Tamoxifen for 10 years cuts breast cancer relapses...

Just to be clear, my question..." WHy couldn't the reserachers simply continue following..." is in response to voraciousrea...

the study itself says taht the reaserachers wanted to know if 10 yrs was better than 5, so they continued the study to update the results.  They stated:

"We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up."  (bold added) SO WHY COULDN'T THEY CONTINUE to evaulate the outcome of patients from B-14 through MORE THAN TEN YRS OF FOLLOW-UP?? Why re invent the wheel? Why not follow this group for 10 yrs, then 15 yrs, and heck let's have the 20 yr data! They didn't need to recruit and start again.

You are simply hypothesizing why they did a brand new study.

IMO - ALL PATIENTS taking these medications should be tracked as described for 5, 10, 15 and 20+ years of data.  It is frustrating that Tamoxifen was approved in I think 1977!!!  How irresponsible to keep restarting and tracking patients and loosing VALUABLE TIME AND DATA for new patients.  Probably not feasible to back to capture a paper trail of old patient records BUT hospitals were capturing electronic patient records in the mid-1980's. 

Jessica, this is the answer to your question as to why B-14 was not continued:

In the Abstract they say: "A second aim of the B-14 study was to determine whether more than 5 years of tamoxifen administration would provide an advantage greater than that observed when administration of the drug was limited to 5 years. Consequently, women who had completed the initially assigned 5 years of tamoxifen therapy and who were free of disease were rerandomized to either an additional 5 years of tamoxifen therapy or to 5 years of placebo. Interim results at the third of four scheduled analyses demonstrated that continuation of the trial to its intended end point would not result in an advantage for additional tamoxifen therapy. Thus, the statisticians recommended to an independent data-monitoring committee (DMC) that the trial be unblinded and that the treatments be discontinued."

And in the detailed Discussion they say: "After a third interim analysis, it was determined that, even had all of the remaining events necessary for the conduct of a definitive analysis occurred in the placebo group, the log-rank statistic would not have achieved statistical significance. The study was terminated because continuing it until the predefined number of events was reached could not have led to the conclusion that a benefit had been obtained. Moreover, there was concern that continuation of the drug could have been deleterious. At each scheduled interim analysis, a greater number of events were observed in the group of women who continued to take tamoxifen than in those who had received placebo. When the trial was terminated, a nominally statistically significant, or nearly statistically significant, advantage in DFS, distant DFS, and survival was observed in the group of women who received placebo."  

Five Versus More Than Five Years of Tamoxifen for Lymph Node-Negative Breast Cancer: Updated Findings From the National Surgical Adjuvant Breast and Bowel Project B-14 Randomized Trial

So it sounds to me that they terminated the study because they were concerned about continuing to have women take Tamoxifen for the full 10 years because the Tamoxifen women were experiencing a greater number of "events" (recurrences and serious side effects).  The other issue appears to be that due to the sample size (which was significantly smaller than the Atlas trial) they knew that continuing the trial would not change the results, from a statistical standpoint. 

In hindsight it makes sense to suggest that the patients should have continued to be monitored and it makes sense too to say that all patients who take drugs should be tracked.  But this costs money.  Lots of money.  Researchers have to choose which projects to put their money against.  If based on the study data to-date the conclusion was that the continuation of the study would provide no further advancement of knowlegde, then there was no justification to spend the money to continue to track the patients.  Better then to direct the money to a new study.

Jessica...for MOST women who continue taking the Tamoxifen it leads to an advantage.  The point being it is an OPTION.  Think of it this way...there were many sisters who had no side effects from taking the Tamoxifen for 5 years, and while they had early stage breast cancer, they may have had a more aggressive disease.  Some were frightened at the thought of discontinuing it.  Now they have the OPTION of taking it for 5 more years.  Likewise, there are many patients who have a very, very small risk of recurrence and for them, the risk of taking it for another five years might outweigh the benefit.  So physicians and researchers alike were pleased with the results of the study because they concluded that patients CAN take it for 10 years and achieve a "remarkable" benefit. Again, another choice and decision that needs to be made based on one's risk factors, side effects and comfort level.

