Chit, not happy. The connection was made several years ago. This is an article on the TNBC web page. Anyone reading this hear of this before?

https://www.tnbcfoundation.org/tnbcnews-betablockers/

Beta Blockers May Provide Breast Cancer Benefits

Date of publication: August 3, 2013

Beta blockers-drugs used to manage high blood pressure and certain other conditions-may be linked with improved prognosis among postmenopausal women with early-stage triple-negative breast cancer. These results were published in Breast Cancer Research and Treatment.

Observational studies have suggested that drugs known as beta blockers may reduce the likelihood of developing certain types of cancer, and may also be linked with improved prognosis after cancer develops.

To explore the relationship between beta blockers and cancer outcomes among women with triple-negative breast cancer, researchers in Italy conducted a study among 800 postmenopausal women who had undergone surgery for early-stage triple-negative breast cancer. At the time of cancer diagnosis, 9.3% of the women were using a beta blocker.

• A breast cancer recurrence or death due to breast cancer occurred in 14% of women who used beta blockers and 28% of women who did not use beta blockers. The better prognosis among women who used beta blockers was not explained by factors such as age, tumor stage, cancer treatment, peritumoral vascular invasion, or use of other antihypertensive drugs, antithrombotics, or statins.

This study suggests that beta blockers may improve prognosis among postmenopausal women with early-stage triple-negative breast cancer. But because this study was observational (and not a randomized clinical trial), it does not prove that beta blockers affect cancer outcomes. The researchers attempted to account for the many ways in which women on beta blockers could differ from other women, but it remains possible that some characteristic other than beta blocker use explains the better prognosis among women those women. Additional research on the effects of beta blockers is warranted.

Deleted, but box reserved for future use

Well, again not happy. Started in on researching info for a friend with a recurrence of TNBC. She goes to MD Anderson. She likely will take this back and the other articles too and ask why they weren't aware of this.

https://www.mdanderson.org/publications/conquest/summer-2014/betting-on-beta-blockers.html

Summer 2014 : Links to cancer

Betting on beta-blockers

BY Scott Merville

Tracking down the molecular details of how stress accelerates tumor growth and progression is pointing to a potential new role for a class of drugs used to treat cardiovascular disease and related conditions.

Years of research by Anil Sood, M.D., professor in Gynecologic Medical Oncology and Cancer Biology, show that stress hormones fuel progression of ovarian and other cancers, and that beta-blockers might be a new way to stifle that effect.

"Beta-blockers treat a variety of conditions, such as heart disease, high blood pressure, glaucoma and migraines, targeting a receptor protein in heart muscle that causes the heart to beat harder and faster when activated by stress hormones," Sood says. "Our research has shown that the same activation helps ovarian cancer progress and spread, so these drugs might have a new role for cancer."

Sood's findings include:

• When mice with ovarian cancer are stressed, their tumors grow and spread more quickly, but the effect can be blocked by the beta-blocker propranolol.
• Chronic stress triggers a chain of molecular events that protects breakaway ovarian cancer cells from automatic destruction. Heightened levels of the fight-or-flight hormones epinephrine and norepinephrine permit malignant cells to safely leave the primary tumor — a necessary step in cancer metastasis and progression — and avoid a cell-death mechanism called anoikis.
• When norepinephrine hits its target — the beta-adrenergic (ADRB) receptor — on tumor cells, it activates Src, a master regulator of cancer cell survival proteins, through another protein called PKA. Stress-activated Src is like a dam opening, only the flood is a chain reaction inside cells that promotes cell survival, mobility, invasion of neighboring tissue and creation of new blood vessels to supply
  the tumor.

Beta-blockers plug the ADRB receptor, blocking activation by norepinephrine and other hormones. Norepinephrine is the most abundant stress hormone found in ovaries.

Sood and colleagues analyzed data on outcomes of cancer patients treated with beta-blocker drugs from the Food and Drug Administration Adverse Event Reporting System. They found that mortality in patients treated with a beta-blocker fell by an average of 17% across all major cancer types, with a nearly 15% decrease in mortality among patients with ovarian and cervical cancers.

Sood continues to study biological mechanisms that may be affected by stress with the aim of identifying cancer patients who are most likely to benefit from beta-blockers and other stress interventions.

Magic glad you found it

Sewing , Timilol is a pure beta 2, Should do the job. But it's only perscribed for glaucoma. It's poplulation group would be small. My goal today is take a look at the studies Falls posted to determine what drug and dose they used in the studies as that wasn't stated in the articles. I'm going out on a limb with a guess. Metoporol 25 mg. b/c it's the oldest compared to prorpranilol/Inderal. Inderal wasn't well tolerated, metoprorol is very well tolerated. It is the number 1 used drug for BP in the world. But metoporol has both bet1 and beta2. We will see. BBL.

Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines
http://www.spandidos-publications.com/ijo/21/1/153
(Cakir, 2002)

Sassy: Older study, Used Isuprel/isoproterenol. Isuprel is a beta agonist. It mimics the sympathetic system. This study became the basis for Isuprel's use in the mouse studies. Isuprel /isoproteronol is NOT a blocker. Value of this study was for future studies. Nothing for our use right now.

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The sympathetic nervous system induces a metastatic switch in primary breast cancer.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940980/
(Sloan, 2010)

Sassy: Mouse study and other animals. Used propranolol as the beta blocker. Finding " treatment of stressed animals with the beta-antagonist propranolol reversed stress-induced macrophage infiltration and inhibited tumor spread to distant tissues" Translation: a beta blocker inhibited mets in mice and other animals in this study. Value of this study is for future research.

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Carvedilol suppresses migration and invasion of malignant breast cells by inactivating Src involving cAMP/PKA and PKCδ signaling pathway.
http://www.ncbi.nlm.nih.gov/pubmed/25579542
(Dezong, 2014)

sassy: Test tube study. CAR(carvedilol) was an anti-metastatic agent, which targets Src involving cAMP/PKA or PKCδ pathway in malignant breast cells.

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A Nervous Tumor Microenvironment: The Impact of Adrenergic Stress on Cancer Cells, Immunosuppression, and Immunotherapeutic Response
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325998/
(Eng, 2014)

Sassy: This quote from the conclusion will allow quick access to the studies related to breast cancer." In several clinical studies examining breast cancer, melanoma, and ovarian cancer patients, researchers have found that use of β-blockers improved long-term patient survival independent of other medications taken [6, 7, 108, 109].

Sassy: this study goes to the head of the pack. It's a review of all previous studies. This is the study that you need to have your docs read. Eventually this will be the highlighted study here. But my goal today is just get through the studies to see which ones have direct value.

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Beta₂-AR antagonist seemed to be the most cytotoxic β-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent.
http://www.tandfonline.com/doi/abs/10.3109/13880209.2014.892513?src=recsys
(Iseri, 2014)

Sassy: I have to get access to the full study. The abstract doesn't say In vivo( mammal) or invitro(test tube) Basically moving on. The discussion in the abstract refers to cell lines. So, this study is either in vivo in vitro. Not that I'm a lazy researcher, but I don't care anymore about in vivo and invitro. There is enough of a connection I want to know results of human trials. This study will likely be deleted, but it's useless right now. In general, this study compared propranolol to tenolol. Propranolol showed superior results.

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Adrenergic receptor β2 activation by stress promotes breast cancer progression through macrophages M2 polarization in tumor microenvironment
(psychological stress)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578570/
(Qin, 2015)

Sassy: Mouse study. In vivo & in vitro, with some application to human breast cells tissue cultures. From the abstract conclusion " Stress and its related hormones epinephrine (E) and norepinephrine (NE) play a crucial role in tumor progression. Macrophages in the tumor microenvironment (TME) polarized to M2 is also a vital pathway for tumor deterioration. Here, we explore the underlying role of macrophages in the effect of stress and E promoting breast cancer growth. It was found that the weight and volume of tumor in tumor bearing mice were increased, and dramatically accompanied with the rising E level after chronic stress using social"

This study has built upon earlier research.. It will be used by other researchers as a source. Nothing useful for us.

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β-Adrenergic Receptors : New Target in Breast Cancer
http://www.apocpcontrol.org/paper_file/issue_abs/Volume16_No18/8031-8039%2011.2%20Ting%20Wang%20%20%5BMINI-REVIEW%5D.pdf
(Wang, 2015)

Typing and revising

Hi Falls, glad to see you. I'm going through each study one at a time and giving an opinion. Sure wish it was a rule that studies identify in the the first three words "In Vivo, In vitro. And if In Vivo if it's a mouse study or human.

We will have to have a meeting about what to leave here and what to delete.

But I've learned that when I start to feel puffy, I've been at the computer to long. Going for a swim

Hugs sassy

Yeah but, yeahbutt. Inderal and Tenormin are both Beta1 and Beta 2. So, that study was interesting. But I think paring it down particularly since folks may be running off copies as we speck. So far I have seen a prospective human trail. The second article references it, but didn't link it.

The first article I linked is a mouse study. Again, it didn't indicate in the article. Shame on them and shame on me. You know I always go through a full study before linking it, plus putting the companion article. Broke my own rule and smash/clang boom.

