Saturday, September 22, 2018

CANCER 101: The Essentials of How Cancer Happens (and Doesn't)

CANCER MADE EASY: GENETICS & MUTATIONS
By Dr. Patricia Clark

Our DNA and our genetic material is breaking and being damaged every single day. That's just the wear and tear of life. Our bodies have genes and mechanisms to repair broken DNA, and our immune systems have mechanisms to identify and destroy cancerous cells. With breast cancer, 5% to 10% of people have a genetic predisposition that raises their risk of development of breast cancer.

If we have a cell that can't be repaired, our immune system can recognize it and our natural killer cells can destroy it. So that's how things ought to work. Eventually, you accumulate MUTATIONS over a lifetime as more genes and genetic information are damaged and break down. Somebody like Angelina Jolie had a gene that predisposed her to get breast cancer. She had a gene called BRCA which is a DNA repair mechanism gene. She had one copy of that gene that did not work causing an 87% chance she was going to get breast cancer. She decided with a risk this high for the particular genetic mutation she had, she was going to get mastectomies and remove her ovaries, which were also at risk.

Genes are like a paragraph of instructions that tell a cell what it is supposed to do, such as what proteins it should make. If all the letters in the instructions are in the correct order, or the gene is “spelled’ correctly, the gene can be read by the cell and everything works. Pathologic mutations in genes have to occur in very specific locations for a cell to no longer be able to understand the instructions it carries. We have all read paragraphs where letters or words are left out, but we can understand the meaning of the paragraph. 

Changing the letters at a key location though, can change the entire meaning of the paragraph of instructions. For instance, If I have a sentence in that paragraph with the word CAR, and I change that "R" to a "T" it now reads CAT. That might change the entire meaning of the message to the cell, and it will no longer be able to carry out it’s functions. That would be a pathological mutation and raise the risk of inheriting cancer or of a cell becoming cancerous.  Had I changed the C to a K, and made the word 'KAR', the cell may have still been able to read and understood the word carrying that mutation and can happily continue making the proteins it was supposed to manufacture. This is why some mutations may cause no harm to the cell as long as the cell can still read and understand it’s instructions while other mutations can stop a gene in its tracks, being rendered pathologic. 

This is the simplest way to describe mutations.

A lot of mutations aren't going to matter. You have to mutate them in very specific spots before a cell cant read it. To get a cancer, it's not enough to have one mutation. You have to have one or more specific mutations to enable cells to divide uncontrollably. Then you've got to have a mutation that allows it to get out of the organ that it's in (such as a milk duct) and escape into the nearby adjacent tissues, forming a tumor. That's a whole other gene that has to be bad. You have to have a gene in there that allows those cells to bring in their own blood supply so they can keep the tumor fed and alive.. So that's yet another genetic mutation.

Like with breast cancer, people don’t die of the breast cancer in their breast. They die if it traveled into their entered their bloodstream and lodged in their lungs, it lodged in their liver, it lodged in their bones it lodged in their brain... if it had the mutations it needed to escape the breast and lodge in an organ system that you need. In order to do that it that takes a whole other set of genetic mutations. We can test the tumors for these mutations.  Putting a garden variety breast cancer cell in the lung (per se), may be sort of like putting a Palm tree in Alberta, Canada. You can put a Palm tree up there, unless it has a set of very specific genetic mutations, it's not going to survive the winter up there.

“IT’S NOT THAT EASY TO GET CANCER”:
So that's why all of us aren't running around with cancers. 1 in 8 women will develop breast cancer over their lifetimes. We have genetic mutations that we accumulate, a lot of them meaningless. Then the other thing is you've got to have the exact right mutations all lined up in a row for something to become cancerous. For the same reason not all firefighters in 9/11 die of cancer, it also depends on genetic predisposition and a person’s ability to protect from and heal environmental insults.  We see families where it seems everybody's getting cancer but we can't find a nice single smoking gun or a silver bullet that “caused” it. If cancer were a single process or silver bullet, we’d have it cured already. We're going to have cancer forever because you can't stop the body from mutating or accumulating genetic damage. If you could, we would all be immortal.

So that's the briefest of the basics. Understanding cancer from the angle of genetic mutation and  predisposition helps you see why some people get it, some people don't. Some people may not have the robust repair mechanisms or the lifestyle to fight it off.  Many are sedentary-- they don't exercise, they drink alcohol, or have other lifestyle risks that are another part of it. 

There are also a lot of environmental factors that can turn genes on and turn genes off. That’s a whole other layer. You can be predisposed because you carry a unique malfunctioning gene ... which carries a variable increase in somebody's risk.  They may have a 40% risk they're going to get cancer- or you can see it as that there's 60% risk they never will. We have proto-oncogenes that must be turned on to cause a tumor to form, and tumor suppressor genes that must be turned off to allow a cancer to form. We may or may not be exposed to the environment inside or outside the body that's going to turn it on - or off.



