Q&A

On Cancer: Breast Cancer Specialist Clifford Hudis Discusses Potential Benefits of Extended Tamoxifen Therapy

By Esther Napolitano, BS, Science Writer/Editor  |  Wednesday, December 5, 2012
Pictured: Cliff Hudis
Video

Memorial Sloan Kettering breast cancer specialist Clifford Hudis discusses the results of an international clinical trial that has the potential to change current treatment practice for certain women with breast cancer.

(02:00)

New, potentially practice-changing research is shedding light on the long-term benefits of estrogen-blocking tamoxifen therapy in women with early-stage breast cancer whose disease is also estrogen-receptor (ER) positive. The findings of a large study, which involved more than 6,800 women with ER-positive disease, may lead doctors to advise such patients to continue taking tamoxifen beyond the current recommendation of five years. 

The collaborative international study, known as ATLAS, was led by researchers at the University of Oxford and was presented today at the San Antonio Breast Cancer Symposium – an annual conference where the latest information on breast cancer research and treatment is shared among thousands of physicians and scientists in the field. The research has also been published today in The Lancet.

To better understand the study’s findings and clinical implications, we spoke with medical oncologist Clifford A. Hudis, Chief of the Breast Cancer Medicine Service at Memorial Sloan Kettering and President-Elect of the American Society of Clinical Oncology.

What is tamoxifen?

Breast cancer cells that have receptors for the hormone estrogen are called estrogen-receptor (ER) positive and are more likely to respond to therapy with anti-estrogen medications such as tamoxifen – an FDA-approved drug that acts by blocking estrogen from feeding estrogen-dependent cancer cells.

The drug is known to greatly reduce the risk of a breast cancer returning, also known as recurrence, as well as the risk of death from the disease. Tamoxifen also has the added benefit of preventing a new breast cancer from developing and may treat or prevent osteoporosis – a common condition among older women in which bones become more fragile and more likely to fracture.

What is the current standard of care for women with early-stage ER-positive breast cancer?

The current recommendation for women who have already been treated with surgery and/or radiation therapy calls for five years of follow-up treatment with tamoxifen. Up until now, it was unclear how extending treatment with tamoxifen from five years to ten years affected patient outcomes in the decades after diagnosis.

What did the ATLAS study find?

Women in the study had approximately five years of tamoxifen therapy after their initial surgery and/or radiation therapy. They were randomly assigned to either continue the therapy for another five years or to stop at year five.

Researchers followed the women over time and found that those who continued to take tamoxifen for a total of ten years were further protected against breast cancer recurrence and, particularly during the second decade, death from breast cancer. An additional analysis projected that breast cancer deaths would be reduced by at least one-third 15 years after diagnosis among women who take tamoxifen for a total of ten years.

Are there any added risks to taking tamoxifen for a longer period of time?

There is a small risk of uterine cancer among women who take tamoxifen for five years — about one in 500. The study did find that postmenopausal women over age 50 may have a slightly higher risk of developing uterine cancer if they continue treatment for an additional five years. On the other hand, there was no apparent higher risk of uterine cancer among premenopausal women who continued to take the drug.

Do you think the results of this study will change the way breast cancer is managed?

The observations gleaned from this important study do support extending the duration of tamoxifen beyond the current five-year recommendation. However, I believe longer follow-up and more-detailed analysis of ATLAS is necessary to more reliably assess the apparently substantial decrease in breast cancer deaths in the second decade after diagnosis and possibly change how we manage patients. 

It’s worth mentioning that these findings could have the greatest impact on younger, premenopausal women with ER-positive breast cancer who are at higher risk of recurrence and currently have no alternative treatment options after the first five years of tamoxifen therapy — whereas postmenopausal women can be offered another class of drugs called aromatase inhibitors, which interferes with the production of estrogen.

Women with breast cancer should discuss with their doctor the benefits and risks of tamoxifen and how its use might affect their own health.

Comments

We were told Tamoxifen for five years only. I still believe if the protocol had continued, we would not be dealing with bone and peritoneal metastasis. Thank you for your work and recommendations and only wish we had known.
Dr. Babcock
Austria

Does this research have any bearing on the use of Arimidex for more than five years as well?

