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Dr. Eliaz Responds to Questions about BreastDefend- by Ralph W. Moss, PhD.

BreastDefend Dr. Eliaz

BreastDefend stops proliferation of cancer cells

A paper on a new dietary supplement for breast cancer has appeared this week in the online version of Integrative Cancer Therapies (http://ict.sagepub.com). BreastDefend (BD) is a blend of medicinal mushrooms, herbs and nutritional compounds. In this laboratory study, Indiana University scientists showed that BD inhibited the proliferation and invasiveness of highly metastatic breast cancer cells. Particularly impressive was the effect of the highest dose of BD at 72 hours, where virtually all the cells were suppressed (see illustration).

This isn’t the first time that most of these ingredients have been shown to kill cancer cells. But by combining them in a single formula, one can use lower doses to achieve an synergistic effect. I appreciate the way the developer of the product, Isaac Eliaz, MD of Econugenics, has not just touted his product’s virtues but once again (as with his Pectasol-C) provided scientific proof.

The recommended dose is 1 to 4 capsules, 2 times a day, taken with food, or as directed by one’s health care professional. I have found it for sale on the Internet for as little as $77.99 for 120 capsules. Even at the highest dose this comes to around $5 per day, which seems reasonable for such a promising supplement.

There have been many comments and questions about the BreastDefend nutritional formula. I therefore asked the developer of the product, Isaac Eliaz, MD, to look at and respond to these. Here is his response along with questions and answers to frequently asked questions.


 

Hello to you all,

As the formulator and developer of the preparation discussed here, I would like to respond to and clarify a number of important questions that have been raised in response to this blog. As this is Breast Cancer (BCa) Awareness month and last month was Prostate Cancer (PCa) Awareness month, I would also like to take the opportunity to touch on some philosophical and practical points that are similar to both BCa and PCa, which I think can be of use in the short and long term treatment and prevention of these all too common cancers.

While in BCa we differentiate between ER/PR positive and ER/PR negative tumors with Her2-Nu being a third component leading to “triple negative” tumors, a more generalized term can be used categorizing the cancer as hormonal sensitive on one hand or hormonal resistant or hormonal independent on the other. This is commonly used in BCa and PCa to differentiate between the less aggressive estrogen positive and androgen sensitive and the more aggressive triple negative BCa and androgen independent PCa. In this context, and especially in BCa, it is important to differentiate between the primary tumor and the circulating tumor cells (CTC’s) that are responsible for the metastatic process. What we often find in BCa, is a higher % of elevated circulating tumor cells in triple negative primary BCa. (http://breast-cancer-research.com/content/12/3/402)

When the primary tumor is estrogen positive, often the CTC’s don’t have the same characteristics, being triple negative. Integrative approaches try to identify the nature of the CTC’s and will often target the initial and follow-up therapies to address both the primary tumor and the CTC’s. They apply CTC (Circulating Tumor Cells) technology, understanding that while the main tumor is ER positive, there may already be a micro component of ER negative or triple negative cells circulating in the system, and these are the cells that will cause the metastatic process. This concept is more developed in the treatment of BCa, and can play an important role in PCa as well.

So, looking at these principles, when we come to treat and prevent BCa, we need to address both categories of tumor cell expression simultaneously, both on a short term and a long-term basis.

Another important therapeutic principle is that in general, it is easier to have a response to ER positive BCa tumors and to androgen independent PCa tumors. In fact, sophisticated integrative medical approaches often try to reverse a tumor that has mutated or transformed from hormonal sensitive to hormonal resistant (and remember that this may be a ratio of expression). In PCa, it means allowing a patient that is not responding to androgen depravation therapy to begin responding. In BCa, it means allowing a patient that stopped responding to aromatase inhibitors to respond to them again.

Now, let’s look at the role that different compounds and supplements can play in the treatment of cancer. I won’t be able to cover all of them here, but I will use some examples that are included in the breast health formula discussed here.

DIM has anti proliferative effects in both ER positive and triple negative BCa. DIM has been shown to inhibit cancer cell proliferation and induce their apoptosis, working synergistically to enhance the effect of taxotere-induced cell death in cancerous breast cells through inactivation of NF-kappaB (a protein associated with cancer cell proliferation), and inhibits angiogenesis and metastasis of breast cancer cells.

Medicinal mushrooms in this formula have multiple mechanisms of actions, including immune enhancing and anti-cancer activities. Ganoderma, commonly known as Reishi, has shown anticancer effects in ER positive BCa. An example of this research can be found here: http://onlinelibrary.wiley.com/doi/10.1002/ijc.10707/pdf . These mushrooms are different, because they are grown on a blend of proprietary immune enhancing and anti-cancer botanicals, one example being Scutellaria barbata.

