Tuesday, April 30, 2024

UNDER THE LENS: LIVE BREAST CANCER CELLS IN DENSE BREAST TISSUE

 3/6 ‐ 3/8/2024 ‐Molloy University Labs, NY. Dr. Noelle Cutter works with live breast cancer cells in dense breast tissue (Adenocarcinoma, breast, epithelial  ER+ ‐estrogen receptor expressed).  

 This observational study explores the functional phenotypic differences that make dense breast tissue. Because it is  widely noted that women with dense breasts have a greater likelihood of developing cancer, understanding the  pathways and changes in gene expression may offer the first avenue for the enzymes enrolled and drug targets for  personalized medicine in pursuit of developing better treatment options.  

Day 1: Dr. Cutter is establishing the effectiveness of the tissue culture methods, indicating the capability of growing  the cells.  Working with epithelial cells that are growing at the expected density rate, she is able to start extracting  DNA, RNA and proteins. By running functional analysis, the study allows for the observation of cell reaction from  oxidative stress in the cell line. Additional information gathered include apoptosis (to monitor the cellular death) vs.  general growth rate to understand their growth properties.   

Day 2: Part of the functional analysis include the induction of environmental stress to provoke oxidative stress  response to record cell endurance within breast cancer cell lines. Over 36 trials showed response to oxidative stress  which could mimic inflammatory response from environmental stresses. Reports indicate continued cellular survival  and that “they're happy to keep growing… without any change in cellular deaths”.  Activating oxidative stress  included: physically adding stressors such as hydrogen peroxide, serum‐starving and glucose‐starving the cells‐ all  presenting the same response. 


Senescence in Dense Breast Tissue: A Functional Role for Metastasis
By: Noelle L. Cutter, PhD

Studies show that persistent populations of senescent cells can use senescence as an adaptive pathway to restart proliferation and become more aggressive. These are our dense breast cells. The blue ones are senescent cells.

Senescence, the state of irreversible growth arrest, has been proposed to play a role in the metastasis of dense breast tissue. Dense breast tissue is characterized by a higher proportion of glandular and connective tissue compared to fatty tissue. Studies suggest that dense breast tissue provides a conducive environment for cancer cells to thrive and metastasize.

One proposed mechanism involves senescent cells secreting factors that can promote tumor growth and metastasis. These factors include pro-inflammatory cytokines, growth factors, and extracellular matrix remodeling enzymes. Senescent cells can also alter the tissue microenvironment, making it more favorable for the survival and dissemination of cancer cells.

Additionally, senescent cells may escape the immune system's surveillance, allowing them to persist in the tissue and contribute to tumor progression. The accumulation of senescent cells in dense breast tissue over time may create a pro-tumorigenic milieu, facilitating the initiation and spread of cancer cells.



Furthermore, senescent cells have been implicated in promoting angiogenesis, the formation of new blood vessels, which is crucial for tumor growth and metastasis. By secreting angiogenic factors, senescent cells can stimulate the formation of blood vessels that supply nutrients and oxygen to the growing tumor, facilitating its expansion and dissemination to distant sites.

Overall, the proposed role of senescence in dense breast tissue metastasis involves creating a tumor-promoting microenvironment, facilitating immune evasion, and promoting angiogenesis, all of which contribute to the progression and spread of cancer cells. However, further research is needed to fully elucidate the mechanisms underlying this process and to explore potential therapeutic strategies targeting senescent cells in the context of breast cancer metastasis.


NOELLE CUTTER, PhD - Associate professor in higher education in biology and chemistry, lover of technology and learning. Motivational speaker focused on student success. Ironman athlete. Data enthusiast.  United with an expanding research team dedicated to collecting data on women with dense breasts and screening options for these patients, her initiative aims to investigate and gather conclusive information about dense breasts in specific groups- including age, body mass index, and amount of physical activity and the underlying diagnostics of breast cancer tumors. This research program is under a partnership with Molloy Univ. and Dr. Robert Bard, expert diagnostic cancer imaging specialist in NYC and other colleagues from the NY Cancer Resource Alliance.




Saturday, December 16, 2023

PATHOLOGICAL VIEWS OF DENSE BREAST TISSUE

Written by: Dr. Robert L. Bard  (12/2023)
Edited by: Carmen Regallo-Dewitt

Decades since the advent of breast scanning technology, innovations in non-invasive diagnostic imaging provide new options in the field of early detection.  A mammogram can show how dense your breasts are including how low or high in density. However, over-compression artificially lowers the radiographic density.



 [Image 1] in this standard mammogram, a dense breast is presented side by side. The white shaped “V” that comes down the top center are the pectoral muscles of the chest wall. On the far outside, the white line is the skin outline of the breast. This is the dermal tissue causing the white line viewed enface.  Radiologists always study this for any indication of inflammatory disease of the skin or inflammatory breast cancer, which manifests itself in skin thickening.  Between the center wedge and the skin outline, you will find homogeneous cloudy areas with patchy black spaces within as an example of dense breast tissue. 

Usually, dense breast tissue appears white on a mammogram. We must identify them as one of two forms of breast density; one is called FIBROCYSTIC or fibrous [Image 2] which is homogeneously white. Occasionally you can see a branching of blood vessels, dilated ducts or a streak of fat inside the dense breast tissue. This is the most common type of dense breast tissue and generally seen in the over 40 population.

[Image 3] Another example of a dense breast shows the difference between homogeneous white versus the whitish area. This is filled with dark, wormy looking structures, which are the breast glands called GLANDULAR tissue. This kind secretes milk and its glands are often dilated. Both Fibrous and Glandular may appear similar under a mammogram as highly dense areas, but they look completely different under an ultrasound scan.  

Through ultrasound, we can check for tumors easily through fibrotic dense breasts because it stands out as a black region (or a black hole) within the white area. As shown in Image 3, a black hole could get lost, making it more difficult to image this type of dense breast.  In this case, a solution is the use of elastography [Image 4], which offers visual confirmation as indicated by color data. Elastography can measure tissue density (its hardness or elasticity) within the glandular breast tissue. 

This tissue type is more common in the under-40 age group and is associated with other glandular proliferation such as endometriosis and is reportedly linked to dermal inflammation. In published reports, comparative studies between FIBROUS and GLANDULAR breast tissue studies remain limited.  We are observing (especially in the younger age groups) expanding reviews of these types of tissue density aligned with the rates of breast cancer to confirm the rate of malignancy in tissue alteration from normal.





Originally published in WOMEN'S HEALTH DIGEST

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





CONTRIBUTORS

ROBERT L. BARD, MD  (Diagnostic Imaging Specialist)
Having paved the way for the study of various cancers both clinically and academically, Dr. Robert Bard co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital Imaging technology has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. His most recent program is dedicated to the reporting of mental health diagnostic and innovative solutions including the use of modern neuromagnetic technologies and protocols in his MEDTECH REVIEWS program. 

ROBERTA KLINE, MD (Educational Dir. /Women's Diagnostic Group)
Dr. Kline is a board-certified ObGyn physician, Integrative Personalized Medicine expert, consultant, author, and educator whose mission is to change how we approach health and deliver healthcare. She helped to create the Integrative & Functional Medicine program for a family practice residency, has consulted with Sodexo to implement the first personalized nutrition menu for healthcare facilities, and serves as Education Director for several organizations including the Women’s Diagnostic Health Network, Mommies on a Mission. Learn more at https://bobbiklinemd.com 

MOVING THE BATTLE FORWARD: CANCER NEWS from the USPSTF

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