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ABOUT THE AUTHOR:
Awareness for a Cure welcomes our newest cancer expert, Dr. Patricia Clark- Breast and Oncoplastic Surgeon. Dr. Clark is a renowned speaker at the BC3 (National Breast Cancer Conferences) and is currently the medical director and surgical oncologist at the Ironwood Breast Cancer and Research Centers in Scottsdale, AZ. You can learn more about Dr. Clark at: www.drclarkmd.com


Eliminating Cancer is not enough:
A woman’s function and body image matter. For most women, there is no survival advantage to mastectomy. By using oncoplastic techniques such as breast reduction or mastopexy at the time of lumpectomy, selected women with larger tumors or more complex disease can now have complete removal of their cancer and still have a good cosmetic result. While Dr Clark personally performs oncoplastic procedures, high quality plastic surgery consultation is available for all women requiring reconstruction from mastectomy, and to optimize outcomes in selected women undergoing oncoplastic procedures.  Surgery can be performed on the other breast to provide symmetry. We don’t want the breast to be a reminder of cancer in years to come. www.drclarkmd.com


Disclaimer & Copyright Notice: The materials provided on this website/web-based article are copyrighted and the intellectual property of the publishers/producers (The NY Cancer Resource Alliance/IntermediaWorx inc. and Bard Diagnostic Research & Educational Programs). It is provided publicly strictly for informational purposes within non-commercial use and not for purposes of resale, distribution, public display or performance. Unless otherwise indicated on this web based page, sharing, re-posting, re-publishing of this work is strictly prohibited without due permission from the publishers.  Also, certain content may be licensed from third-parties. The licenses for some of this Content may contain additional terms. When such Content licenses contain additional terms, we will make these terms available to you on those pages (which his incorporated herein by reference).The publishers/producers of this site and its contents such as videos, graphics, text, and other materials published are not intended to be a substitute for professional medical advice, diagnosis, or treatment. For any questions you may have regarding a medical condition, please always seek the advice of your physician or a qualified health provider. Do not postpone or disregard any professional medical advice over something you may have seen or read on this website. If you think you may have a medical emergency, call your doctor or 9-1-1 immediately.  This website does not support, endorse or recommend any specific products, tests, physicians, procedures, treatment opinions or other information that may be mentioned on this site. Referencing any content or information seen or published in this website or shared by other visitors of this website is solely at your own risk. The publishers/producers of this Internet web site reserves the right, at its sole discretion, to modify, disable access to, or discontinue, temporarily or permanently, all or any part of this Internet web site or any information contained thereon without liability or notice to you.

Monday, September 10, 2018

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): "Where we are, and aren’t"

By: Constantine Kaniklidis Medical Research (Cancer Knowledge network) & Director of No Surrender Breast Cancer Foundation (NSBCF)-- circa 2018, September

SEE BIA-ALCL FEATURE @ NEWS1
Here some reflections, and a plea for further, more systematized and coordinated action and consensus:

First, the just published LYSA Registry data from the French Cancer Agency [reported at ASCO 2018] has shed some further light on two prognostically distinct classes of BIA-ALCLs (based on effusion, breast tumor mass, and lymph node involvement), with in situ BIA-ALCLs exhibiting an indolent clinical course that enables complete remission typically after implant removal, in contrast to infiltrative BIA-ALCLs exhibiting a more aggressive clinical course, with in fact a prognosis virtually identical to systemic anaplastic large cell lymphoma (ALCL), despite real differences. Further clarification was provided in AU-NZ studies [especially Loch-Wilkinson, Plast Reconstr Surg. 2017 Oct], higher-surface-area (HAS) textured implants significantly increased the risk of BIA-ALCL (over 14 times higher with Biocell textured implants and almost 11 times higher with polyurethane (Silimed) textured implants compared with Siltex textured implants, so there clearly is a risk hierarchy at play here.

Second, being mindful of overtreatment (always a concern), nonetheless given that BIA-ALCL related death, although rare, is predominantly due to uncontrolled local disease progression, there is a role in patients with more advanced local disease – particularly in the minority of patients whose disease extends beyond the capsule – for chemotherapeutic intervention, and at this time the best evidenced first-line therapy apart from the strongly toxic CHOP family of regimens is the monoclonal antibody brentuximab vedotin (Adcetris) based on its role in refractory in ALCL, despite the limited but still positive data of its off-label use in BIA-ALCL; and I have seen some cases of patients progressing on CHOP therapy but achieving pathological complete response (pCR) with brentuximab vedotin in the second line. Given its comparatively favorable side effect profile and higher tolerability over traditional chemotherapies, it retains some considerable appeal.

