Tamoxifen for 10 years cuts breast cancer relapses...

Beesie...I wonder if with this new study if women who finished their 5 years of tamoxifen more than 5 years ago, might consider taking it again for 5 more years and THEN maybe we might actually see your hypothesis in action.... Got to wonder what oncologists are recommending since the announcement....

I also wonder how this might affect the Oncotype DX score which bases its scores on 5 years of Tamoxifen....Hmmmm.....

Cp418... Want to dig up if there is a current trial or is this going to be meta/ retrospective analysis? I don't recall reading in the NCCN guidelines about any of that type of trial... I will take another look... I know my doctor initially told me I would be offered 5 years of Tam followed by 5 of an AI, although there want any conclusive data supporting it. He said we'd have time to wait and see.... Since the Atlas report, I've been wondering if he will recommend 10 years of Tam while we wait for more data. Somehow I think I am staring at 10 and 10 if I live so long....





Regarding a gap not being an issue.... I don't think a gap is an issue per se. I think the question that we would all like answered, which Beesie so eloquently describes is how do we get the most bang for the buck with the fewest side effects?



I am STILL envisioning a future where based on genomics we will all know how much of a therapy is enough for all of our individual cases....

kyliet - because of your co-morbidity I am confident in strongly urging you to try Lupron first to see if you can tolerate it before going for an ooph, which is irreversible. Ask for a low dose to begin with.

Now here's an interesting study.  It calls for 5 years of an AI with "gaps."  The SOLE trial:

"In 2006, the standard duration of adjuvant endocrine therapy for breast cancer
(either selective estrogen receptor modulators [SERMs] or aromatase inhibitor
[AI]) is five years. Patients who receive extended adjuvant letrozole for five
years following approximately five years of tamoxifen obtain further benefit
compared with the five years of tamoxifen alone. Similarly, benefit has been
demonstrated for switching from tamoxifen to an AI after 2 to 3 years of
tamoxifen to complete five years of endocrine therapy, as well as initiating
therapy with AI following surgery and administering the AI for five years.


Questions remain about the optimal duration and best schedule of AIs in
the extended adjuvant setting. This trial tests the hypothesis that introducing
3-month treatment-free intervals during the course of five years of extended
adjuvant letrozole will improve disease-free survival. This hypothesis is based
on the theoretical principle that letrozole withdrawal for 3 months will permit
some estrogenic stimulation which makes residual resistant disease susceptible
to letrozole reintroduction."

To get into the trial, patients must have completed 4-6 years of endocrine therapy and must be randomized within 12 months of completing the 4-6 years.  The results won't be known until 2021. 

This seems like an interesting study and takes into consideration "gaps."  It's also interesting to note that there can be up to a year long lag before entrance into the study...I wonder where this information will be noted when they crunch the numbers....

Furthermore, I read this interesting commentary by Steven Vogl, MD, that speaks to many of the issues we are discussing, specifically about identifying those patients who would clearly benefit from added therapy, as opposed to those who won't.  I thought this statement to be the most provocative:

"Recent data suggest that simple available tests may identify an estrogen receptor–positive population that does not benefit from adjuvant tamoxifen. Low levels of ESR1 mRNA measured in the Oncotype DX test correlated with no discernible benefit from tamoxifen in a retrospective subset analysis of NSABP B-14.¹⁶ Any study of new extended adjuvant hormonal therapy should look at gene expression profiles at diagnosis. If low ESR1 mRNA levels indeed define a group of patients resistant to hormonal intervention, we not only will spare them toxicity, expense and inconvenience, we may enter them into trials seeking effective therapy for them.

Data presented at the San Antonio Breast Cancer Symposium in 2011 suggest that gene expression profiles differ in patients who relapse after five years compared with those who relapse earlier while on tamoxifen.¹⁷ These differences are somewhat difficult to interpret because some may be beneficial in that they are associated with delay of early relapse, rather than being deleterious by favoring late relapse as compared with no relapse. Other potential ways to choose patients for extended adjuvant endocrine therapy were suggested by Eric Winer, MD, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston, in a superb lecture in San Antonio in December 2011, including bone marrow tumor cells and circulating tumor cells measured at diagnosis or at possible crossover."

I think Dr. Vogl's perspective is welcoming.  It speaks to the issue of using genetic markers in helping us decipher who EXACTLY is benefiting from treatment....

Here's the commentary:

http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid+Tumors&d_id=148&i=January+2012&i_id=808&a_id=20054

Enjoy reading!

here! Here!!  I agree...what do we do now.

I am still a little unnerved by the article that stated that lobular cancer did not benefit as much from tamoxifen...so 10 years of (I had pretty bad side effects) hell for a "maybe" benefit just seems icky.

