I’ve been getting an increasing amount of questions about whether collagen supplements are safe for breast cancer survivors, and indeed, I’ve run across a few articles lately warning us about collagen supplementation. So today’s article is dedicated to shedding some light on the subject, and hopefully answering that question.
If you’ve noticed, there are a number of companies promoting collagen supplements at the moment. They are promoting it hard – like a new wonder drug – for better skin and nails, better hair (which I suspect is the reason people are asking me about collagen, to help them with hair loss due to breast cancer treatments), better gut health, for weight loss, and for its so-called anti-aging benefits.
But is it safe for breast cancer survivors? At first glance, one would think, well why not? If it’s already in our bodies, why wouldn’t it be safe?
Let’s look a little deeper into this.
The Role of Collagen
Collagen is a long chain of proteins and sugars (known as a glycoprotein), and is the most abundant protein within our bodies. Collagen is found in skin, hair, cartilage, and many other tissues, and it is absolutely vital. Collagen is also the major component of something called the extracellular matrix, or ECM.
The ECM is a network of molecules such as collagen, enzymes, fibers, proteins and glycoproteins that exist outside of our cells – sort of like a scaffold, in order to support the cells with which they are associated. The ECM provides structural and biochemical support to the cells surrounding the ECM and there is an interaction between cells and the ECM – it helps to inform cells about growth and many other functions. 
The interaction between cells and the ECM provides for things like regulation of gene expression, cell differentiation and growth. So far so good. But this interaction between the ECM and cells can also play an important role in the growth of a tumor and its ability to grow and spread.
According to Sara Musetti, scientist and co-founder of OncoBites, a cancer research outreach blog, cancer takes all the good things about collagen and turns them into a nightmare. Musetti tells us “Collagen is used to support and protect, so naturally tumors twist it to their advantage. Tumors are often full of fibroblasts, the major cell type responsible for producing collagen. These cells pump out huge amounts of collagen, swaddling little pockets of tumor cells, called tumor nests, in blankets of collagen that keep damaging agents away. These collagen-rich regions form a physical barrier around tumor cells that keep chemotherapeutics, immune cells, antibodies, and other therapies from reaching the cells to kill them. The particular shape and character of collagen in a tumor has even been linked to how easily the tumor grows and spreads.” 
I found that fascinating – this ability of collagen to hide tumor cells in protective pockets so that immune cells and chemo drugs can’t get to them.
A 2013 study  found that DDR2, a protein that sits on the surface of tumor cells and binds to collagen, activates a pathway that encourages the spread and invasiveness of tumor cells. Researchers stated that DDR2 might very well be a good therapeutic target for treating metastasized breast cancer.
A 2014 paper  in Tumour Biology stated “While collagen was traditionally regarded as a passive barrier to resist tumor cells, it is now evident that collagen is also actively involved in promoting tumor progression. Collagen changes in tumor microenvironment release biomechanical signals, which are sensed by both tumor cells and stromal cells, trigger a cascade of biological events. In this work, we discuss how collagen can be a double-edged sword in tumor progression, both inhibiting and promoting tumor progression at different stages of cancer development.”
Another 2014 paper  stated that both hyaluronan (another glycoprotein found in the ECM) and collagen VI are upregulated (promoted) in breast cancer, generating a microenvironment that promotes the progression of a tumor and also metastasis.
In her 2015 YouTube video “Understanding the Role of Collagen in Breast Cancer” , Dr Patricia Kelly explains that breast cancer cells use the collagen network in order to travel to other parts of the body.
A 2016 article in Science Signaling  stated that TM4SF1 (a protein encoded by the gene TM4SF1) promoted the reactivation of dormant breast cancer cells in the lung, bone, and brain by promoting signaling when cells came into contact with type I collagen. Also, high TM4SF1 expression correlated with reduced metastasis-free survival in breast cancer patients, and that for those who had high expression of TM4SF1, this was highly predictive of their breast cancer recurrence.
Interestingly, it appears that different types of collagen can also suppress tumor growth. A 2015 animal study  found that type III collagen (col3) suppressed the carcinogenic microenvironment of a developing tumor. That was the only study I found that showed a particular type of collagen suppressed tumor growth.
A 2018 study  found that type 1 collagen promoted breast cancer cell growth and the ability to migrate to distant parts of the body.
Another 2018 study  also showed that collagen type 1A1 promoted breast cancer metastasis.
