marijen, I read this article in the WSJ yesterday, and just read again the comments from readers.

It's disheartening, in so many ways.

The family involved seems to have not understood that genetic information is ever-changing - this should have been clearly explained to them by a genetic counsellor, as it was explained to me 14 years ago.

The articles notes "There are tens of thousands of BRCA variants and new research reveals that not all confer the same level of risk to a patient. Some gene variants “have intermediate or moderate levels of risk, not full-blown risk," says Fergus J. Couch, a professor at the Mayo Clinic, whose lab has worked on some of these studies.". Seriously, this is being presented as new news? I knew this from my own reading 14 years ago prior to my discussions with the genetic counsellor, and this was confirmed in that discussion. Anything I've read that mentions risk levels associated with the BRCA1 and BRCA2 mutations always presents a range of risk, never a single number.

The way the family feels now, and the way the story has been presented, indicates that some or all of the women regret their decisions to have prophylactic surgeries, based on the new information about their BRCA mutation. Well, what about the fact that they still have the family history of cancer? That hasn't changed. And it's not well explained that the new VUS status for their particular BRCA mutation does not mean that this mutation might not in fact present a high risk - VUS means that maybe it will or maybe it won't, and we just don't know yet. That's covered off in the article in one short sentence that's easy to miss. I appreciate that the family members are angry because they had these surgeries thinking their risk was much higher - but they are still high risk. And with their family representing such a large percent of the people with this mutation, and with so many of them having had prophylactic surgeries, at this point it may be very difficult to ever truly know what their risk really was.

It's mentioned in the article, but not emphasized, that changing the assessment of a genetic mutation from high risk to VUS status happens to only 1% of genetic mutations. So this cautionary tale about a very rare situation will scare some people away from genetic testing; not knowing their positive status and taking preventative action might lead to some deaths from cancers that could have been averted.

Then there are the letters. So little understanding of why people get genetic testing and why those who test positive for a high risk mutation often choose prophylactic surgery. No understanding that screening can miss some breast cancers and that even with extensive monitoring, sometimes breast cancers are not found when they are early stage, or that sometimes early stage breast cancer kills. One writer mentioned a 100% survival rate for breast cancer caught early and no one has contradicted her and provided the facts. A few people, all personally affected, have mentioned that there is no effective way to screen for ovarian cancer and that most ovarian cancers are found at Stage III or IV, but no one unaffected seemed to have any idea about this. One man mentioned that he is BRCA positive and has had breast cancer but every other writer seems to think this is a female issue.

I know how poorly educated the general public is about the realities of breast cancer so the fact that they are even more ignorant about genetic testing and the implications of being positive shouldn't surprise me, but it is demoralizing.

New Standard Likely for Some Metastatic HER2 Breast Cancer

CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative Breast Cancer Trials

CytoDyn... a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today continued promising clinical responses from its metastatic triple-negative breast (mTNBC) Phase1b/2 trial and its trial investigating leronlimab for the treatment of metastatic breast cancer (MBC).

"In the first patient, we're encouraged to see that after 11 weeks these additional data provide further preliminary evidence of efficacy, as demonstrated by sustained undetectable levels of CTCs and a reduction of cancer-associated macrophage like cells (CAMLs)," said Bruce Patterson, M.D., Chief Executive Officer of IncellDx...

CytoDyn's second patient enrolled is a stage 4 MBC patient. The metastasis progressed to the liver, lung and brain... This patient received her first injection of leronlimab on November 25, with one 700 mg dose each week... "The results from two subsequent scans of the metastatic lesions for this second patient demonstrated shrinkage of the tumors at both timepoints following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors."

The U.S. Food and Drug Administration (FDA) has granted a "Fast Track" designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH...