Only indirectly, according to Dr. Hudis. If longer hormone therapy is better using tamoxifen, it may be true for anastrazole (Arimidex) as well. But he says that we await studies on this specific question. Thanks for your comment!

I am currently on Arimidex therapy following masectomy in 2010. How does Tamoxifen therapy compare with Arimidex?
What should patients do, if anything.

According to Dr. Hudis, patients on anastrazole (Arimidex) should not generally do anything with this new data as it pertains to tamoxifen. But they should discuss these results with their doctor, as it could mean that longer therapy with anastrozole is similarly more effective. There are studies pending that will address this question. Thank you for your comment!

You mention surgery and/or radiation therapy. Should those women who have also undergone chemotherapy remain on Tamoxifen for 5 years?

Thank you for your comment! Dr. Hudis says that this study looked at the duration of tamoxifen independent of whether or not the patients had radiation therapy (some did) or chemotherapy (some did).

I would like the conversation to include: Women in their 60's who should be "post" menopausal, but who still have Estradiol levels that keep them in the menopausal category, currently on Tamoxifen -- can one take Tamoxifen for 10 years, and then switch to an aramotase inhibitor for another 10 years (or beyond)? The bigger question is: Is it advantageous for women who have ER+ cancer to take some sort of estrogen blocker FOR THE REMAINDER OF THEIR LIVES? Based on the new research that asserts an additional 5 yrs on Tamoxifen, my sense is that further research will conclude that remaining on a blocker for a woman's lifespan to be the new protocol. So, until then, where does the current protocol leave current patients? Can a woman request to remain on a blocker past current protocol?

We spoke to Dr. Hudis, and he explained that the data in this study address only the question of five versus ten years of tamoxifen, independent of menopausal status. Thank you for your comment!

I was on Arimidex for 5 years ending in 2009. Should I restart taking Arimidex or Tamoxifen again.

Thank you for your comment. We are unable to answer personal medical questions on our blog, and we recommend that you discuss this question with your physician.

Wow, what do I do. I had two bilateral stage 1 cancers that were .7 cm
tumors each, one in the right breast and one in the left breast. The first
cancer was found in 1970 and the second was found in the other breast
in 1971. As I said, both were stage one cancers and both were about
.7cm small, both under 1 cm. I had radiation in 1970 on the right breast
and in 1971 had double mastectomies when the second cancer
in the other breast were found. I am ER positive. I did not have
chemo. They did not advise it and I took tamoxifen for 5 years.
I am at 13 years out. I have also had both my ovaries and my uterus
removed as a preventive measure. They did not adivise an
aromatose inhibitor for me. I am 63 years old. Do I now
take tamoxifen. Your thoughts would be appreciated, I am cofused
as to what to do.

Thanks for your comment. Unfortunately, we can't answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call 800-525-2225.

Although I would agree with the insightful commentary of my colleague Cliff Hudis, above, that the new extended findings of the ATLAS trial are indeed highly intriguing, and promising of potential practice-changing impact, there are nonetheless some open questions yet to be resolved, especially in the light of previous trials having failed to detect clinically significant benefit from extended tamoxifen therapy past 5 years. In fact in the NSABP B-14 trial, a slight advantage was observed in patients who discontinued tamoxifen relative to those who continued to receive it, through 7 years after reassignment of tamoxifen-treated patients to either placebo or continued tamoxifen therapy, with DFS = 82%, RFS = 94%, and OS = 94% in the placebo arm, compared to DFS = 78%, RFS = 92%, OS = 91% in the continued tamoxifen arm, and that estimates of outcome still favored placebo over continued tamoxifen therapy.

In addition, the randomized Scottish Cancer Trials Breast Group [Stewart HJ, Forrest AP, Everington D, McDonald CC, Dewar JA, Hawkins RA, et al. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. Br J Cancer 1996; 74:297–9.] found in a preliminary analysis of outcome in 342 patients at a median follow-up of 6 years that a clinically meaningful gain in disease control from continuing adjuvant tamoxifen beyond 5 years was unlikely, with a suggestion that therapy for longer than 5 years may increase the risk of endometrial carcinoma. And an early (1996) ECOG trial similarly found that the survival difference for the extended tamoxifen therapy subgroup was not statistically significant over standard 5-years of tamoxifen.

