SelectScience® Cancer Research Summit is celebrating its third year, bringing together the scientific community and pioneering manufacturers to foster collaboration and facilitate the dissemination of crucial updates in cancer research. Each year, scientific presentations by expert speakers deliver the latest findings in their respective topics, offering practical skills through engaging technology showcases, interactive resources by industry leaders- helping the community to harness the power of networking to drive impactful collaborations.
For the second year in a row, ICRS top clinical advocate Dr. Noelle Cutter was elected to be one of the headliners of this global (virtual) medical event. With her, she brought fellow cancer researchers and two powerhouse publishers in women's health- Dr. Robert L. Bard (Sr. Cancer Imaging Radiologist) and Dr. Roberta Kline (OBGYN/ Genomics Expert). Together, Dr. Cutter's presentation promises to empower the medical community with the most comprehensive report on "Molecular Changes in Dense Breast Tissue" and its metabolic correlation with Breast Cancer.
This video presentation is comprised of 3 presentations which can be accessed in full assembly or as separate clips: (1) Dr. Noelle Cutter -part 1 (2) Dr. Robert Bard (3) Dr. Roberta Kline (4) Dr. Noelle Cutter - Part 2. Scroll below for direct access to all presentations and transcripts.
Breast cancer is the most common cancer worldwide, recently surpassing lung cancer in 2020. Globally, it is the number one cancer in both developed and underdeveloped countries and affects more than 2.3 million people, both men and women worldwide, despite its global abundance. Knowledge about the first steps in tumor initiation is important for early detection. However, the exact mechanisms of tumor initiation are still unknown. The median age of diagnostics is 62 to 63 years old, but more recent data also shows that breast cancer is the most common type of cancer among young women.
The first question people ask when there's a cancer diagnosis is "how do we treat it?" As you can see from the 109th annual meeting in Boston, we can find cancer of the breast and treat it with image guidance using ultrasound and MRI with focal therapies. Dr. Barens is now the current chair of research for the Tuck University in the Netherlands. So (enclosed) we see the cancer, it's dark on the ultrasound and it's vascular. We can mention the tumor vascularity and also with the the scan we see it's already metastasized. So we do everything staging with non-invasive imaging, non-bio, back to biopsy. Where do you biopsy? (Enclosed) is the mass. You put it here and get a good biopsy report or do you put it here and said that you, you got dead cells? Repeat the biopsy. So there are false positives, not only with biopsies and false negatives with biopsies, there are false positives.
Now this looks like a dense breast, but it isn't. This looks like a not dense breast, but it is because (enclosed is) the cancer. It's a huge six millimeter cancer on the outside of the breast and what does it look like with ultrasound? So is this a rash, a red breast? No, this is the epidermis again, and this is a five millimeter to six millimeter epidermal lymphatic cancer. Rare it's an inflammatory breast cancer rare, but this is the best way to find it. And sometimes the only way, again is an inflammatory cancer or a allergic reaction. Again, sonogram is 5.2 millimeters depth, which should be 1.2 with the allergen. And since the nipple and skin can be involved, we also use optical systems that see the microanatomy and see if the tumor has invaded the nipple tissue or the skin. How do we find that? Well, with looking at the skin, this is a intradermal white area.
It's a plaque, and the 4D scan shows multiple plaques. So this is uranium toxin, which is in the skin. You can find it and measure it. Let me leave you with the world conference showing that angiogenesis and vascularity are the key to finding cancer progression and seeing if the validated anti-cancer treatment works. (Enclosed is) something common. This is a reactive lymph node from from COVID. This is a metastatic lymph node. Notice the difference tumor vessels on the outside penetrating, and this is benign inflammatory vessels. (Enclosed is) a mass under the arm and a patient receiving biologics. So they thought it was a fatty tumor. No, it's a lymphoma. And notice this is connected with a vascular pedicle to the big subclavian artery. So you put a needle in (enclosed is) and it bleeds. This was courtesy from one of the heads of the ultrasound society in Europe. Notice the right side. This white line and blue line show that it's it's soft tissue area and on the left side the white line is thicker, thicker and now it's red, which shows that it's inflammatory tissue. So this is a case of benign fasciitis, which was treated with steroids instead of a metastatic tumor. So basically this is what the world is doing and we can be doing it by adopting all the new imaging technologies.
