Sunday, September 24, 2023

Epigenetic Research Notes: Profiling the Dense Breast Paradigm (part 1)

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







2024 CLINICAL PROFILE OF THE DENSE BREAST PARADIGM - for the Obstetrics & Gynecology Society 
Written by: Roberta Kline, MD
Published by ICRS Medical Press Ltd.


Breast cancer affects the lives of hundreds of thousands of women every year and is a leading cause of death.  While we have made great progress in advancing earlier diagnosis and more individualized treatments, we still need to improve our approach to achieve our ultimate goal - prevention. This requires a deeper understanding of the molecular mechanisms and the multitude of factors that contribute to the development of breast cancer.  

Dr. Roberta Kline, recognized speaker and publishing crusader for women's health brings you a comprehensive review and a deep-dive analysis of the current research  findings about breast density and its major risk factors for breast cancer.  Her reports uncover current imaging practices and clinical protocols updated in great support of breast density detection and the means of addressing this growing condition that affects over 45% of the female population. "Knowing a woman has greater breast density is a critical first step, but it doesn’t end there... we need to go further by understanding the causes of breast density, and how they relate to breast cancer-- we now have another avenue to proactively intervene to reduce risk or even prevent breast cancer in the first place."  This textbook is a champion in targeting the Dense Breast Paradigm as a blueprint and a clear course study for all clinical professionals who are dedicated to women's early detection and prevention programs. (More information)



LAUNCHING IN 2024: NATIONAL COALITION OF WOMEN'S HEALTH SUPPORT
Professional health orgs, foundations and advocates of women's health disorders (primarily cancers) is uniting to form a national alliance of collaborators. This collective group is focused on "doing more together" as far as exploring new resources, sharing current ideas and addressing a wide range of topics about women's issues. Meetings like our latest Women's Powermeet series discussed the latest in diagnostic and therapeutic solutions while introducing who's who in national crusadership in the advocacy realm. Clinicians are also welcome to discuss patient-dedicated road maps and a more thoughtful health analysis and research-based evaluation. It is this level of commitment to women's health that provides a deeper sense of care for the patient that lends itself to a more holistic and integrative strategy to therapeutics. It is also this philosophy that draws more intuitive and insightful awareness on a global scale to offer collaboration platforms too better share insights on a patient's disorders to seek out better solutions. (See Women's Health Digest)





FOR IMMEDIATE RELEASE

PROCLAMATION: 9/27 Is World Dense Breast Tissue Day

9/19/2023- Mr. Joe Cappello, co-founder of the "Are You Dense?" Foundation was invited to attend the Santa Clara County Board of Supervisors meeting at County Government Center to receive an official proclamation by Santa Clara County Supervisor (and former California State Senator) JOE SIMITIAN, officially confirming September 27 as World Dense Breast Tissue Day.  According to Mr. Simitian, this proclamation was sparked by earlier discussions about the late Nancy Cappello who passed away of breast-cancer related complications from dense breast tissue.  "(Nancy's) own life experience... said others should have more power, more knowledge, more ability to affect the decision making in their own healthcare. For this, we are a better state, a better county, and in fact a better nation by virtue of her work."

To date, Joe Cappello continues to build and promote educational programs supporting research, clinical upgrades and improved scanning/monitoring programs.  The "Are You Dense?" Foundation and "Are You Dense?" Advocacy are produced by the Cappellos in pursuit of saving lives through awareness through uniting with community leaders, clinical professionals and public recognition off the continued risks of having dense breast tissue.

TRANSCRIPT OF PROCLAMATION: 9/19/2023

County of Santa Clara Board of Supervisors


SPEAKER: Santa Clara County (CA) Supervisor Joe Simitian- District 5

Thank you, Madam President. And I'm going to look to the clerk to see if we can bring Mr. Joe Cappello from “Are You Dense?” in Connecticut up on the screen. 

Colleagues and members of the public, you'll recall of course that just last week, we adjourned our meeting in memory of Nancy Cappello, who passed away almost five years ago now. And it provided an opportunity for our board to reflect on Nancy's extraordinary work over literally decades. We also took the opportunity at our last meeting to express our formal support for the Find It Early Act which is an effort at the national level congressional level to take the next step in terms of addressing the cancer risk of women with dense breast tissue. Today, we are calling out the formal acknowledgement of World Dense Breast Tissue Day. And the reason for that, Joe, and colleagues and members of the public is to ensure that we take advantage of this opportunity to identify September 27th as World Dense Breast Tissue Day, so that members of the public will have the information, the knowledge, the power that Nancy Cappello thought they were entitled to all those years ago.

And as we have discussed previously (so I won't speak at quite substantial length today) this is information that patients need to have. They are now entitled to have it by law.  That entitlement is in large measure, a function of the fact that Nancy Cappello took her own life experience and said others should have more power, more knowledge, more ability  to affect the decision making in their own healthcare. For this, we are a better state, a better county, and in fact a better nation by virtue of her work.  Joe, if you were here, I would have you up to the podium and I would hand you the physical commendation. But by virtue of our virtual connection today, I will virtually present it to you and we will send you the physical commendation and I hope it will find a place at “Are You Dense?”. 

I'm guessing that your screen-... It doesn't reveal it, but I am wearing on my lapel the “Are You Dense?” button which I wore all those years ago when I was privileged to work with Nancy and the organization on California law. With that, Madam President, I say thank you to our board, and to my colleagues for their support on this measure and through the chair. With your permission, I'd like to give Mr. Cappello an opportunity to say a brief word or two.


Guest Speaker: JOE CAPPELLO

Well, thank you, Supervisor Simitian. As I said before, it's a real pleasure. I finally got to meet the other Joe in Nancy's life. And believe me, she always had kind words to say about you, and you were always a standup guy. You were the one that she could count on for honesty and truthfulness when we were doing our legislative work in California.  What we have now is a disclosure law, which is a national law, which will take effect a year from now.  This is huge step for the health of women all over this nation. What it's going to do is standardize (diagnostic care) in the medical field for women with dense breasts. I thank you in the name of Nancy for the proclamation. She deserves it all. She worked hard and worked smart. She was not only prettier than me, <laugh>, but smarter than me. And, I thank you on her behalf. I appreciate that. Thank you.

The Board of Supervisors of the County of Santa Clara, CA regularly meets in the Board of Supervisors’ Chambers, County Government Center, 70 West Hedding Street, San Jose. Regular meetings are held on designated Tuesdays at 9:30 a.m. The Board also holds regular meetings for the purpose of adjourning into Closed Session on Mondays at 2:00 p.m., which may be combined with meetings scheduled for the presentation of ceremonial items to be heard at 4:00 p.m.









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