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dbredes

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explorer
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This is a url to a study regarding CNS and triple negative
http://www.oncologystat.com/journals/journal_scans/Sites_of_Distant_Recurrence_and_Clinical_Outcomes_in_Patients_With_Metastatic_Triple_Negative_Breast_Cancer.html

What is shocking about it...isn't the CNS survival...but the  the overall survival stats...

116 triple negative patients followed 34.1 months ....12 alive - 104 dead...

Can anyone shed light on this...why the poor survival rate?

I know the survival rate is not the point of the study..but I still find it shocking...am I reading it wrong?....


dbredes

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explorer
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Please copy the entire link below to get to the webpage..
The url is too long...and is being wrapped to 2 lines...please copy the entire...url which ends in html...

to get to the article.

http://www.oncologystat.com/journals/journal_scans/Sites_of_Distant_Recurrence_and_Clinical_Outcomes_in_Patients_With_Metastatic_Triple_Negative_Breast_Cancer.html

nosurrender

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Reply with quote  #3 
Hello,
Welcome to our forum!

To answer your question, the way studies read always have that rather somber and distressing conclusion. Why? Because it is a culmination of patients studies with and without the best treatment. They have to include all. They also have to include the most dire cases mixed in with the treatable ones.

THE ONLY STUDY that is accurate is the one that hasn't come to a conclusion yet... meaning- there is SO MUCH NEW INFORMATION coming out, that only very few study have reached their practical endpoints.

You should concentrate on what keeps metastatic patients disease free  - for that is the cancer dance that is occurring now. One treatment works at keeping you disease free- FOR A WHILE- and then it is time to move to the next one. It is what they call being nimble. This means we, as patients, in partnership with our physicians, need to be nimble and stay two steps ahead of the cancer. This means changing meds at certain intervals.

What you quoted above is the result of patients who stay on only ONE med and do not change, thus the poor outcome.

There are many, many drugs out there and the dance continues.... it is hard to keep dancing, but when you are winning against the beast, let the beat go on.


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coco

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Reply with quote  #4 
Great advice for all of us, G.
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Limner

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Reply with quote  #5 
Dear dbredes - I can hear your flute!
 
Your questions about this study remind me of why I do most my reading right here at NO SURRENDER!!!!!!!!!!!!!!!!!!!
 
I don't need the negative energy and worrisome thoughts - I need real facts and hopeful vision, and I find both on this site with Gina and Constantine K., both brilliant and dedicated to a keenly focused purpose.  Between them, the resource is priceless.  They know the field inside-out, and compassionately synthesize all the medical information and patiently spoon feed it to us, while offering genuine emotional support.  
 
I am so glad you found this resource, too.   We all say we wish we had found it sooner - Have you seen Constantine's (Edge) posts on 3N disease?  All that matters is you and your body, your choices - and this moment.   Keep playing that flute for us -  Mary

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Dear friend, theory is all grey, and the golden tree of life is green. - Goethe
Limner

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Reply with quote  #6 
This is great copy/paste from a post by C/Edge on 6/08, shining a bright light on some facts about 3N and our part in healing.  These in-depth analyses of his can be hard to find when you want to refer to them.  M
 
Dueling Data and the Intrinsic Limits of Precision on Outcome
Straight out let's understand that there simply is no single fully evidence-based single consensus on outcome events, risk and prognosis for triple negative disease, and multiple divergent views knock about in uneasy companionship. So for instance most professionals (but not this one) appear to accept the authority of the landmark paper ("The Triple Negative Paradox") on this issue by Lisa Carey at UNC. In that study, the estimated 4-year distance disease free survival (DDFS)
was 71% for women with basal-like tumors - the closest to triple negative status in the study - with a range of 51 - 84%, compared to HER2+/ER– with 51% (18 - 77% DDFS) and luminal (A + B combined) with 82% (64-91%) DDFS. But apparently overlooked by most professionals is the fact that the patients included in the study's data set were treated between June 1998 and October 2003, representing to this researcher a deprecated era of older regimens with little modulation from either the new and more penetrating insights drawn from the recent genomic era of molecular research nor from the new and smarter oncotherapeutics of triple negative disease. Each year we get smarter, so each year, hopefully, in the aggregate, patient treatment should be more and more optimized and finely honed, to the outcome favor of the patient.

