nutritional and dietary recommendations for cancer patients today are not personalized. Despite the advances in genomics, metabolomics, proteomics that have improved our understanding of the cancer characteristics and enabling precision treatment approaches, nutritional guidance if any is very generic. The nutritional guidance is not based on the specific cancer type and genetic characteristics of the cancer, or the type of treatment being given to the patient. The general guidelines for nutrition/diet as recommended by the American Cancer Society include:
- Maintaining a healthy weight;
- Adopting a physically active lifestyle;
- Consuming a healthy diet with an emphasis on plant sources; and
- Limiting alcohol consumption.
Treatment options for different cancers are evidence-based and recommended by different cancer society guidelines such as the National Comprehensive Cancer Network (NCCN) or American Cancer Society (ACS). Evidence that is obtained for drugs is based on large randomized clinical trials (RCTs). Many treatments are targeted to specific cancer genomic characteristics. Despite that, for many advanced cancers such as metastatic TNBC, there are still no standard guidelines and treatment regimens that are known to be effective. Treatment for this subtype is still based on trial and error approaches.
However, there are no such evidence based guidelines for personalized nutrition/diet recommendations. There is a paucity of RCTs to generate evidence for developing nutrition recommendations and dietary guidelines to complement different cancer types and treatments. This is a big gap that we currently have in our cancer care today. Despite the increasing knowledge of nutrition gene interactions, the complexities of nutrient actions and interactions are difficult to adequately address through any single RCT research design. (Blumberg J et al, Nutr. Rev, 2010)
Due to this limitation, the level of evidence for nutrition support and confidence for defining nutrition/diet requirements for cancer patients will always be different from that needed for drug evaluation. Additionally, nutrition/diet guidance unlike drug treatments is natural, safe and associated with low to minimal side-effects in most cases. However, personalizing nutritional recommendations for the specific context of cancer type and treatment based on scientific pathway overlaps and a rationale supported by experimental data, although not similar to RCT based evidence, can provide better guidance for patients and enhance integrated cancer care.
As there is heterogeneity even in the cancers and treatments for metastatic malignant neoplasms of the same tissue type, the nutritional recommendations as part of integrative cancer care will also need to be personalized. The right supportive nutrition and more importantly the foods to avoid in specific contexts and during treatment can contribute to improving outcomes.
Benefits of Supportive Nutrition/Diet for Metastatic Breast Cancer
As disease characteristics and treatments for metastatic breast cancer are so varied based on the primary subtype of disease, the requirements for supportive nutrition/diet will also not be one size fits all. It will be dependent on the genetic characteristics of the metastatic breast cancer and the type of treatment being received. Hence genetic factors of the disease, other key characteristics of the individual patients in terms of their body mass index (BMI) to assess obesity levels, lifestyle factors such as physical activity, alcohol intake etc. are all going to be key influencers in designing personalized nutrition that can be supportive and effective in disrupting the cancer at every stage of the disease.
The importance of providing personalized nutrition/diet guidance that is tailored to the specific cancer and treatment, for patients with metastatic breast malignant neoplasms can provide the following benefits: (Wallace TC et al, J. of Amer. Coll. of Nutr., 2019)
- Improve strength and immunity of the patient without interfering with the treatment efficacy.
- Help with reducing the side-effects of the treatments.
- Help with enhancing the ongoing treatment efficacy by choosing foods and supplements that can synergize with the mechanism of action of the ongoing treatment through modulating the appropriate pathways, or inhibit the potential resistance pathways.
- Avoid foods and supplements that could interfere with the ongoing treatment through nutrient drug interactions that could either lower effectiveness or increase toxicity of the treatment.
Examples of Personalized Nutrition/Diet for Metastatic Breast Cancer
The dietary/nutrition recommendations for metastatic hormone positive cancer patients who continue to be on extended endocrine therapy such as Tamoxifen will be very different from other metastatic breast cancer patients.
Examples of Foods/Supplements to Avoid if on treatment with Estrogen Modulators
For patients on estrogen modulators, some examples of foods and supplements they will need to avoid that can interfere with their endocrine treatments along with the scientific rationale are mentioned below:
Curcumin, the active ingredient from the curry spice turmeric, is a natural supplement that is popular among cancer patients and survivors for its anti-cancer and anti-inflammatory properties. Therefore, the likelihood of breast cancer patients taking Curcumin while on Tamoxifen therapy is high.
The oral drug Tamoxifen is metabolized in the body into its pharmacologically active metabolites through the cytochrome P450 enzymes in the liver. Endoxifen is the clinically active metabolite of Tamoxifen, that is the key mediator of efficacy of tamoxifen therapy (Del Re M et al, Pharmacol Res., 2016). A recently published prospective clinical study (EudraCT 2016-004008-71/NTR6149) from the Erasmus MC Cancer Institute in the Netherlands, showed a negative interaction between Curcumin and Tamoxifen in breast cancer patients (Hussaarts KGAM et al, Cancers (Basel), 2019). The results indicated that the concentration of the active metabolite Endoxifen decreased in a statistically significant manner when Tamoxifen was taken along with Curcumin supplement.