The person citing the "protocol" for use Jessica Cote did this based on possibly the other article b/v I recognize it from being in their study.

I have to change the topic box. Now

Falls, I'm done for the day. Not sure if I will work this week end. The only study older than 2010 is the baseline study of 2001. I'll think about value before I suggest deleting. It's a study that a researcher needs to add into their work on this subject, but to us "clutter". Hate to say delete without thinking on it. Specially, since I gave x minutes of my life to reading it. Hahahahaha.

The outcome here, I think, is going to be similar to Toradol. Strong retrospective metanalysis in the City of Hope study. We just have to follow the breadcrumbs.

I revised the topic box and deleted all of Cote's material. There's a lesson.

PM I sent to someone on June 5th, putting it here now to work on

https://www.sciencedaily.com/releases/2016/03/160301131105.htm

.beta blocker : Beta 2 adrenoreceptors are on the cell surface of TNBC.

From the article "To make their discovery, Halls and colleagues examined how an aggressive triple negative breast cancer cell responds to the stress hormone adrenaline. They found that an aggressive breast cancer tumor cell has a cell surface protein called "beta2-adrenoceptor" that can binds both beta-blockers and the stress hormone adrenaline. When bound to adrenaline, the beta2-adrenoceptor on these tumor cells stimulates a positive signaling loop to accelerate invasion. When bound to beta-blocker, however, the accelerated invasion of these cells was decreased."

I love the drug class. They are the work horse drugs of cardiovascular care. They didn't say what drugs would be used. I won't go into a dissertation. The absolute contraindication for use of a beta 2 blocker and a beta blocker with 1&2 blocker ability would be asthma.....COPD(relative contraindication). Other than that it's profile is pretty damn good.

Beta blocker with NSAIDS and VitaminD......................Beta2 blocker slows it down, NSAIDS anti-inflammatory, vitaminD immune support. Not a cure, but interferes enough with cell proliferation it could slow it down.

https://clinicaltrials.gov/ct2/show/NCT00502684?term=propanolol&rank=143

Purpose

Surgery for breast cancer has a major role in enhancing long term survival and cure, but several physiological aspects associated with surgery are implicated as enhancing tumor spread and formation of distant metastases. These include: an increase in pro-angiogenic factors, direct spread of tumor cells, accumulation of grown factors, immune suppression and direct effects of anesthetics and opiate pain relievers on cancer cells. Some of these pro-metastatic mechanism may be blocked by the interventions proposed in this study, namely by administration of beta-adrenergic blockers and COX2 inhibitors around the time of surgery.

Studies have shown that surgery increases levels of catecholamines and prostaglandins, which in turn may promote the release of pro-angiogenic factors such as VEGF, and enhance vascularization of micro metastases.

Opiates given for pain relief during and after surgery have been reported to enhance tumor cell division and cause immune suppression.

The immune system is significantly suppressed during surgery. This suppression has been shown to affect the systemic resistance to infection as well as neoplastic metastatic processes.

Several studies have shown that increased levels of catecholamines and prostaglandins add to the immune suppression.

Studies in rats found that peri-operative administration of the beta beta-blocker propranolol together with the COX2 inhibitor etodolac significantly reduced the suppression of NK cell activity as well as the risk for distant metastases.

A recent retrospective clinical study found that among breast cancer patients treated with a combination of regional anesthesia and a COX inhibitor the recurrence rated were significantly less than among patients undergoing surgery without these two interventions.

The purpose of the proposed prospective trial is to examine if peri-operative administration of the combination of a beta-blocker together with a COX2 inhibitor will prevent suppression of cellular immunity, decrease VEGF levels, and decrease cancer recurrence rates.

In the proposed study breast cancer patients will be treated with a combination of a beta-blocker and COX2 inhibitor (or placebo) before, during and after surgery. (A control group of healthy women will serve as untreated controls). The variables which will be examined are: number and activity of NK cells, levels of Th1 and Th2 cytokines, serum stress hormones and angiogenic factors, and the ability of leukocytes to produce Th1 and Th2 cytokines as a result of in vitro stimulation.

In addition to these immediate parameters, long term follow up will be conducted in order to determine the effect of the intervention on long term cancer recurrence over five years.

Statistical analysis will be done using t-tests, ANOVA, and multivariate regressions, with regard to the known risk factors for recurrence such as tumor grade, lymph node involvement etc. Sample size for immunological parameters will be 40 patients in each group and 20 healthy women. Sample size for estimates of cancer recurrence at five years of follow up wiil be 460 women (230 in each group). This sample size provides a power of 80% to detect a 50% reduction in cancer recurrence at an α of 0.05.