The principle behind this breast health formula is the synergistic action of the combined ingredients. As an example, Quercetin has anti BCa benefits for both ER Positive and triple negative cell lines. It also prevents resistance to heat shock proteins. In addition, it can prevent resistance to Adrianycin and helps to prevent MDR (multiple drug resistance). The effects of Quercetin are enhanced by another powerful anti-cancer herbal ingredient, Curcumin. Two other anti-cancer and immune enhancing herbs, Astragalus and Scutellaria barbata, are used in the formula as well. The combined antioxidant and anti-cancer action of these herbs works to prevent damage to DNA, influence the transcriptions of genes responsible for redox metabolism, and inhibit proliferation of breast cancer cells.

As for the question about triple negative breast cancer, the
MDA-MB-231 cells tested are estrogen receptor-negative (ER-negative)
progesterone receptor-negative (PR-negative), HER2/neu-negative. However, we tested the anti proliferative effects of the preparation on MCF-7 cells as well, and had comparable results.

Here is the link to the full article:
http://ict.sagepub.com/content/early/2010/09/16/1534735410386953.full.pdf

I am providing answers to some of the specific questions as well.

1) Was this compound tested against MCF-7 (estrogen dependent) breast cancer cells?

The focus of the study was against the highly invasive
estrogen receptor negative human breast cancer cell line MDA-MB-231.
The reason behind it is that it is significantly more difficult to treat triple negative BCa.
We tested the anti proliferative effects of the preparation on MCF-7 Estrogen positive cell lines with comparable response! Currently we are completing toxicology and efficacy in vivo animal studies and plan to continue with human clinical trials. We also demonstrated a synergistic effect of this preparation with MCP (Modified Citrus Pectin) in the same MDA-MB231 cell line.

2) Could someone please comment further on the response? Assuming that
a breast ca is ER+, how is it that Reishi, which the reply indicates
mimics estrogen, can suppress proliferation. Assuming that it works the
same way as estrogen I do not understand why it does not increase
proliferation, as it appears to be a substitute for estrogen. Is it
that it blocks the activity of estrogen by docking on its receptors in
the test cells and that it does not activate the cells in the same way
that estrogen works on ER+ cells. Does it act as a stub rather than an
activator?

The compounds in the Reishi appear to mimic estrogen like other
phytoestrogens, by attaching to the receptor and essentially blocking
it and having less effect than estrogen itself.

3) Is this supplement also good for triple negative breast cancer?
Yes, it was tested on triple negative cell lines. The benefits for multiple types (including synergistic effects with traditional chemotherapy) of breast cancer have been seen in the
ingredients, one example being the DIM.

Here is a list of references for DIM:

Jin Y, Zou X, Feng X. 3,3′-Diindolylmethane negatively regulates
Cdc25A and induces a G2/M arrest by modulation of microRNA 21 in human
breast cancer cells. Anticancer Drugs. 2010 Oct;21(9):814-22.
http://www.ncbi.nlm.nih.gov/pubmed/20724916

Rahimi M, Huang KL, Tang CK. 3,3′-Diindolylmethane (DIM) inhibits the growth and invasion of drug-resistant human cancer cells expressing EGFR mutants. Cancer Lett. 2010 Sep 1;295(1):59-68.
http://www.ncbi.nlm.nih.gov/pubmed/20299148

McGuire KP, Ngoubilly N, Neavyn M, Lanza-Jacoby S.
3,3′-diindolylmethane and paclitaxel act synergistically to promote
apoptosis in HER2/Neu human breast cancer cells. J Surg Res. 2006 May
15;132(2):208-13.
http://www.ncbi.nlm.nih.gov/pubmed/16580691

Ahmad A, Kong D, Wang Z, Sarkar SH, Banerjee S, Sarkar FH.
Down-regulation of uPA and uPAR by 3,3′-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells
.J Cell Biochem. 2009 Nov 1;108(4):916-25.
http://www.ncbi.nlm.nih.gov/pubmed/19693769

4) Is this also considered a preventative? What should the maintenance
dose be if treatment for ER positive BCa has been completed and
no obvious signs of cancer remain? AND no AIs or Tamoxifen are being
taken? Any tests on this product WITH hormone therapy vs. without?

Yes, it can be used as a preventative and for maintenance after cancer
treatments appear to have succeeded. The dosage would be 2 capsules, 2
times daily for 1-2 years. The dosage can then be reduced to 1×2/day, with food. . The compound is designed to work well with and without hormone therapy, and could complement each other.

This breast health formula contains a highly concentrated extract of Scutellaria barbata. There is ongoing research on the use of highly concentrated Scutellaria Barbata in BCa, now in clinical trials under the name BZL 101.

