Archive for February, 2013

From the Director

ellycohenNov2008Best

Elly Cohen, Ph.D., BCT Director

When my mother was diagnosed with metastatic breast cancer in 1978, her doctor told her about tamoxifen, a drug that had been recently approved for women with estrogen sensitive tumors. Unfortunately, her tumor was ER-negative and, despite chemotherapy, she died less than a year later. Twenty years later, when I was diagnosed with stage 1, ER-positive breast cancer, tamoxifen was being used for early-stage patients too. That’s because in 1986 a clinical trial showed that tamoxifen lowered the risk of recurrence in patients like me. The studies also had showed that five years of tamoxifen provided the most benefit.

So, I was surprised and confused when a large study presented at the San Antonio Breast Cancer Symposium found that it was better for women to take 10 years of tamoxifen than five. How could the findings from the ATLAS study be so different from the evidence upon which my treatment was based?

That’s why we decided to focus this issue of our newsletter on the ATLAS trial. We wanted not only to clarify the findings, but also to give an example of how research is a continuous process of learning and improvement.

There is little doubt that over the next decade clinical trials now underway will tell us more about how to best use hormone therapies to treat breast cancer. We may also identify drugs that can get tumors to overcome resistance to hormone therapy, so that these therapies can be used longer. You can see all of the hormone therapy trials we have listed on BCT here. We encourage you to forward that link on to anyone you know who might be interested in these trials.

And if you haven’t yet done so, “like” us on Facebook. Each week, we post every new trial we have listed on BCT.

February 28, 2013 at 10:59 pm 1 comment

ATLAS: When Research Changes Practice

Tamoxifen

ATLAS put ten years of Tamoxifen to the test.

Each year before the San Antonio Breast Cancer Symposium begins, there is always a buzz about what the big news will be. There is little doubt that in 2012 the findings that garnered the most attention were from the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial , which showed that taking the hormone therapy tamoxifen for 10 years was more effective than taking it for five, the currently recommended treatment.

To understand why this was significant, we need go back to 1995. That’s when the NSABP B-14 study, a U.S. trial comparing 10 years of tamoxifen to five years of the drug, was stopped early because the trial data suggested that not only was 10 years not better— it might even be worse. (More recurrences were seen among the women taking tamoxifen longer.) From that point on, there was no question, at least in the U.S., that tamoxifen should be taken for five years—and no longer.

Outside the U.S., however, questions remained. And in 1996, convinced that the issue was not settled, the Clinical Trial Service Unit (CTSU) at the University of Oxford launched ATLAS, an international trial that enrolled 6,846 women with ER-positive breast cancer who had already taken tamoxifen for five years. Half of the women were randomly assigned to take tamoxifen for five more years. The other half stopped treatment.

As the ATLAS trial group reported at San Antonio and in the Lancet, after about eight years of follow-up, 1,328 breast cancer recurrences and 728 deaths had occurred among all the women in the study. In years five to nine after diagnosis, the number of recurrences and deaths didn’t really differ between the two groups. But that changed once the women were about 10 years out from their diagnosis. At that point, the women who had stayed on tamoxifen were 25 percent less likely to have their cancer recur and 29 percent less likely to die of breast cancer than were the women who had stopped at five. In sum: The risk of dying from breast cancer five to 14 years after diagnosis was 12.2 percent among those who continued on tamoxifen compared with 15 percent among those who stopped — an absolute gain of 2.8 percent, with the greatest benefit 10-14 years after diagnosis.

Richard-Gray

Dr. Richard Gray

To learn more about the ATLAS trial, BCT spoke with Dr. Richard Gray, the professor of medical statistics at the University of Oxford who presented the findings at San Antonio on behalf of the ATLAS group.

Q: Why did the ATLAS group think that it might be beneficial for women to stay on tamoxifen longer?

A: We didn’t believe there was convincing evidence that taking tamoxifen for longer than five years was worse. The NSABP study did report worse outcome, but that was based on small numbers (1000 patients), and the difference was not extreme, so there was the possibility it could be a chance finding. There is also the complication that if women take tamoxifen for five years and then stop, it will continue to reduce recurrences over the next five years. So if you are comparing 10 years with 5 years, you don’t expect to see benefit for the first few years because of that carryover effect.