No.  I just want other readers to know that it's important  to remember that now 10 years of Tamoxifen is an option.  It isn't written in stone that the study concludes that ALL women who complete 5 years of it should continue taking it for 10 years.  Personally, my physician told me when I was diagnosed that I should prepare myself for taking endocrine therapy for 10 years or longer. We were and still in a "wait and see" situation as other endocrine studies evolve.  Regardless, this is STILL great news for most women because it gives them an option.

 Yep!

Yes.  I agree with you.  That's why I think everyone needs to balance the studies and understand what it means to them personally.  I always wonder at what point am I under or over treating myself.  That's why I'm also eager to see the results of the many more endocrine studies that are underway.  I'm in year 3 of taking the Tamoxifen.  I hope in two more years I will have more information to make a decision.  I'm also waiting for the interium results from the SOFT trial which my understanding will be available later this year and probably announced at the December 2013 San Antonio Breast Cancer Symposium.....

Jessica, because the number of participants in the B-14 trial was quite a bit smaller than the Atlas trial, you cannot say that they came to the wrong conclusion when they decided to stop the B-14 trial.  Hindsight is 20/20 but it doesn't change the data that existed at the time. It may very well be true that there was no way that the B-14 trial could ever have reached any different conclusions. 

If you have two groups in a clinical trial, in order for there to be a reportable difference in the results between the the two groups, these results have to be at least 95% statistically significant.  What this means is that if this same trial were to be run 100 times, the same conclusion would be reached in at least 95 of those 100 trials. That's the bar that clinical trials must past so that the medical community is confident that the results aren't just random or the luck of the draw.

The number of people who participate in a trial has a huge impact on how easy, or difficult, it is to achieve a 95% statistically significant result.  Here's an example:

Trial #1:                      Group A  10 Yrs. Tamoxifen           Group B 5 Yrs Tamoxifen

# of Participants                             500                                            500

7 Yr. Results:  # of Recurrences    150                                            122 

7 Yr. Results: # of Deaths                34                                              20  

These 7 year results are 95% statistically signficant, suggesting that 5 years of Tamoxifen is preferable to 10 years, with both fewer recurrences and fewer deaths. If the data continued to be collected for another 3 years, in order for the conclusion to be changed after 10 years, the results would have to be something like the following:

10 Yr. Results: # of Recurrences     160 (+10)                                 190 (+65)

10 Yr. Results: # of Deaths               36 (+2)                                     54 (+34)    

These results are also 95% statistically significant; now they show that the 10 year group has fewer recurrences and deaths.  But could this have really happened? With only 500 people in each group (and fewer than 400 who had not yet had a recurrence), could 3 more years of results possibly been skewed this way?  Not very likely. The results certainly might have started to skew towards the 10 year group, but it's unlikely that the results would ever have become statistically significant in favor of the 10 year group. And without statistically significant results, the likely conclusion would have been that 10 years and 5 years of Tamoxifen provide equal benefit. (By the way, this sample size is about what B-14 actually had for this part of the test.)

But here's how a larger sample size (such as found in the Atlas study) could make a difference. If we look at an identical example, but with a larger participant group, you can see that the possibility exists that the results could flip over the last 3 years.

Trial #2:                      Group Y  10 Yrs. Tamoxifen           Group Z 5 Yrs Tamoxifen

# of Participants                            2500                                          2500

7 Yr. Results:  # of Recurrences     686                                            625 

7 Yr. Results: # of Deaths               129                                            100  

Again, these 7 year results are 95% statistically significant, showing fewer recurrences and deaths for the 5 yr. Tamoxifen group. 

10 Yr. Results: # of Recurrences    730 (+44)                                  794 (+169)

10 Yr. Results: # of Deaths             142 (+13)                                  176 (+76)  

Again we have 95% statistically signficant results, now showing that the 10 year Tamoxifen group has fewer recurrences and deaths.  With 2,500 women in each of the two groups, these results could certainly happen over 3 years.  

So the question is, why aren't all studies done with large samples?  Cost.  Ability to recruit and retain participants.  And because it's not always necessary.  If there is a clear cut difference, then a smaller sample size might be able to show this very well. So until you get the results, you don't know if the number of participants was okay or if there were too few.  Those who ran the B-14 trial wouldn't have had any idea that their groups were too small, until Atlas was released with different results. 