Third, for myself, given that:
(1) the NF-kB) pathway is commonly deregulated in lymphomas, and that
(2) curcumin can inhibit growth of these cell lines and increase their chemosensitivity to cisplatin, and given also that
(3) it (curcumin) increases apoptosis and differentiation of vitamin D-treated tumor cells, with direct binding of curcumin to the vitamin D receptor (VDR), and that
(4) curcumin modulates the well-known overexpression of EZH2 in anaplastic lymphomas and can down-regulate the  JAK/STAT pathway that is also incriminated in BIA-ALCL, then I have (strictly ad hoc-ly and off-label) counseled the deployment, with provisional but promising success, of a regimen of high-penetrance curcuminoids (either phytosomal or nanoparticulate) and optimal-dosed Vitamin D3 (achieving 25(OH)D assay levels of at least 66 ng/ml and above), in the small number of BIA-ALCL cases I have consulted on, but clearly this requires validation in clinical trial. And Mark Clemens' recent findings suggesting that some BIA-ALCL are associated with a chronic allergic immune response to currently undetermined antigen(s) - with IL-13 activity (associated with allergic inflammation) as well as eosinophils and mast cells surrounding the BIA-ALCL tumors plus the presence of IgE – is tantalizing in this connection of anti-inflammatory interventions.

Going Forward, Work Still To Do:
1.     I am also looking to press for the expansion of the European Commission Medical Device Expert Group (VMDEC) Task Force with respect to collection and analysis of EU-based BIA-ALCL cases, but VMDEC registry data must be coordinated with other non-EU entities – like the PROFILE Registry maintained by the The Plastic Surgery Foundation here in the States, the Australian Breast Device Registry,  among many others – if we are to establish a larger and more comprehensive cross-boundary collaborative BIA-ALCL surveillance initiatives to advance our knowledge and better serve the many women affected (and often overlooked and sometimes misdiagnosed as Hodgkin lymphoma or other entities).

2.     It is disconcerting that we still, even in 2018, lack consistent standardization and reporting regarding pathological examination of mammary implants (most institutions often continue to recommend gross examination alone).

3.     Furthermore, we are not doing enough to educate patients and their health professionals on the importance of routine surveillance after implantation.

4.     And we must finally – long overdue -bring explicit consent issues to the fore to assure fairness to patients. It would appear that most breast-focused plastic surgeons in the U.S. and the UK fail to consistently include risk of BIA-ALCL and that uniform informed-consent documents lack widespread adoption and use, so a model BIA-ALCL informed consent is required and effective efforts made to assure that the patient is not simply “allowed” to read and decipher the information as it is found in the informed consent agreement as is all too commonly the case, but that health professionals first openly and candidly discuss not only the risk of BIA-ALCL but also the common presenting symptoms (a mass, breast swelling/pain, or delayed-presentation seroma / effusion) of BIA-ALCL the patient should be on guard for which would trigger a mandated evaluation. I call this the need for “informed discussion” in addition to mere “informed consent”, and that need was best put by the UK High Court (Judgement in Montgomery ‘v’ Lanarkshire Health Board) that stated that “risk shouldn't be a numbers game, it should be part of dialogue”.

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Constantine Kaniklidis of evidencewatch.com
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Oncology Reviewer, Current Oncology
Member, Society for Integrative Oncology (SIO)
European Association for Cancer Research (EACR)


Disclaimer & Copyright Notice: The materials provided on this website/web-based article are copyrighted and the intellectual property of the publishers/producers (The NY Cancer Resource Alliance/IntermediaWorx inc. and Bard Diagnostic Research & Educational Programs). It is provided publicly strictly for informational purposes within non-commercial use and not for purposes of resale, distribution, public display or performance. Unless otherwise indicated on this web based page, sharing, re-posting, re-publishing of this work is strictly prohibited without due permission from the publishers.  Also, certain content may be licensed from third-parties. The licenses for some of this Content may contain additional terms. When such Content licenses contain additional terms, we will make these terms available to you on those pages (which his incorporated herein by reference).The publishers/producers of this site and its contents such as videos, graphics, text, and other materials published are not intended to be a substitute for professional medical advice, diagnosis, or treatment. For any questions you may have regarding a medical condition, please always seek the advice of your physician or a qualified health provider. Do not postpone or disregard any professional medical advice over something you may have seen or read on this website. If you think you may have a medical emergency, call your doctor or 9-1-1 immediately.  This website does not support, endorse or recommend any specific products, tests, physicians, procedures, treatment opinions or other information that may be mentioned on this site. Referencing any content or information seen or published in this website or shared by other visitors of this website is solely at your own risk. The publishers/producers of this Internet web site reserves the right, at its sole discretion, to modify, disable access to, or discontinue, temporarily or permanently, all or any part of this Internet web site or any information contained thereon without liability or notice to you.

Video Part 1: Introduction & Spotlight on Nancy (Natl Dense Breast Disclosure Act)

Natl Dense Breast Disclosure Law (9/10/2024) Video Part 1