From the Clinicaloptions website
http://www.clinicaloptions.com/Oncol...ought/BC3.aspx
For How Long Should Tamoxifen Be Offered to Patients With Early-Stage, Endocrine-Sensitive Breast Cancer?
William J. gradishar, MD, FACP -
1/17/2013
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Numerous interesting presentations were made at the
2012 San Antonio Breast Cancer meeting, including an update from the ATLAS trial on the pros and cons of extending tamoxifen therapy beyond 5 years.
For the last decade, 5 years of adjuvant endocrine therapy with tamoxifen has been viewed as a standard treatment duration period for patients with early-stage,
endocrine-sensitive breast cancer. Before that time, there was a question as to how long would be optimal, and in fact, a number of studies addressed that issue. A
pivotal trial from the NSABP (B14) compared 10 years of tamoxifen to 5 years of tamoxifen in patients with early-stage, endocrine-sensitive breast cancer. In that trial, investigators found that durations beyond 5 years resulted in a worse PFS, which was statistically significant and a trend suggesting that OS was inferior. The
National Cancer Institute issued an alert to oncologists indicating that 5 years of therapy should be viewed as the optimal duration.
Although there were other studies that had discordant results, the NSABP study was very influential and most oncologists currently use 5 years as their own standard. At the time, there were also other trials that had not yet reported and that kept the question alive, including the ATLAS and
ATTOM trials, which looked at longer durations of therapy compared with 5 years of therapy. At the 2012 San Antonio Breast Cancer meeting, the issue of duration was once again addressed as investigators from the
ATLAS trial reported findings from more than 6000 patients with estrogen receptor–positive disease who received 5 years of tamoxifen, after which they were randomly allocated in a one-to-one fashion to stop tamoxifen or continue tamoxifen for another 5 years. The study tracked all recurrences, second cancers and deaths, and toxicities, including endometrial cancer. This is a trial that, in its totality, had in excess of 12,000 patients. The trial was started at a time when patients with estrogen receptor–negative disease were also included, since it was unclear whether or not there might be a benefit to be conferred to such patients. We now know that patients with estrogen receptor–negative disease gain little benefit from antihormonal therapy in general and
tamoxifen in particular.
In the ATLAS trial reported at San Antonio and subsequently
published in Lancet, there was an improvement in outcome, with statistically fewer recurrences (18.0% vs 20.8%) and fewer deaths from breast cancer (9.7% vs 11.6%) in patients who received 10 years vs 5 years tamoxifen therapy. Interestingly, the impact of extended tamoxifen use was not noted in Years 4-9 but rather in the years beyond 10 years of therapy. And it may be that the carryover effect from the first 5 years of therapy was still dominant in the years immediately after the first 5-year period of tamoxifen therapy. In the ATLAS trial, patients who received tamoxifen for 10 years had a greater reduction in risk of progression, overall, in years beyond 10 years of treatment. The cumulative risk for endometrial cancers during Years 5-14 was 3.1%, with a mortality associated with endometrial cancer of 0.4%. This was somewhat higher than what was noted in patients receiving only 5 years of therapy (cumulative risk: 1.6%; mortality: 0.2%), but the mortality risk was only modestly increased.
So, how are we to interpret these data? My own view is that this is intriguing, but the world has changed significantly since this trial was initiated. Certainly, for postmenopausal women, aromatase inhibitors are largely physicians’ treatment of choice now for women with hormone-sensitive breast cancer. If tamoxifen is used, it tends to be used in sequence with an aromatase inhibitor as a result of multiple large, randomized trials from around the world demonstrating that the integration of aromatase inhibitors is incrementally better than tamoxifen. However, for premenopausal women, who remain at risk because of tumor characteristics, the notion of continuing tamoxifen beyond 5 years is an option based on these data.
In addition, because the impact of long durations of tamoxifen (10 years) is seen only after 10 years of therapy is complete, it raises the issue of whether or not one could conceivably consider a sandwich approach in women who are postmenopausal: tamoxifen followed by an aromatase inhibitor and then, at a later time, tamoxifen again. These sorts of hypothetical situations need to be addressed by clinical trials before they can be suggested as optimal ways to approach tamoxifen therapy.
For now, the ATLAS trial is an important one, but there will be additional information forthcoming, including updates from the ATTOM trial, and we also anticipate that next year the
Oxford overview analysis of randomized trials of tamoxifen will be updated once again and will include data from ATLAS, ATTOM, and other randomized trials to give more clarity to the question of whether 10 years of therapy is indeed superior to 5 years of tamoxifen treatment.
So, do these new data affect how you will use tamoxifen? Is it too early to change patient management practices or is it about time? Let us know.
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Dear colleagues, what about agonistic property of tamoxifen after 2year using ...
Lali Rogoniya - 2/10/2013
I am sure continuing Tamoxifen beyond 5 years is a logical option in pre-menopausal women with positive status of estrogen/progesterone. Maybe it is worthwhile to switch to sandwitch mode after the woman has reached the post menopausal status.
Dr H L Kapoor - 2/5/2013
In my opinion it could be an option for Luminal A patients, with a higher title of ER, and why not for premenopausal women in high risk of recurrence.
Ludwing Bacon - 2/4/2013
While this is an interesting question, as it is known to everybody the clinical scenario seems to have multiple factors that come into play to address how to better move forward. However, it may be worthwhile to wait until additional few months for more concrete answers when updated results of other clinical trials are up.
Doctor "T" - 1/29/2013
Why dont we show these results to our patients and let them decide? For Node negative 5 years could be enough.
rahal - 1/28/2013
For premenopausal women this results would be an option for extended adjuvant hormonal therapy, especially for very young and high risk breast cancer patients. It is also can be an option for postmenopausal patients who had severe adverse effects with AI. Gynecologic complications are very important, but we have very few knowladge from ATLAS trial.
Nilüfer Güler - 1/27/2013
I think 10 years of tamoxifen in premenopausal, high risk, like node pos, is a reasonable option.
n khoury - 1/23/2013
Too early to change the practice.
MButt - 1/23/2013
For premenopausal women this would be beneficial. Sandwich treatment can be an option for post menopausal women alternating AIs with Tamoxifen thereby reducing the side effects.
Beena Devi - 1/22/2013
I feel 10 years or even longer (as I believe future studies may find) for the continual use of tamoxifen.
Kerry Reed - 1/21/2013 
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