Sorry if this is boring or too much detail.  I'm a research/numbers geek, so I find it interesting to work out these types of examples.  Hopefully it's of value to a few people!

Hi 

I also wrote on another site today because I didn't know about this page.

I have been on Femara since January 2010 and am doing well, I dont want to come off of it as I really think it works.  My oncologist told me my cancer was fed by my hormones and that going on Femara would reduce the production of estragen by 90%.  I am hoping that when my 5 years are up the oncologist will keep me on Femara for at least another 5 years.  I really don't have many problems with the drug, a few hot flashes and hair loss but I am more than willing to stay on the Femara if it keeps me around to see the grandkids grow up.  

My question to you all is has ANYONE out there been on Femara for longer than the 5 years.  If so please reply.

I was diagnosed in June 2009 had lumpectomy and had 7 nodes which were pos.  This sounds bad but so far no sign or recurrance and I think if I come off the Femara the cancer will come back

Let me know what you all think

Hugs and thanks to you all

Nannajean

nannajean...Glad to hear you're doing well.  While the good news from the Atlas study pertains exclusively to Tamoxifen, the even better news is that there are several more endocrine studies under way concerning AIs, as well as, Tamoxifen and AIs together.  You might want to look at the professional version of the 2012 NCCN breast cancer treatment guidelines pages 94-98.  Those pages discuss all of the ongoing endocrine trials.  Since you were diagnosed in 2010, like me, we have the benefit of time to see, how in the next few years, those other studies unfold.  IMHO opinion, for patients like yourself, whose risk of recurrence is greater than 10%, and have few or no side effects, will likely have an option of doing endocrine therapy for 10 years...or perhaps even longer.....

This is truly fascinating. Thanks so much for all of your hard work and research. For newbies like me with a zillion questions about AH's, this is extremely valuable information! You guys rock!

PS Now I get why a noted surgeon mentioned once  that statistically, they like to see at least 3,000 people in a study...

Saw my oncologist last week, he indicated that it is likely that once I finish two and half years of Tamoxifen that he most likely will recommend five full years of an AI depending on research published between now and then. I already have osteopenia so we'll have to keep a close eye on my bones though. 

Dear Beezie. I am currently 12years post mastectomy. Had 5-7 years of Letrozole in a d/b trial after 2 series of different chemos, the last one was Taxotere as I had 12 pos l/n.

Also have lymphodema following axilla rad.



I recently took a years break from the letrozole (unbenownst to my doctors....had been allowed to carry it on after the trial at my request. Have you seen any research evidence re either of these points please? 1/ memory loss, vertigo etc following long term use

Or 2/ problems when recommencing after a years gap in women in their 60s?



Thank you

Beesie's thinking intrigues me too.

After all, had I taken tamoxifen for an extended period, I would have been counted as someone who "benefitted" from extended use of tamoxifen.

If I had taken trastuzumab, I would still be counted as someone who "benefitted" from taking it, too.

(See my signature.)

To add to the discussion about extended use of tamoxifen, benefit/risk, etc.:

Breast density identification for cancer risk

http://breast-cancer-research.com/content/14/4/r114

Breast density California Law

http://www.cmanet.org/news/detail/?article=new-breast-density-notification-law-goes-into

More recent study by the Karolinska Institute on breast density in regard to tamoxifen usage

http://ki.se/ki/jsp/polopoly.jsp?l=en&d=130&a=162862&newsdep=130 

On a personal basis, at age 51 prior to any treatment, my breasts were very dense. Upon completion of chemotherapy and rads, my breasts were very dense, just prior to starting tamoxifen. After just 3 months of being on the standard dose of tamoxifen, my mammogram showed my breasts were almost entirely clear of density. This possibly meant that I was an exceptionally good tamoxifen metabolizer. I have never been tested to know if that is true or false. I also wonder if being ER 95% was especially meaningful in terms of the effect.

A.A.

P.S. At my checkup last fall my bone density came back extremely good, pretty much off the scale. I just had an echocardiogram, and prior to tx in 2002 my echo was 76 and it is now 70 despite Adriamycin but with no trastuzumab.