Now, a larger cohort was studied by Bruce Haffty with the Cancer Institute of New Jersey / UMDNJ-Robert Wood Johnson Medical School which found that at 5-years, the 5-year distant metastasis-free rate of the non–triple negative patients was 82 - 88% compared with 67 - 79% in the triple negative cohort. Again for 5-year, if we look at the overall survival rate, not at the specialize metastasis free rates, overall survival is 80% for women with triple negative disease compared to 89% for women with non-TN tumors. And as to the further horizon of the 10-year overall survival rate, that was 73%, while the 10-year local relapse-free rate was 78%, the distant relapse–free rate was 71%, and 10-year cause-specific survival rate was 75% (all in TN patients).

And although the comparison of an 80% overall survival rate for women with triple negative disease compared to 89% for women with non-TN tumors is widely bandied about, two things are imperative to note here: (1) in fact, the difference between overall survival for women with triple negative disease and those without is not statistically significant, that is, the overall survival of the 482 patients studied was not significantly different for triple negative disease than that of the overall patient population; and (2) these numbers derive from a retrospective study of women treated between 1980 and 2003: we have grown much smarter (technically, highly granular) in our oncotherapeutics of triple negative disease. But in any case, although the fervent wish and goal of everyone engaged in breast cancer research and treatment is to have 100% survival, nonetheless an 80% 5-year overall survival rate should not be psychically paralytic - it's a portal through which most (4 out of 5) women will pass successfully, and as I have indicated, it is clinically much quieter on the other side - risk plummets dramatically after the peak risk period (roughly the first 3 to four years) and the rise in prognosis is extremely heartening, and nor is there an appreciable residual chronic and persistent per annum recurrence risk as there is typically in endocrine disease.

Still another set of survival statistics that are widely cited are those of Bas Kreike with the Netherlands Cancer Institute, reported late 2007, where based on a published series and the authors own research, it was estimated that 55 - 70% of patients with ER-negative breast cancer will not develop distant metastases at the ten-year follow-up point (that is, 10 year relapse-free survival (RFS) = 55-70%). The study itself found a 5-year metastasis-free survival (MFS) for TN patients (71) of 74%, but I have argued in critically appraising the study that this is assuredly a serious underestimate since I note that although the tumors were all ER-negative, 21% of the patients I discovered were actually treated with tamoxifen, wholly inappropriate as I observe, the study population being patients treated between January 1985 and February 2005 and in the earlier time periods of that stretch, tamoxifen deployment was not (incorrectly) restricted solely to hormone-positive disease.

Countervailing Factors
In addition, however, it should be noted that the 5-year metastasis-free survival for node-negative
TN patients was 86%, while this rises to 88% for patients with a moderate or extensive amount of tumor
lymphocytic infiltrate, and to 100% for patients with an extensive component of lymphocytic infiltrate, that is, none of these developed distant metastases at all, and finally the 5-year metastasis-free survival for patients with no central fibrosis in their tumors was 97%. In fact there are four histopathological groups that can be differentiated on the basis of the variables of amount of lymphocytic infiltrate and central fibrosis, and all patients in the most favorable group with moderate-extensive lymphocytic infiltrate in combination with no central fibrotic zone remained free of metastases completely. According to a multivariable Cox proportional hazard analysis conducted, only lymphocytic infiltrate and central fibrosis are independent risk factors for metastasis-free survival in patients with triple-negative tumors, as I discussed more extensively in my separate coverage of this issue in my Triple Negative Tutorial. And there was also a trend towards an improved metastasis-free survival for tumors with increased expression of interferon-regulated and immunoglobulin genes (these reflect activity of the immune system).
 
The Contrarians
Even more critical to remember is that as Eriko Nakano with the National Cancer Center (NCC) in Japan shrewdly observed at ASCO 2007: "Although triple negative breast cancer has been considered to have a poor prognosis, there is no evidence to back up the assumption". The NCC team studied 750 patients from March 1999 to August 2002, of which 48 were TN patients, and of these 48, at a median follow-up time of 4.9 years 9 were relapse cases, 2 being local-relapse and 7 being distant-relapse, yielding a distant metastasis-free (DMF) rate after 5 years of 85%, leading the authors to conclude that there was no significant difference in 5 year survival between triple negative and the rest of the non-TN population, and this is in agreement with just reported results at ASCO 2008 (May 20) from Turkish researchers Devrim Cabuk and colleagues that not all patients reviewed with triple negative disease had poor prognostic features as the literature would otherwise suggest. And we know from the Cornelia Liedtke team of MD Anderson researchers reporting earlier this year (March) (by and colleagues), that patients with triple negative disease have increased pCR (pathological complete response) rates in response to neo-adjuvant therapy compared to non-triple-negative patients, and that furthermore those with pCR actually have excellent prognosis and survival, once more agreeing with the independent and as yet unpublished findings of Cecilia Mercado at NYU as reported at the Annual Meeting of the American Roentgen Ray Society (ARRS).
 
