San Antonio Breast Cancer Symposium 2012

http://www.webmd.com/breast-cancer/news/20090825/tamoxifen-rare-second-breast-cancer-risk?page=2

"Li counts increased risk of stroke and endometrial cancer among tamoxifen's known risks, and he says ER-negative cancer may be another risk. 

But Li isn't calling for any change in how tamoxifen is used in breast cancer patients, or for taking tamoxifen for less than five years, because overall, the benefits still win out.

"The randomized trials looking at tamoxifen have very convincingly shown that full benefit of the drug is only obtained when it's used for five years," Li says. "I don't think they should change the recommendation that women should use it for the full five years."

Li also emphasizes that ER-negative breast cancers are rare, and that the study wasn't designed to show a woman's absolute risk of developing an ER-negative breast cancer.

"This is a relatively rare type of second cancer. In our study, only 25% were of this type," Li says. "So for the vast majority of cancers, [tamoxifen] is lowering the risk of second cancers. But for the smaller subset, this 25%, it's increasing the risk."

The study doesn't prove that tamoxifen caused any cancers, though Li's team weighed many other factors in analyzing the data.

Li and colleagues aren't sure how tamoxifen might raise ER-negative breast cancer risk, but they speculate that targeting ER-positive cells may allow ER-negative cells to take center stage. The researchers plan to study that further and to check to see if the findings also apply to another class of estrogen-related breast cancer drugs called aromatase inhibitors...."

I think what Dr. Li's takeaway message regarding his research is that in this "observational study" he and his colleagues noticed this increased risk of ER negative breast cancers from long term use of Tamoxifen and until it is studied further, he thought that it should be mentioned among the risks....  Observational studies do NOT hold the same "weight" as clinical trials....so there really is no contradiction...However, I DO think he is correct that it should be mentioned AND studied further.....

Okay.  I finally got the study and have read it several times. From the Discussion section:

"Previous trials have shown that, for women with ER-Positive early breast cancer, 5 years of adjuvant tamoxifen substantially reduces recurrence rates throughout the first 10 years after diagnosis and substantially reduces breast cancer mortality throughout the first 15 years.  Thus, the effects of 5 years of treatment with tamoxifen on annual rates of mortality persist for at least a decade after treatment ends.  Because of this carryover benefit after only 5 years of tamoxifen, it was already recognized when ATLAS began that there could well be little additional benefit during the first few years of additional treatment, even if worthwhile benefit would emerge later.  WITH AN AVERAGE OF 7.6 WOMAN-YEARS OF FURTHER FOLLOW-UP AFTER ENTRY AT 5 YEARS, THE FINDINGS THUS FAR AVAILABLE CONFORM WITH THESE EXPECTATIONS.  ATLAS HAS NOW SHOWN THAT COMPARED WITH STOPPING AFTER ONLY 5 YEARS OF TAMOXIFEN, CONTINUING FOR ANOTHER 5 YEARS (TO 10 YEARS) PROVIDES FURTHER PROTECTION AGAINST RECURRENCE AND BREAST CANCER MORTALITY, PARTICULARLY AFTER REACHING 10 YEARS."

Figure 3 contains a graph showing treatment allocation.  It shows that at the 7th year mark of taking Tamoxifen, the number of recurrences begins to rise for those NOT having taken tamoxifen for two years.  That number continues to increase consistantly out to the 15 year mark.  So while the difference was small at first, the population that continued on the Tamoxifen began reaping rewards at the 7th year that continued into the 15th year.

So, regarding Beesie's hypothesis that taking tamoxifen for 5 years, followed by a break and then another 5 years, pushing out the potential carryover effect, doesn't seem to appear to be a good idea, because the benefit gained continuing on the tamoxifen during the uninterrupted second five years begins at the 7th year and continues, until it becomes a "remarkable" difference after the 14th year.  Earlier data suggested that between the 5th and 10th years, there was no difference.  But Atlas proves that while small, the difference does in fact occur and continues without interruption.  So, if one chose to not continue after 5 years, I THINK they can never recoup that difference.

One thing that disappointed me about the study was that the patients were referred to as "early stage"  but they weren't broken down by the grade.  The good news was that we know their ages, nodal status, tumor diameter, menopausal status, what kind of surgery they received and whether or not they had a hysterectomy.  The majority of the women chosen for the trial were POSTmenopausal.  I guess the reason for that is because tamoxifen was in use longer at the time.

So, what did I learn from reading the study?  While the risk of recurrence was LOWER during the second 5 years (meaning...you got the most bang for the buck during the first five years when you were more likely to recur),  the "main effects on recurrence and particularly, on breast cancer mortality became apparent only during the second decade after diagnosis."  Meaning...whether due to the carryover of the first five years or continuation of the second uninterrupted 5 years of tamoxifen, you reduced your risk by taking the tamoxifen, even though through the 7th year of taking the tamoxifen, the relative risk of recurrence vs. the benefit of therapy was small.  HOWEVER, as you moved away from the 7th year of uninterrupted use of Tamoxifen, the benefits begin to widen over those who declined taking it past 5 years. A 1% difference at 7 years becomes at 15 years, a absolute difference between the two groups at over 3%....

So, what do I think?  I think if we had more information, such as grade or genomic information about these subjects tumors it would have helped clinicians more in guiding treatment.  Unfortunately, back when this study started, there was no Mammaprint or Oncotype DX test.  So, a patient must decide based on the aggressiveness of their tumor if the absolute risk reduction benefit of 3% is worth the risk.  Keeping this study in mind, we don't know if switching to an AI after a few years on Tamoxifen or even just 5 years of an AI for those women who are POST menopausal would cancel out the benefit of 10 years of Tamoxifen....

I welcome the number of other endocrine studies that are currently being done to find the answers to those questions.

In the meantime, I'm glad patients now have more options.