A 2018 article published in Breast Cancer Research  stated “Increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients.” The focus of the study was on a type of collagen known as collagen XIII. It was found that expression of this form of collagen was significantly higher in human breast cancer tissue compared with normal, healthy breast tissue, and that increased collagen XIII levels in breast cancer tissue correlated with increased tumor recurrence, promoted invasive tumor growth and enhanced breast cancer cells.
A 2019 review of medical studies on collagen  called collagen a “double-edged sword” with regard to cancer. The review reiterated the fact that our bodies have lots of collagen and require it for proper functioning. However, collagen is the major component of the tumor microenvironment and has been shown to participate in cancer development. Cancer cells use and reshape collagen, utilizing it to improve invasiveness, increase the ability of cancer cells to resist dying off, for building new blood vessels (angiogenesis), and many other functions, which gradually promotes cancer progression. Also, collagen-rich environments lack oxygen (known as hypoxia), which intensifies cancer progression.
The study at  concluded: “Cells and molecules in the tumor microenvironment have dual effects on cancer progression. The role of collagen is a double-edged sword in cancer. On the one hand, collagen, cancer cells, other cells, and other matrix molecules mutually form an inter-reinforcing loop. This loop contributes to the development of cancer by inducing cancer cells proliferation, migration, and metastasis. On the other hand, preclinical and clinical studies have demonstrated that collagen may slow the development of cancer cells to some extent under some conditions. In summary, the association of collagen with cancer is only partially understood, and future studies are needed to elucidate detailed collagen biological mechanisms in cancer tissue that can be applied to precisely regulate collagen balance to achieve the maximum benefit of treatment. This new strategy combined with other treatment modalities can ultimately improve patient survival and quality of life.”
One Chinese doctor at a burns unit in a Beijing Hospital (who did not wish to be named) clearly held a dim view of collagen supplementation, calling them absolutely useless. He said that after digestion, collagen disintegrates into amino acids, which are also found in the proteins of commonly-consumed foods like eggs, meat and beans. “The best result you can hope for after eating collagen is no effect,” the doctor said. “It would be more dangerous if you found the collagen effective, because then estrogen must have been added to the product.”
The Bottom Line
It is clear that researchers believe that many types of collagen promote tumor growth. Because it has been observed that breast cancer patients with high levels of collagen in their tumors often have less than optimal outcomes, it is advisable to steer clear of collagen supplementation if you have active cancer tumors in your body.
Because we do not have a definitive answer on whether collagen supplementation is safe for those whose tumors are gone, here’s what I would recommend.
Until we understand more about collagen supplementation, I intend to live by this quotation by wise old Benjamin Franklin: “When in doubt, don’t”.
If you are considered to be cancer free and you believe collagen will be of benefit to you, and your doctor agrees with that, proceed with caution. I don’t believe women with dense breasts should supplement with collagen, as high collagen levels are the reason for increased breast density and are related to higher breast cancer risk. 
 Video: Extracellular Matrix: https://www.khanacademy.org/science/biology/structure-of-a-cell/cytoskeleton-junctions-and-extracellular-structures/v/extracellular-matrix
 Article: The Double-Edged Sword of Collagen — https://oncobites.blog/2019/12/06/the-double-edged-sword-of-collagen/
 The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis — https://www.nature.com/articles/ncb2743
 Collagen as a double-edged sword in tumor progression – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980040/
 Collagen VI and Hyaluronan: The Common Role in Breast Cancer – https://www.hindawi.com/journals/bmri/2014/606458/
 Video: Understanding the Role of Collagen in Breast Cancer – https://youtu.be/uAHpvwv9iqg
 Cancer reactivated by collagen – https://stke.sciencemag.org/content/9/437/ec165
 Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer — https://www.sciencedirect.com/science/article/pii/S0002944015001285
 Collagen type 1 promotes survival of human breast cancer cells by overexpressing Kv10.1 potassium and Orai1 calcium channels through DDR1-dependent pathway – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973854/
 Collagen – col1A1 – Promotes Metastasis of Breast Cancer and is a Potential Therapeutic Target —
 Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance – https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-1030-y#:~:text=Increased%20collagen%20expression%20and%20deposition,protein%20within%20the%20collagen%20superfamily.
 The role of collagen in cancer: from bench to bedside – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744664/
 Collagen Matrix Density Drives the Metabolic Shift in Breast Cancer Cells – https://www.sciencedirect.com/science/article/pii/S2352396416304674