Research abstracts for Scutellaria barbata:

Perez AT, Arun B, Tripathy D, Tagliaferri MA, Shaw HS, Kimmick GG,
Cohen I, Shtivelman E, Caygill KA, Grady D, Schactman M, Shapiro CL. A
phase 1B dose escalation trial of Scutellaria barbata (BZL101) for
patients with metastatic breast cancer. Breast Cancer Res Treat. 2010
Feb;120(1):111-8.
http://www.ncbi.nlm.nih.gov/pubmed/20054647

Marconett CN, Morgenstern TJ, San Roman AK, Sundar SN, Singhal AK,
Firestone GL. BZL101, a phytochemical extract from the Scutellaria
barbata plant, disrupts proliferation of human breast and prostate
cancer cells through distinct mechanisms dependent on the cancer cell
phenotype. Cancer Biol Ther. 2010 Aug 20;10(4).
http://www.ncbi.nlm.nih.gov/pubmed/20574166

Bui-Xuan NH, Tang PM, Wong CK, Fung KP.Photo-activated
pheophorbide-a, an active component of Scutellaria barbata, enhances
apoptosis via the suppression of ERK-mediated autophagy in the
estrogen receptor-negative human breast adenocarcinoma cells
MDA-MB-231. J Ethnopharmacol. 2010 Aug 19;131(1):95-103.
http://www.ncbi.nlm.nih.gov/pubmed/20558270

Fong S, Shoemaker M, Cadaoas J, Lo A, Liao W, Tagliaferri M, Cohen I,
Shtivelman E. Molecular mechanisms underlying selective cytotoxic
activity of BZL101, an extract of Scutellaria barbata, towards breast
cancer cells. Cancer Biol Ther. 2008 Apr;7(4):577-86. Epub 2008 Jan 7.
http://www.ncbi.nlm.nih.gov/pubmed/18305410

Rugo H, Shtivelman E, Perez A, Vogel C, Franco S, Tan Chiu E, Melisko
M, Tagliaferri M, Cohen I, Shoemaker M, Tran Z, Tripathy D. Phase I
trial and antitumor effects of BZL101 for patients with advanced breast cancer. Breast Cancer Res Treat. 2007 Sep;105(1):17-28.
http://www.ncbi.nlm.nih.gov/pubmed/17111207

As mentioned, the breast health formula contains a bio-available turmeric extract
with known properties of fighting breast cancer. Here are some research abstracts for
turmeric toot extract:

Quiroga A, Quiroga PL, Martínez E, Soria EA, Valentich MA. Anti-breast
cancer activity of curcumin on the human oxidation-resistant cells
ZR-75-1 with gamma-glutamyltranspeptidase inhibition.
J Exp Ther Oncol. 2010;8(3):261-6.
http://www.ncbi.nlm.nih.gov/pubmed/20734924

Al-Hujaily EM, Mohamed AG, Al-Sharif I, Youssef KM, Manogaran PS,
Al-Otaibi B, Al-Haza’a A, Al-Jammaz I, Al-Hussein K, Aboussekhra A.
PAC, a novel curcumin analogue, has anti-breast cancer properties with
higher efficiency on ER-negative cells. Breast Cancer Res Treat. 2010
Aug 1.
http://www.ncbi.nlm.nih.gov/pubmed/20680677

Boonrao M, Yodkeeree S, Ampasavate C, Anuchapreeda S, Limtrakul P. The
inhibitory effect of turmeric curcuminoids on matrix
metalloproteinase-3 secretion in human invasive breast carcinoma
cells. Arch Pharm Res. 2010 Jul;33(7):989-98.
http://www.ncbi.nlm.nih.gov/pubmed/20661707

Research abstracts on Quercetin:

Chou CC, Yang JS, Lu HF, Ip SW, Lo C, Wu CC, Lin JP, Tang NY, Chung
JG, Chou MJ, Teng YH, Chen DR. Quercetin-mediated cell cycle arrest
and apoptosis involving activation of a caspase cascade through the
mitochondrial pathway in human breast cancer MCF-7 cells. Arch Pharm
Res. 2010 Aug;33(8):1181-91.
http://www.ncbi.nlm.nih.gov/pubmed/20803121

Oh SJ, Kim O, Lee JS, Kim JA, Kim MR, Choi HS, Shim JH, Kang KW, Kim
YC. Inhibition of angiogenesis by quercetin in tamoxifen-resistant
breast cancer cells. Food Chem Toxicol. 2010 Sep 4.
http://www.ncbi.nlm.nih.gov/pubmed/20804812

For more information on integrative cancer therapies, research and recommendations, please visit my website at http://www.dreliaz.org. Email Isaac@dreliaz.org.