thought provoking hypothesis--?new way to treat breast cancer

[Lani]

This article is by well respected breast cancer researcher Dr. Hrushesky

1: BMC Cancer. 2009 Jan 8;9(1):7. [Epub ahead of print]

Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer.

Retsky MW, Hrushesky WJ, Gukas ID.
ABSTRACT: BACKGROUND: Women with Down syndrome very rarely develop breast cancer even though they now live to an age when it normally occurs. This may be related to the fact that Down syndrome persons have an additional copy of chromosome 21 where the gene that codes for the antiangiogenic protein Endostatin is located. Can this information lead to a primary antiangiogenic therapy for early stage breast cancer that indefinitely prolongs remission? A key question that arises is when is the initial angiogenic switch thrown in micrometastases? We have conjectured that avascular micrometastases are dormant and relatively stable if undisturbed but that for some patients angiogenesis is precipitated by surgery. We also proposed that angiogenesis of micrometastases very rarely occurs before surgical removal of the primary tumor. If that is so, it seems possible that we could suggest a primary antiangiogenic therapy but the problem then arises that starting a therapy before surgery would interfere with wound healing. RESULTS: The therapy must be initiated at least one day prior to surgical removal of the primary tumor and kept at a Down syndrome level perhaps indefinitely. That means the drug must have virtually no toxicity and not interfere meaningfully with wound healing. This specifically excludes drugs that significantly inhibit the VEGF pathway since that is important for wound healing and because these agents have some toxicity. Endostatin is apparently non-toxic and does not significantly interfere with wound healing since Down syndrome patients have no abnormal wound healing problems. CONCLUSIONS: We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.
PMID: 19133151

[StephN]

The conclusion just BLEW my mind!!!

CONCLUSIONS: We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.

Particularly the part about NO ADJUVENT TREATMENT BEING NECESSARY. And NO ACQUIRED RESISTENCE. This is amazing if they can get it to work.

And we had this discussion about micromets escaping from surgery or even biopsies more than once here. This being a major reason to do chemo and radiation even if nodes are negative.

So, what can we expect on this, dear Lani??

[Lani]

I do know that endostatin is available in China. I had heard Judah Folkman talk about it. Found the following:
http://www.childrenshospital.org/res...9P27sublevel30. html

[AlaskaAngel]

The question that comes to mind for me is, would the difference in endostatin also happen to contribute to the Down syndrome or similar problems (such as chemobrain due to lack of adequate oxygenation from having less angiogenesis, or fewer blood vessels)? Can you have the beneficial effect without the detrimental effect?

I don't want to confuse the concept of reducing angiogenesis with mental meanderings -- but I have speculated as to the reasons why at 7 years out I am still NED (especially since I have not had trastuzumab). One basis that I've wondered about that may be related to blood vessel development is the fact that since starting treatment in 2002, my blood counts have stayed just below normal. I also refused the use of ESAs during treatment, and those would have brought my counts back to normal (or far above normal) during treatment. The effect of that was that my chemo was delayed all 6 times until my counts increased just enough for another dose. It also meant that the duration of low counts was much longer than it was for other patients. If that contributes enough to the lack of angiogenesis, then perhaps my choice not to use ESAs during treatment and the resulting continued low blood count has helped me out and may be continuing to do so.

[Lien]

Interesting concept, but how can they know the outcome before it has been tested? How would the know there are no side-effects? It seems to me they are assuming this, but is there any real proof?

Sorry to be sceptical. I do like the idea & think it should be investigated. But I don't think we can be sure about long term effects. Do we know why people who have Down's syndrome never used to live all that long?

Jacqueline

[Lani]

"These qualities made endostatin attractive to the Chinese, who have one fifth of the world's new cancer cases. Unbeknownst to Folkman and colleagues, a Chinese research team began studying endostatin soon after its discovery, forming a biopharmaceutal company, Medgenn Ltd., in 1999. Encouraged by the Chinese government, Medgenn modified endostatin to make it easier to manufacture and to last longer in the body, and began large-scale production. The modified drug, called Endostar, will now be tested against other cancers."

Successful and unsuccessful treatment with endostatin in China has not shown it to be associated with significant side effects and Dr. Folkman treated some
patients with endostatin as far back as the 1990 without ill-effects.

Amazon has a fabulous book on Judah Folkman as well as a PBS special on his work (he died a year ago this month-- the greatest loss to the world of cancer research I know of)

He himself was disappointed with various antiangiogenics and hypothesized it was because there was such a large number of angiogenic substances it would probably turn out to be necessary to figure out which was important for any particular tumor and block those.

I would suggest that before you give up on this--and it was published as a hypothesis only--you inform yourself further. The book and CD from Amazon are great starts (can probably get them from your local library)

The book is truly an easy read--my 86 year old mother has borrowed my copy and finds it easy to pick up on and off (still has not returned it), others have read it cover to cover immediately because of its readability

[Lien]

Thank you Lani, that sounds a lot more promising. I wouldn't be able to get the book easily here in the Netherlands, so I rely on your info. BTW I didn't doubt the methods' potential, just the claim that there would be no or few side effects. In my experience, these only show up after long term extensive testing.

Love

Jacqueline