Studies such as these cannot be ignored, although in a small number of breast cancer patients, and provide a caution for women taking tamoxifen to choose the natural supplements they take carefully, that do not interfere with the cancer drug efficacy in any way. Based on this evidence, Curcumin does not seem to be the right supplement to be taken along with Tamoxifen. However, this does not mean that curcumin as a spice and flavoring in curries needs to be completely avoided altogether.
DIM (diindolylmethane) Supplement
Another common and widely used supplement amongst breast cancer patients is DIM (diindolylmethane), a metabolite of I3C (Indole-3-carbinol), found in cruciferous vegetables like broccoli, cauliflower, kale, cabbage, brussel sprouts. This popularity of DIM could be based on clinical studies that have shown that an overall high consumption of cruciferous vegetables in the diet/nutrition was significantly associated with a 15% lower risk of breast cancer. (Liu X et al, Breast, 2013) However, a randomized, double-blind, placebo controlled clinical study that tested the use of DIM supplement along with Tamoxifen in breast cancer patients, has shown the alarming trend of tamoxifen active metabolite reduction, thereby the potential for reducing the effectiveness of the endocrine therapy.(NCT01391689) (Thomson CA, Breast Cancer Res. Treat., 2017).
Since the clinical data is showing a trend of interaction between DIM and tamoxifen, breast cancer patients while on tamoxifen therapy should veer on the side of caution and avoid taking DIM supplement. A plant-food based diet rich in cruciferous vegetables may provide the required benefit over taking a supplement of DIM in this context.
Beneficial and Preferred Foods for Metastatic Breast Cancer
There are many foods that are associated with improving outcomes for breast cancer patients. A meta-analysis of multiple prospective studies and RCTs recently published by researchers from Institut Curie in France has reported that a low-fat diet was associated with better survival. Also, a diet that was rich in phytoestrogens from fruits and vegetables, reduced the risk of cancer recurrence. And, a healthy diet with plant based foods was associated with improvement in overall survival and risk of death. (Maumy L et al, Bull Cancer, 2020)
A study published earlier this year tested the impact of ketogenic diet/nutrition on survival of breast cancer patients. They found that a ketogenic diet along with ongoing chemotherapy treatments improved the overall survival with no substantial side-effects in the patients. (Khodabakhshi A, Nutr. Cancer, 2020) A ketogenic diet is an extreme low-carbohydrate diet that aims to promote the metabolism of fats into ketone bodies (rather than carbohydrates into glucose) to provide the main source of energy for the body. Normal cells in our body can transition to using ketone bodies for energy, but cancer cells cannot effectively use ketone bodies for energy due to an abnormal tumor metabolism. This makes the tumor cells more vulnerable and in addition, the ketone bodies reduce tumor angiogenesis and inflammation while enhancing tumor cell death. (Wallace TC et al, J. of Amer. Coll. of Nutr., 2019)
Since very specific therapeutic targets must be reached based on the cancer characteristics and the type of treatment, precision and personalized nutrition must be based on individual foods and supplements with well-established mechanisms of action at the molecular level in terms of their impact on genes and pathways. (Reglero C and Reglero G, Nutrients, 2019)
For example, one way to prevent metastasis of the cancer is to block angiogenesis, the sprouting of new blood vessels, which would also prevent chemotherapy resistance. There are foods and supplements with the bioactive silibinin, such as artichoke and milk thistle, that have scientifically shown to inhibit angiogenesis. Personalized nutrition/diet recommendations of these foods in this context of metastatic breast cancer undergoing chemotherapy, could help in improving effectiveness of the treatment and prevent recurrence. (Binienda A, et al, Anticancer Agents Med Chem, 2019)
Similarly, other key characteristics of the cancer and treatment could be analyzed to find the scientifically right foods and supplements for personalized nutrition design for cancer patients to match their cancer type and treatment.
As treatment recommendations are moving towards personalization based on cancer genomics and molecular cancer characteristics of each patient, integrative cancer care also needs to move towards personalization of supportive nutrition/diet based on the stage and type of cancer and treatment. This is a largely untapped area which can significantly help with improving outcomes and quality of life for the patients with metastatic breast cancer. When in good health, natural foods and supplements do no harm. But, when the context is cancer where the body is already dealing with an internal dysregulation in metabolism and immunity due to the disease and the ongoing treatments, even natural foods, if not chosen correctly, have the potential to cause harm. Therefore, personalization of nutrition based on cancer indication and treatment type can support improved outcomes and well being for the patient.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer.Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.