Taking aromatase inhibitors longer than 5 years?


Question from Speechpro55: Are there any updates on the efficacy of continuing aromatase inhibitors past the 5-year mark?
Answers - Ruth Oratz, M.D., F.A.C.P. There was a great deal of discussion at this conference about hormonal therapy of estrogen-receptor-positive breast cancer in postmenopausal women. All of the major clinical trials looking at the use of aromatase inhibitors in this population were updated at San Antonio this year in a meta-analysis of all studies, using aromatase inhibitors either as first-line hormonal therapy for 5 years or in studies in which patients received tamoxifen first and then switched to an aromatase inhibitor. In all of these trials, there was a benefit for the use of aromatase inhibitors. The benefit of aromatase inhibitors compared to tamoxifen is modest. The benefit is between a 2 and 4% decrease in breast cancer recurrence, much of which relates to a decrease in either local recurrence in the breast or in the incidence of contralateral breast cancer. There was less of an impact of aromatase inhibitor use on distant recurrence for metastases. There was no significant survival benefit to the use of aromatase inhibitors for any duration of treatment when compared to tamoxifen. The question of duration of hormonal therapy remains unanswered. In only one clinical trial do we have information about more prolonged treatments with aromatase inhibitors, that is beyond 5 years, and it is unclear if prolonged therapy has a significant benefit over 5 years of treatment. There is some concern and difficulty in interpreting the results of these clinical trials because in most of the studies, patients were able to cross over and receive treatment with aromatase inhibitors if they had been on tamoxifen alone, or to continue treatment beyond the set duration of time. So it's difficult to interpret this data. I'm not sure that we're going to have a clear-cut answer on whether or not prolonging therapy beyond 5 years of hormonal treatment truly is beneficial or not. We did not see that information emerge from any of the presentations at San Antonio this year.
Ruth Oratz, M.D., F.A.C.P. I would also add there was a lot of discussion about aromatase inhibitors being superior to tamoxifen. I really want to emphasize (and this is my own personal viewpoint but I think shared by many others) that the benefits are modest. The side effects from these aromatase inhibitors are significant and not inconsequential. And although this was mentioned only really in one presentation, some of the difference between response to aromatase inhibitors and tamoxifen may be accounted for by the fact that perhaps between 7 and 10% of individuals taking tamoxifen do not actually derive the maximum clinical benefits from tamoxifen. The reason for this is that tamoxifen must be activated by enzymes in the liver to its active metabolite endoxifen, and perhaps up to 10% of individuals do not have the enzyme that activates tamoxifen. Also, some medications -- in particular, antidepressants -- may interfere with the activation of tamoxifen. Many patients taking tamoxifen are also on these medications, and these include Paxil (chemical name: paroxetine), Zoloft (chemical name: sertraline), Wellbutrin (chemical name: bupropion HCI), all the common anti-depressants. Perhaps some of the differences we see between aromatase inhibitors and tamoxifen are in fact related either to problems with tamoxifen metabolism or interference with tamoxifen activation by other medications. Both tamoxifen and aromatase inhibitors are effective, active hormonal therapies for women who have estrogen-receptor-positive breast cancer. The choice of which agent is best for each individual patient should be discussed by each woman and her physician, taking into account factors such as other medications that she may be on, and perhaps even the consideration of testing for the presence of the enzymes that activate tamoxifen.

Editor's Note: If you are taking tamoxifen, talk to your doctor about alternative antidepressants. For more information, please visit the Breastcancer.org Tamoxifen page.
Carol Kaplan It's important to note that the standard of care at this time for aromatase inhibitor therapy is an aromatase inhibitor treatment duration of no more than 5 years.
Ruth Oratz, M.D., F.A.C.P. Either 5 years total tamoxifen plus aromatase inhibitor, or 5 years of the aromatase inhibitor, or 5 years of tamoxifen followed by 5 years of aromatase inhibitor. They're all effective; whether one is better than the other remains to be seen.

On Wednesday, December 17, 2008, our Ask-the-Expert Online Conference was called Updates from the 2008 San Antonio Breast Cancer SymposiumRuth Oratz, M.D., F.A.C.P. and Carol Kaplan, M.D. answered your questions about the latest updates on breast cancer risk, screening techniques, treatment options, and more.

The materials presented in these conferences do not necessarily reflect the views of Breastcancer.org. A qualified healthcare professional should be consulted before using any therapeutic product or regimen discussed. All readers should verify all information and data before employing any therapies described here.

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