In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98 percent in a murine xenograft model. CytoDyn is therefore conducting a Phase 2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.

http://www.globenewswire.com/news-release/2019/12/23/1963963/0/en/CytoDyn-Reports-Early-But-Strong-Positive-Clinical-Responses-for-Two-Patients-One-in-Metastatic-Breast-Cancer-and-One-in-Metastatic-Triple-Negative-Breast-Cancer-Trials.html

Olma, your easier to read link didn't work, but when I cut & pasted the words in your link to a search bar, I got the article.

Thanks!

Nanoparticle therapeutic restores tumor suppressor [p53], sensitizes cancer cells to treatment [research not on bc but bc is often p53-deficient]

Investigators have long sought a way to restore the activity of tumor suppressor genes such as p53. Most recently, attention has turned to an approach developed at Brigham and Women's Hospital that uses nanotechnology to deliver synthetic messenger RNA (mRNA). Leveraging advancements in nanotechnology, investigators from the Brigham have found that restoring p53 not only delays the growth of p53-deficient liver and lung cancer cells but may also make tumors more vulnerable to cancer drugs known as mTOR inhibitors. The team's findings are published in Science Translational Medicine...

Shi and colleagues, including co-corresponding authors Omid Farokhzad, MD, MBA, (director of Brigham's Center for Nanomedicine) and Wei Tao, Ph.D., (faculty in the Center), and first author Na Kong, MD, used a redox-responsive nanoparticle platform to deliver p53-encoding synthetic mRNA. The synthetic p53 caused cell cycle arrest, cell death and delayed the growth of liver cancer cells and lung cancer cells in which p53 had been depleted. In addition, synthetic p53 made the cells more sensitive to everolimus, a drug which is an mTOR inhibitor. The team reports successful results in multiple in vitro and in vivo models...

The authors note that further preclinical development and evaluation will be needed to explore that translational potential and scalability of the approach as well as its applicability to other p53 mutations and other cancers.

"We expect that this mRNA nanoparticle approach could be applied to many other tumor suppressors and rationally combined with other therapeutic modalities for effective combinatorial cancer treatment," the authors write.

https://medicalxpress.com/news/2019-12-nanoparticle-therapeutic-tumor-suppressor-sensitizes.html

Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Uganda and Cameroon Women

Babatunde Adedokun, Yonglan Zheng, Paul Ndom, Antony Gakwaya, Timothy Makumbi, Alicia Y Zhou, Toshio F Yoshimatsu, Alex Rodriguez, Ravi K Madduri, Ian T Foster, Aminah Sallam, Olufunmilayo I Olopade and Dezheng Huo

Cancer Epidemiol Biomarkers Prev; Published OnlineFirst December 23, 2019; doi:10.1158/1055-9965.EPI-19-0506

http://cebp.aacrjournals.org/content/early/2019/12/21/1055-9965.EPI-19-0506.abstract

thanks for the comment Santa B. That article scares the crap out of me b/c I took a multivitamin - as per my MO during chemo. The percentages seem Bonkers!

Lumpie I thought the same thing...

In my country, we are told to run from B12 during treatment. Really, everybody in our support FB group knows to avoid it. Interestingly, I joined a German FB group (not my country, but I speak German) and people were recommending to take B12. That suprised me, as you can imagine.

I was thinking the same as some of you say above. Maybe the defficiency is the problem, B12 is often taken by vegans...

When I was first diagnosed, I found a study of men, lung cancer and B12 online . The men who had taken high doses of B12 daily before diagnosis had a higher incidence of lung cancer. That article alone convinced me avoid B12 supplements and I had been using B12 for years on and off because I tend to be anemic (congenitally low hemoglobin so iron supplementation does not help).

After chemo, I found a B complex in CVS that had no more than 100% of RDA of each vitamin. I took that for awhile but now have stopped.

'Are you kidding me?': Check out the price tags on 'combination drugs'
"It's an abuse of the system," said one critic. The "business model ... involves gouging insurers and health plans, which ultimately costs consumers."

Read in NBC News: https://apple.news/AfVtvQkE-S6ilLEYIBkKJ-w


Shared from Apple News