Tuesday, January 2, 2024

Epigenetic Research Notes: Profiling the Dense Breast Paradigm

Written by: Dr. Roberta Kline

As an Ob-Gyn physician and genomics specialist, I have spent the better part of 10 years translating research in the genomic and gene expression areas into clinically usable information for healthcare professionals. One of the biggest challenges we face when connecting research with patient care is the long delay in the translation process and dissemination of the information. It often takes 10 to 20 years for information (validated findings) that comes out of research to be applied in clinical practice. These delays result in many lost opportunities to provide better care for our patients. This is one of the reasons why I'm really passionate about accelerating this process and making it easier for clinicians and their patients to take advantage of cutting-edge information and new technologies. 


LINKING DENSE BREAST WITH BREAST CANCER
We have known for a very long time that there is an increased risk of breast cancer for women who have dense breasts. Until recently, the research has been lagging in terms of what's the molecular mechanism, why do dense breasts present an increased risk of breast cancer? Without this knowledge, we can’t address the root causes, and are left with a lot of trial and error based on incomplete understanding. 

It's very encouraging to know that currently there are 124 clinical trials ongoing looking at dense breasts and the relationship with breast cancer, anywhere from improved diagnostics, to treatment, to prevention, and, what’s close to my heart, to understanding the molecular mechanisms - what's happening at the cell level, at the genetic level that is causing different women to have an elevated risk of breast cancer. 

One of the striking features that we're learning about dense breasts and what is creating that density is the microenvironment, which means the environment in the supporting tissue surrounding the glands. This includes fibroblasts and collagen. It seems that rather than estrogen being the dominant factor, it is inflammation that is creating the increased density of breast tissue. 


ESTROGEN VS INFLAMMATION
What's fascinating to me is that even though we associate estrogen with the primary means by which women develop breast cancer, it may be a different process for breast cancers linked to breast density. Some of the research that has just come out in the last few years is showing us that rather than being hormonally driven, we think what's happening is there is an increase in these inflammatory markers in the tissue that is denser, and this is what can also lead to cancer.

There is clearly a genetic, or hereditary component, because having dense breasts is noted to run in families. But while having dense breasts increases a woman’s risk of breast cancer by up to 4-6x, not all of these women actually get cancer. That means there are other factors that can potentially increase as well as reduce a woman’s risk. This is where genomic research has been a gamechanger in identifying these other factors including for women with inherited genetic mutations, such as BRCA. 

We now know that there are multiple genes in multiple other pathways that can modify a woman’s risk of breast cancer even if she carries a BRCA mutation. [1]. Researchers have identified smaller changes in genes called SNPs (single nucleotide polymorphisms) that have a much lower individual impact than genetic mutations, but together can be additive.[2] In fact, women with specific patterns of SNPs had their risk of breast cancer significantly reduced. This can help explain why not all women with BRCA mutations get cancer, and provides insight into potential protective biological mechanisms.

This is a really powerful paradigm shift, because now it opens the door for truly individualizing each woman’s risk – and potentially being able to change it through diet, lifestyle, or other modalities.

We now are also learning that gene SNPs can also play a role in a woman’s risk for dense breasts and breast cancer. While there's much research that needs to be done, from my experience, there's a lot we can do already to potentially intervene and help women with dense breasts. As we wait for more definitive research, we can learn from the nutritional genomics and functional medicine realms. 

We have long known that pro-inflammatory conditions are underlying drivers for so many of the chronic diseases we see today, from cancer to heart disease, diabetes, autoimmune disease, depression and more. The flip side of inflammation is oxidative stress. They go hand in hand. Some of the genes that drive these processes are now also being linked to dense breasts and potentially the increased breast cancer risk that women with dense breasts have. 

My question is, why can't we use some of these dietary lifestyle and nutritional supplement interventions that we already know decrease many of these pro-inflammatory pathways? Why can't we start using those in clinical practice as we wait for research and clinical trials to better refine our knowledge?  The fact is, we can! But it takes education, awareness and advocacy to implement these strategies more widely and make a difference now.


Reference:

1) link to polygenic model – breast cancer, Lynch syndrome etc https://healthresourcedigest.blogspot.com/2022/03/the-future-in-personalized-medicine.html

2) Link to genetics/genomics https://modernhealing1.blogspot.com/2020/11/what-is-lynch-syndrome.html

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