Finally, there is to this researcher some concern over sharp emergent-benefit threshold: thus, the recurrence and mortality rates were in fact similar in the two study groups for the years between years 5 through 9 of tamoxifen therapy, diverging significantly only after year 10 women where we suddenly there emerges a 25% lower rate of recurrence and a 29% lower breast cancer mortality compared to women who termination tamoxifen after 5 years, and although this is in principle not impossible, the cutover nonetheless is somewhat perplexing, with no progressive benefit accruing until that threshold. And note that by the time accrual completed for the trial, most subjects were postmenopausal, so implications for premenopausal populations are less clear. If these ATLAS trial results are most robust for postmenopausal populations, then that raises the question of whether extended tamoxifen (past 5 years) is motivated in clear benefit over a switch to AI therapy past 5 years of initial tamoxifen therapy, an option many clinicians may increasingly entertain.

Constantine Kaniklidis
European Association for Cancer Research (EACR)
Medical Research Director, No Surrender Breast Cancer Foundation (NSBCF)

I read your research with great interest. I am on the 4th year of tamoxifen. I will certainly discuss this with my consultant.

I had surgery, chemo (dose density adriamycin, cytoxin, taxol) followed by radiation in 2003. After a failed and excruciatingly painful 7-week period on arimidex, I successfully completed 5 years of tamoxifen 2004-2009. I then tried aromisin and went off after only 10 days because of the same horrible joint pain and spasms -- I cannot tolerate aromatase inhibitors.
(1) Should women who have also had chemo be candidates for tamoxifen for 10 years instead of 5?
(2) Would there be any benefit to taking tamoxifen for another 5 years with such a long break since I finished my first round in March 2009?
i am now 59 and have been postmenopausal since 2003 just prior to starting chemo. Thank you.

We are unable to answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call our Physician Referral Service at 800-525-2225. Thanks for your comment!

I am 65 years old. I had my surgery( stage 2 ) followed by chemo in 2002. I took Tamoxifin for 5 year and am now on my 5th year of taking Aromatase inhibitor, Femara. Is there any benifit of taking another 5 years of Tamoxifin now ?

Thanks for your comment! We are unable to answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call our Physician Referral Service at 800-525-2225.

.........excellent article, please keep the information flowing to the patients and their families. Thank you all for the great job you are doing.

Very interesting findings but I see no mention of increased risk of severe osteoporosis following five years on Tamoxifen. What, if any, information is available on that subject?

We spoke to Dr. Hudis, and he said that Tamoxifen helps prevent osteoporosis, whereas aromatase inhibitors promote this problem.

what about increased risk of stroke
when taken 5years stroke risk increase
1 in a hundred
what is the risk if taken for ten years?

Dr. Hudis says that the reported ten-year stroke risk was the same as the risk for five years. Thank you for your comment!

Would this also include Raloxifene (marketed as Evista by Eli Lilly and Company) treatment for LCIS?

Thank you for your comment! This particular study was focused on tamoxifen.

what about cataract and eye damage risk?
what are the percent risk of stroke for the 5 year and the 10 year
thank you

We spoke with Dr. Hudis, and he said that the risk of stroke did not rise significantly from year five to ten, nor did the ocular toxicities. These small risks must, of course, be balanced against an individual's potential gain through a careful discussion with his or her physician. Thank you for your comment!

What about MALE breast cancer patients (like me) who have to take tamoxifen ?

Hi, we spoke to Dr. Hudis and he said that we can't be certain, but we believe these results apply equally well to men. Thanks for your comment.

Congratulations for the nice article.But you did not stress much about other Tomaxifen induced problems in your study.Please do report us.

Thank you for your comment! We encourage you to look at many of the other comments on this post. Dr. Hudis has addressed questions about osteoporosis, stroke, and damage to the eye. If you have a question about a particular potential side effect, please let us know. Here is the link to the study abstract as well: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961963-1/abstract.

2 surgies - margins were not clear - breast had to be removed - insisted on removal of good breast - chemo - femara-haven't been comfortable since 2009-sometimes I wonder!!!!!!!!

Please tell people to change life Style!

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