There is exciting news in the world of cancer nutrition! For years, the triple negative breast cancer patient has been without a targeted treatment. But, the evidence is beginning to show that some triple-negative specific targeted treatment is on the horizon.
This is great news for you if you want to take back the control cancer has taken from you and reduce your fear around this diagnosis—you are not powerless! This is new information in the triple-negative breast cancer community and it will help you to be an active participant in your cancer treatment.
Whether you are a breast cancer patient or survivor or are dealing with another type of cancer, let’s take a look at what these new studies might mean for you…
What is Triple Negative Breast Cancer?
When a cancer is diagnosed, it undergoes laboratory analysis to determine the exact type of cancer and its receptors. In the case of breast cancer, there are currently several different receptors that have been identified. These are:
Estrogen Receptor Positive (ER+)
- Estrogen drives the growth of this cancer so treatment includes blocking estrogen and/or shutting down production of estrogen.
Progesterone Receptor Positive (PR+)
- Similar treatments are used for PR+ as are used for ER+ including hormone therapy such as Tamoxifen and Aromatase Inhibitors.
- There was a win for the breast cancer community in the mid-1980s with the discovery of a protein called Human Epidermal Growth Factor (HER), which resulted in a subsequent benefit for patients with this very aggressive breast cancer. Herceptin, a drug that targets this gene was first tested on 15 women in the summer of 1992 and is now standard treatment for HER-2/Neu positive breast cancers.
- When pathologists test an individual’s breast cancer cell biopsy, some are negative for estrogen receptors, negative for progesterone receptors, and negative for HER-2/neu receptors. It is therefore referred to as “triple negative”.
Triple Negative Breast Cancer is Harder to Treat
The type of cancer cell found in Triple Negative Breast Cancer is more common in women with BRCA1 gene mutations, younger women, African-Americans and Hispanics. Triple Negative Breast Cancer makes up about 15% of breast cancer cases and is more difficult to treat because it lacks a specific target.
Since it is more difficult to treat, people with this diagnosis can be especially fearful and also feel there isn’t much they can do to help themselves fight against this cancer. I want to share some information about a scientific evidence and new clinical trials to show you that triple negative patients may not be as powerless as they once thought.
What is Methionine Depletion?
Could something called “methionine depletion” provide the target that is needed for triple negative cancers? Methionine is an amino acid that is part of our diet. Researchers at the University of Wisconsin conducted experiments to see how cancer behaves when this amino acid is removed from the diet. This study was conducted in a laboratory with triple negative breast cancer cells in a petri dish (1).
How Were Triple Negative Breast Cancer Cells Deprived of Methionine?
Researchers at the University of Wisconsin worked with triple negative breast cancer cells, growing these cells in 1 of 2 different cultures in the lab. One normal culture, called a “control” and one culture that was deficient in the amino acid, methionine. Three different cell types (MDAMB-468, GILM2 and MDA-MB-231) were treated with seven different cancer drugs including lexatumumab.
What Happened When Triple Negative Breast Cancer Cells Were Deprived of Methionine?
The cell culture that was deficient in the amino acid, methionine, was found to be moderately toxic to the cancer cells and inhibited their proliferation. The combination of growing cancer cells in the methionine deficient culture plus the drug lexatumumab was the only combination that showed enhanced cancer cell toxicity in all three cancer cell types. A second experiment in which a methionine degrading enzyme (methioninase) showed that this also made lexatumumab more effective.
While the human body is far more complex than cells in a petri dish, this experiment gives us a hypothesis…Since restricting methionine for isolated cancer cells is toxic, restricting methionine from the diet of a cancer patient could help to kill cancer cells, reduce their proliferation and make the drug lexatumumab more effective. The next step to testing this hypothesis is an animal model.
Methionine Restricted Diet in Mice with Breast Cancer
Because of the results of the cell studies, the same researchers from the University of Wisconsin tested the methionine restricted diet in mice with breast cancer. The following treatments were used on the mice: control group, methionine-free diet alone, lexatumumab alone, and methionine-free diet plus lexatumumab (1).
What Happens with you Put Mice with Triple Negative Breast Cancer on a Methionine-Restricted Diet?
All three treatments: methionine-free diet alone, lexatumumab alone or methionine-free diet plus lexatumumab inhibited tumor growth compared to the control group. The best result though was in the mice given the combination of the methionine-free diet plus lexatumumab. This group of mice (given methionine-free diet plus lexatumumab) also had less lung metastasis. In fact, the methionine-free diet plus lexatumumab combination was even better at reducing metastases than it was at inhibiting the tumor growth.
Testing Methionine Restricted Diet in Women with Triple Negative Breast Cancer
The University of Wisconsin researchers state in the publication of the research that “our findings provide proof-of-principle preclinical evidence to support a clinical trial combining dietary methionine restriction and [cancer drugs].” Those trials are now underway…
Human Trials of Methionine-Free Diet
Since I originally published this blog back in 2015, there are now two trials underway. Let me tell you about them…
The first study is called:
A Window of Opportunity Study of Methionine Deprivation in Triple Negative Breast Cancer
In this study, women with newly diagnosed triple negative breast cancer consume a methionine-free beverage plus low methionine foods for 1 to 3 weeks prior to surgery or chemotherapy at the University of Wisconsin Carbone Cancer Center. This study is currently recruiting. Read more about it here:
The second study is called:
ONC201 With and Without Methionine-Restricted Diet in Patients With Metastatic Triple Negative Breast Cancer
In the second study, women with metastatic triple negative breast cancer, go on a methionine-restricted diet. This study is also recruiting. You can read more about this trial here:
Should I Go On A Methionine-Free Diet?