The Tangled Web, Again
And of course there are a dizzyingly large number of factors in play here across racial/ethnic, genetic, molecular, histopathological, biological (age, obesity, and other status) and many other variables, including clinical history, molecular class (basal versus non-basal) and BRCA status, to name only a few out of dozens and dozens woven together into an intricately weaved and meshed fabric which even then is only partially determinative of any individual's risk and outcome.

__________________________________________________ ____________________________________

One brief note before concluding: As to the importance of tumor locality and "quadrandature", I addressed that in the thread Does Quadrant location of Breast cancer matter?. But rather than taking up any other themes here, I'll put the above analysis out for reflection and discussion, and then take up any specific questions springboarding from it.

Eine Kleine Lesson, and Not So Kleine Hope
And I'll leave one thread of thought for reflection: we know a good deal about the underlying pathways that are critical in the metastatic cascade as it called. For example, simplifying greatly, the COX pathway is critically exploited in metastases to the lung, liver and bone, the LOX (lipoxygenase) pathway is exploited in the pathogenesis of metastases to the brain, while NF-kB (Nuclear Factor kappa-b), the PI3K/Akt/mTOR kinase pathway, Wnt, Hedgehog, Slug, Snail and Twist among many others (some with even more fanciful names) are active at multiple junction points of the metastatic cascade. But so what, one can ask?

Well, I'll take one small example: Just reported by Fabrice Andre with the Institut Gustave Roussy at ASCO 2008 was the spectacular result that the mTOR inhibitor, everolimus, completely remitted all brain metastases in a patient refractory to multiple levels of oncotherapy. Now, I'm properly - but not overly - impressed, as I've been obtaining similar results by advising use of the pharmaceutical grade of the natural LOX inhibitor boswellic acid (derived from the gum-resin of the Ayurvedic plant Boswellia serrata (Frankincense)) to anyone who will listen (few, but some do) for both active therapy, and natural prevention, of brain metastases, and in this small but growing tradition the great Dan Flavin with the Foundation for Collaborative Medicine and Research has used this natural molecular-targeting LOX inhibitor to completely reverse multiple brain metastases in a breast cancer patient who had shown no improvement after standard treatment. So now, concerned as we are about potential brain metastasis in triple negative populations, we can wait for the investigational mTOR inhibitor everolimus (Certican) to wind it's way out of the regulatory pipeline into the breast oncology community, or we can get acquainted with boswellic acid intervention. Ditto for the concern over lung, liver and bone metastases: we can agitate for a COX-2 inhibitor - celecoxib (Celebrex) - or seek a clinical trial of such; but we can also deploy curcuminoids, natural COX-2 inhibitors at least as powerful, and which also intervene positively against mTOR, NF-kB (Nuclear Factor kappa-b), the PI3K/Akt/mTOR kinase pathway, Wnt, and Hedgehog and dozens of other pathogenetic pathways influencing the metastatic cascade, as well as being active against the underlying UR-pathway, the insulin (IGF) pathway (also addressable by exercise that mitigates against sarcopenic obesity, and by tight glycemic dietary control, and by another UR-substance, melatonin).

We are only victims of ourselves if we wait for metastases - we can draw the battle lines early and we have weapons of our own.
Never go unarmed to battle with a foe as sinewy and stealthy as cancer.


Constantine Kaniklidis
Breast Cancer Watch
edge@evidencewatch.com


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Dear friend, theory is all grey, and the golden tree of life is green. - Goethe
nosurrender

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Reply with quote  #7 
Mary, I think I might have to change your nickname.... I do that sometimes when you all least expect it...
you are such a great Resource Librarian here- you find just the right post from way back in the archives just when we need it most!

hmmmmmmmmm.....
I have to think about this!

Love
g


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MsBliss

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Reply with quote  #8 
Thank you for posting this!

It is brilliant....

The info is priceless, esp the tips at the end.
MsBliss

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Reply with quote  #9 
Many thanks for posting this.  I can never find Edge's work for some reason; and I really need to refer to it.
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