I'm Dr. Roberta Kline. I'll be discussing the role of epigenetics. Gene expression is the final result of many systems interacting with each other. Now while alterations in DNA such as genetic SNPs and mutations are the best study, epigenetic changes are emerging as very important regulators, and both of these interact with the exosome or the sum total of all environmental exposures over a person's lifetime. These interactions are multi-directional. The exosome influences epigenetic changes. DNA affects how we respond to the exosome as well as our ability to create these epigenetic changes. And then the resulting genetic expression provides yet another feedback loop to influence all of these systems. Epigenetics literally means above the genome and it's our body's way of adapting to environmental cues without changing the actual DNA code. There are three main ways in which this occurs. There's methylation of DNA modification of histones, and then non-coding RNA.
Resistance to chemotherapy is also a huge concern and a hot topic of research that is now pointing to epigenetics as a potential solution. There are multiple clinical trials ongoing in various phases looking at intervention with some of these epigenetic agents. Most of these are focusing on two main enzymes, the methyl transferases, and another key epigenetic mechanism that involves enzymes called histone diacetyl asis. Nutritional epigenetics offers application of nutritional strategies including the use of specific phytonutrients that can modulate these epigenetic mechanism. Here on the left, you can see a list of various phytochemicals and how they interact with different epigenetic mechanisms or cancers including breast cancer. And on the right you can see this pictorially in terms of how they're acting with the epigene. Now these strategies are ones we can use today as part of a comprehensive personalized approach for the prevention and the treatment of elevated breast density and breast cancer.
Molecular profiling of gene expression of breast cancers has demonstrated that tumors are remarkably heterogeneous. More recently, molecular analysis of the microenvironment has demonstrated similar heterogeneity, but the epidemiological clinical and pathological correlations of this variation are not well studied. Recent advances of breast cancers and the surrounding and microenvironment have revealed important stromal and epithelial interaction and have led to the speculation that the microenvironment may actually be dominant over tumor biology, especially early in the stage of progression when invasive cancer cells are still forming.
We used a subset of genes quantified by the cancer genome atlas, which represent copy number variation where the CNV is low and downregulation of gene expression is seen, or we can look at copy number variations and gene upregulation for our functional genomic study. We next correlated this data to methylation changes across the genome using a platform known as MoMA, which is a methylation detection array. The image presented represents a sample representation of the heat met, which included 749 differentially methylated probes showing the segregation of mammographically dense and non mammographically dense patients with breast cancer. Since this analysis is based on the comparison of the two co cohorts of mammographically dense and non mammographically dense, there are regions that are found more frequently methylated in mammographically dense or non mammographically dense, breaking down to approximately 60% methylated in mammographically dense and 40% methylated in non mammographically dense tumors. For these regions that differentiate between the mammographically dense and non mammographically dense, we next determine which methylation event potentially represses transcription.
When we analyze our subset of genes identified by the cancer genome atlas and shared publicly that are differentially expressed in patients with breast cancer and high mammographic density, we then uploaded our methylation gene list to a bioinformatic platform known as David to help identify any enriched themes in um, biological functionality for the subset of our genes. The David platform is the database for annotation visualization and integrated discovery and provides a comprehensive set of functional annotation tools for investigators to understand the biological meaning behind some of the large gene lists, such as the one that we isolated for our mammographically dense and our non mammographically dense patients. The star on the slide indicates pathways that are currently under validation in our lab and the hashtag indicates publications that have already been accepted for our gene analysis. That list.
Our studies have shown that gene expression upregulation of these two key genes, ZB one and TNF Alpha, also induced functional changes in our cell lines, which include cellular proliferation and invasion. Being that TNF alpha and ZB one promote cell displacement and invasive myth through that EMT pathway, we hear and propose that these genes employ a pathogenic mechanism to render mammographically dense cells to metastasize. EMT is an overly complex but also reversible event. Therefore, further investigation into these genes in the an inhibition of either TNF alpha or Zev one might be an effective strategy for personalized medicine and cancer therapy.
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