Oncotype DX tested for chemo benefit, but assumed you would do tamoxifen, so even that didn't really look at the genomic detail as much as is available now.  I wonder how many side effects women will discover years down the road from AIs.

I realize I, as others here, voice all of our concerns.  It is nice to come here and realize I am not the only one confused and frustrated and still questioning.....

I've been on Tamoxifen for about 7-8 months now.  I am not suprised that they are changing the recommendations about T treatment duration.  I think its a very important part of our treatment.  It will be interesting to see how this evolves. 

http://www.medicalnewstoday.com/articles/127571.php

here's a study from 1996, that says that 5 yrs of tamoxifen is optimum, and that 5 more years doesn't matter.  

http://www.ncbi.nlm.nih.gov/pubmed/8901851

However, it seems the difference btwn the above study from '96 and the recent 2012 one is that the recent one looked at longer term survival, out 15 yrs, versus 10.

Okay. Don't get me wrong: I love, and am so grateful, to every researcher/scientist/doctor laboring over curing and treating cancer. I owe them my life, more than one time over.  But I do wonder: why did it take so long to figure this out?  Clearly, in 1996, (whether women were routinely tested, told and treated according to E+/- is less relevant) the researchers had that information about E receptor positive/negative and  accessible to them and were using it.  So happy for someone to point out the 'duh' in what I'm posting, that quickly explains why they couldn't just take this study and look at it 5 more years later (giving us the info in 2001 instead!).  Waiting for someone to show me the light, which I'm sure someone will soon. !

Jessica...Below is a press release from the 2007 San Antonio Breast Cancer Symposium discussing preliminary findings of the Atlas trial.  It would appear that shortly after the recommendation was made that 5 years of Tamoxifen should be the gold standard, there must have been questions raised about the NSABP B-14 that made the recommendation, because the Atlas trial commenced in 1996.  Now, if the trial commenced in 1996, IMHO, it must have been designed and funded prior to 1996.  According to the Atlas 2012 study published in the Lancet, recruitment for the trial began in 1996 and continued through 2005.  The entry point in 1996 included patients who had already completed 5 years of tamoxifen and then were randomized to either continue taking it or stop.  If you read below's press release from 2007, you will see some of the issues that the researchers faced in confirming the effectiveness of 10 years over 5 years of Tamoxifen.  The year 2007 is very pivatol in the study because that was the 10 year mark of the first patients who were recruited into the study.  The researchers clearly saw that the "numbers" were starting to favor 10 years.  But it is now 15 years into the study and the "numbers" are now statistically significant. So, to answer your question, why did it take so long?  The answer is simple.  It takes years if not decades to determine the clinical significance of a trial.  And if you have a trial that is comparing something over a 10 year period, it is not unlikely that it would take another 5- 10 MORE years to see a significance.  One of the drawbacks of clinical trials is that they often take too long to conduct and another even larger problem is that quite often they aren't completed because they can't get enough patients to join the trial.  In his book, The Creative Destruction of Medicine, Eric Topol, MD discusses the drawbacks of clinical trials and envisions a day coming soon that genomics will make long, drawn out AND EXPENSIVE trials obsolete.

So, the short answer to your question as to why did it take so long and why couldn't we have known the answer back in 2001 is, because beginning in 1996 they first had to recruit another group of patients to begin taking another 5 years of tamoxifen.  And that took another 5 years to complete!  So, there weren't enough patients to power the trial until 2001!  And then they were FIRST able to BEGIN calculating if there were any differences after that.  If you recall, the differences became significant around the 12th year mark (which would be 2007...the year of the press release) and that's why the interium results were published.  Then they needed the additional 5 years to CONFIRM it which brings us to 2012.

________________________________________________________________________

Ten Years of Tamoxifen Better Than Five: Presented at SABCS
By Janet Fricker

SAN ANTONIO, TX -- December 17, 2007 -- The recommendation to limit adjuvant tamoxifen treatment to 5 years may have been premature, suggest results of a study presented during a late breaking special session here at the 30th Annual San Antonio Breast Cancer Symposium (SABCS).

The Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, a large international study, compared the efficacy and safety of 5 years versus 10 years of adjuvant tamoxifen treatment. In the study 11,500 women from 400 international centers who had been taking tamoxifen for 5 years were randomized at year 5 to continue taking tamoxifen to 10 years or to stop treatment.

Presenting the data, Sir Richard Peto, MD, Clinical Trials Unit, University of Oxford, Oxford, United Kingdom, pointed out the limitations of the study. Only 59% of the patients were definitely estrogen-receptor (ER)-positive; the remaining 41% were not tested for ER status.