It’s too early in the research process to prescribe a methionine-free diet for triple negative breast cancer. However, a study was performed on eight patients with metastatic cancer done to test whether a methionine-free diet might be safe. The patients were given a very low protein, low methionine diet for an average of 17 weeks and it was found to be safe (2).
What if I Don’t Want to Wait for the Results of the Clinical Trials?
I certainly understand if you as a cancer patient or survivor do not want to wait for a clinical trial to finish and the results to be published. I know many of you want to be actively fighting against your cancer and doing everything you can.
So, I want to provide you with some additional information about methionine and a low methionine diet. Since studies have shown a low methionine diet is safe and we know plant-based diets are safe and healthy, following a low methionine diet could be just what you need to help you feel that you are doing more to help reduce your cancer and it’s spread. By actively participating in your care in this way, it can help to give you back some control and reduce some of your fear.
What is Methionine?
Methionine is an essential amino acid. These are the building blocks of protein that we must consume in our diet to maintain our health. It is ‘essential’ meaning that we can’t make it in our bodies, but must consume it in our diet.
What Foods Contain Methionine?
The top 100 methionine containing foods are all animal proteins. Turkey has 1.5 g of methionine per 3 oz (90 g) serving followed by (in descending order) whelk (snails), eggs, cottage cheese, beef, chicken, sturgeon, veal, tuna, pork, lamb, quail and pheasant (3).
Top 500 Methionine-Containing Foods
The top 500 methionine-containing foods include all manner of animal proteins including game meat, goose, ostrich, halibut, trout, snapper, milkfish, duck, mackerel, salmon, swordfish, haddock, parmesan cheese, Pollock, perch, grouper, burbot, mollusks, pike, snapper, herring, tilefish, anchovy, ling, flatfish (flounder, sole or plaice), bluefish, rickfish, tilapia, roe, followed by the final entry out of 500 which is ground chicken with 0.45 g of methionine in a 75 g serving. Use this link to see a list of foods that ranked from highest to lowest in methionine (see below for instructions on using this database).
What Constitutes A Methionine Restriction?
In one study on the topic of methionine-restricted diet, the researchers used 2 mg of methionine per kg of body weight (2). Let’s calculate this by plugging in our body weight to the calculations below.
Methionine Calculations With Example
Step 1. How much do you weigh? 132 lbs
Step 2. Convert your weight in lbs to kg by dividing your weight in lbs by 2.2 = 60 kg
Step 3. Multiply the methionine level used in the study (2 mg) X your weight in kg (60 kg) = 120 mg
Step 4. Convert mg to g by dividing by 1000 (120/1000) = 0.12 g
As I mentioned above, a 75 g serving (2 ½ oz) of ground chicken had 0.45 g of methionine. So, you can see, that this would already be over the limit of 0.12 g per day. Substitute your weight into the above formula to find your limit.
How Do I Achieve a Low Methionine Diet?
Choosing a diet that is low in animal protein such as a plant-based would lessen your methionine intake. Until more research is known about the actual level of methionine intake necessary and what cancer types and subtypes are more adversely affected by methionine restriction, and what drug regime is made more effective by methionine restriction, it’s hard to get any more detailed at this time. But, in the meantime, I still think this study is relevant for you as a cancer patient and survivor, including newly diagnosed and metastatic.
Why Are These Studies Relevant for A Triple Negative Cancer Patient?
These studies provide early evidence that nutrition can play a key role both by itself and combined with drug therapy (lexatumumab) to make cancer cells more vulnerable. This is especially relevant for the cells lines that were tested in the study—namely triple negative breast cancer cells (MDAMB-468, GILM2 and MDA-MB-231) . Being able to be part of your care team by following a therapeutic diet will help to keep you in the drivers seat of your own cancer care. Taking back control and maintaining control of aspects of your life, such as your diet, is a big part of being a cancer thriver.
Plant-Based Diets for Cancer Treatment
This study provides more evidence that a plant-based diet is best for cancer patients. It also provides an interesting slant that plant-based diets may not just be useful for cancer prevention but also can be a treatment by itself and to make cancer treatment with lexatumumab more effective. These studies have peaked my interest in this topic so I plan to continue to follow it and update you with new teachings. To make sure you don’t miss out, I invite you to join my subscriber list where you will receive a link to my monthly blog and information about when and were I am speaking.
Join the Conversation
Do you have triple negative breast cancer? Are you being treated with lexatumumab? Have you been told by your medical professional about a low-methionine diet? I’d love to read your comments below or on Facebook here.
Looking for Additional Reading on this Topic?
References or Methionine Restricted Diet and Triple Negative Breast Cancer
(1) Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression Clin Cancer Res. 2015 Jun 15;21(12):2780-91. Strekalova E1 et al.
Instruction on how to use the USDA Food Composition Tables.
To search for methionine content of foods:
- From the https://ndb.nal.usda.gov/ndb/ home page click “start your search here”
- Click “nutrient search”
- For “First Nutrient” choose “methionine” from the drop down menu (not in alpha order)
- Choose either ‘all foods” or “abridge” and then choose either “per 100 g” or “household measure” , choose sort by “nutrient content” this will sort from highest to lowest
- Hit “go”
- You can also use this link where I have done that already and you can read the list of methionine content of foods from highest to lowest.