Of the untested women, around one quarter are likely to have been ER negative, and hence are unlikely to experience benefits from tamoxifen. In addition there were site-to-site differences in compliance rates, Sir Richard said.

"The upshot is that ATLAS only shows around 72% of the true effect of tamoxifen," he said.

Nevertheless, despite such limitations, results show that a trend towards decreased recurrence and breast cancer mortality is beginning to be seen at 5-plus years in the 10-year tamoxifen group compared with the 5-year tamoxifen group.

"This interim analysis does make it very likely that continuation of tamoxifen would produce clinical benefit," said Sir Richard, adding that the current recommendations to limit tamoxifen treatment to only 5 years, which were based on data from National Surgical Adjuvant Breast and Bowel Project (NSABP) study B14, is likely to have been premature.

"The numbers in NSABP B14were too small to justify dismissing the important question of whether continuing tamoxifen beyond 5 years could, in the long run, moderately reduce the recurrence rate," said Sir Richard. "The new ATLAS data suggest that longer-term use is likely to produce benefits." .....

http://apps.komen.org/Forums/tm.aspx?m=184217&mpage=1&print=true

Oh this is annoying.  So first, they say cyp2d6 and tamoxifen matter.  Then they say, it makes no difference  and just take the tamoxifen...and now back to it matters.  REally???

Plus, the link stated "faulty"...but did not define that.  As I recall there were intermediate metabolizers, full metabolizers and no metabolizers.  Are they calling "faulty" as non -metabolizers or is intermediate included in there?

UGH.  I guess I was "lucky" to get my cancer at the cusp of aromatase inhibitors and my becoming menopausal.  So doing 3 years of tamoxifen (and god knows if it did anything for me since I am an intermediate metabolizer AND I had lobular cancer) and 2 years of an AI...though now the stories I am reading are saying I should have taken Femara and not arimidex. 

Does this fresh-hell never end??

Susans garden i too am goingto ask my onc about that cyp26 test( tried to state it from memory could be wrong on what it's called) because hey I want to know if I metabolize tamoxifen, otherwise I will willingly put myself into menopause at 31 in order to go on ai. Because all in all no recurrence is important for me and I want my life,



Guess that would predetermine my use of tamoxifen or not..... just wanna share

When I brought up this report on tamoxifen for ten years rather than five to my mo, she said that she would not keep me on tamoxifen for only five years. She stated that study was likely funded by AstraZeneca, the makers of tamoxifen and also after five years would increase risk of uterine cancer. She was adamant, however, on keeping me on hormonal therapy for up to 15 years. I am 31 and she mentioned pushing me into menopause after the five year tamoxifen period ( and hopefully after kids, at least two years on tamoxifen,kids, then another 3 years).. Then chenically induced or surgery induced menopause, so I can take the ai's. they say the post menopausal ai's are great. I am not keen about going into menopause at 36 or 37, but I am keen on not letting this bc come back, so I am ok with hormonal therapy for 20 years haha. Thanks for listening.. Would love some feedback...

Hey who knows what other studies will come up in the next few years... I didn't even finish chemo yet

Also I wrote earlier

I suppose that cyp2d6 test is still being studied.. It seems tomakes sense me that the stronger the er/pr positivity the more tamoxifen would work for the benefit.. But i have never seen if this is accurate..llDoes anybody else think that makes sense or agree with me? Wouldn't e higher the positivity mean the more these horomone therapies would work.

Hate breast cancer!!

I'll take 10 years of Tamox if it'll keep me alive that long. I am an ultra rapid metabolizer so if it were just a question of metabolism it should work for me. I also don't know what this means for toxicity. I'm just betting the benefits outweigh the risks. My onc has me on 10 mg a day as opposed to 20 so he probably is taking into account my metabolism and long-term risks. Speaking of dosages, this could have something to do as well with the absolute number of estrogen receptors. The more Tamoxifen there is to bind to estrogen receptors the better. If there are too many receptors for the amount of Tamoxifen, the effect is blunted. That's just my guess. Which may not be worth anything.

Why couldn't the researchers simply continue following the people who had participated in the original trial?   Would it really have been so hard to get nearly all of them to sign on to releasing medical records for 5 more years, or to providing information over the next 5 years on mortality/disease free survival? They wouldn't have needed to reinvent the wheel and start from scratch.  It's not like the participants had to DO anything: no one had to get any additional tests or take additional drugs. Reserachers simply needed to ascertain whether or not they had DFS or a recurrence over the next 5 yrs....

Or is that naive and they need to start from scratch?