Q:  And after 10 years, tamoxifen did?

Yes.  What we found is that you can’t beat that carryover effect for the first five years. [Years five through nine after diagnosis.] But after that you do start seeing the benefit.

Q: Was it difficult to enroll women in the ATLAS trial?

A: It was no harder than recruiting for any trial. The eligibility for ATLAS was women who had taken five years of tamoxifen and who were not sure if they should carry on or not. If you can’t decide, then taking part in a study and having the study make the decision for you can be an attractive option, especially if you are worried that you will make the wrong decision. We didn’t know if carrying on was better than stopping, so we had half continue on and half stop. It is thanks to all these women who took part in ATLAS that we now know that carrying on is best.

Q: What are the implications of your findings for how long a woman should stay on an aromatase inhibitor (AI)?

A: We will need to look at findings from the AI trials now underway to determine if 10 years of an AI is better than five.

Q: Who will benefit most from your findings?

A: About 20 percent of breast cancer is in premenopausal women for whom AIs are not an option. Also some women don’t tolerate the AIs, due to the side effects. So, a lot of women switch to tamoxifen. And there are many countries that prefer to use tamoxifen because it is less expensive. For all of these women we now have evidence that 10 years is better than five.

February 27, 2013 at 10:50 pm Leave a comment

ATLAS: In Practice

Judy

Dr. Judy Garber

Dr. Judy Garber is a medical oncologist specializing in breast cancer care at the Dana-Farber Cancer Institute in Boston. BCT spoke with Dr. Garber about how the ATLAS findings will affect breast cancer patients.

Q: Why were people surprised at the finding?

A: I was surprised so many people were surprised. The reason I say that is we have data from the MA-17 study, which looked at women who had had five years    of tamoxifen and then went on an AI or a placebo for five more years. That study was stopped early because the additional two years of medication (aromatase inhibitor) showed a profound effect on recurrence, so we started putting women on five years of an AI after five years of tamoxifen.

Our concern was for women who were premenopausal, whose only option was tamoxifen. We didn’t have any data saying that it was safe or effective for them to stay on tamoxifen longer. Now, we do.

The challenge is trying to figure out for whom this applies. The study included women who were at low and high risk of recurrence and it’s unlikely that additional tamoxifen will benefit everyone equally.  The hope would be that it really benefits those who are highest risk that their breast cancer will return. For women who are at low risk of recurrence, we try to make certain that the side effects will not outweigh the benefits over time.

Q: What about women who stopped taking tamoxifen years ago?

A: I think any woman who has concerns after years off tamoxifen should talk to her doctor about all of this. The study was about continuous tamoxifen use.  If the cancer was long ago and a woman hasn’t had a recurrence, it may not be necessary to consider more tamoxifen, but that should be an individual decision.

Q: How will these findings change breast cancer care?

A: The practice in the U.S. has been five years of tamoxifen—or less in postmenopausal women who might do two-to-three years on tamoxifen and then switch to an AI – based on older data from the NSABP.

It didn’t make sense that ten years of hormonal therapy was better in women after menopause, but only five years was better in premenopausal women.  Therefore, this study will encourage longer duration of tamoxifen therapy in premenopausal women at higher risk of recurrence.  I think this study should also reassure women who took tamoxifen in the past that it is a good and active drug. The challenge will be to identify those women who need 10 years of tamoxifen and those who will get all the benefit they need with 5 years.

If you have any questions about your treatment, you should talk to your doctor. There also are things a woman can do like exercising, minimizing alcohol intake and losing weight that can help reduce risk if she has a hormone receptor positive tumor. Not everyone needs 10 years of tamoxifen. But for those who do need it it’s helpful to know that it can be given safely and that there is additional benefit.

February 27, 2013 at 9:26 pm 6 comments

Calendar/Events

Annie Appleseed Project Evidence-Based Complementary and Alternative Cancer Therapies Conference
Feb 28- March 2
West Palm Beach, FL
Online options: View in Real-Time or ON Demand, up to 30 days after the conference

American Association for Cancer Research Annual Meeting
April 6-7
Washington DC

Living Beyond Breast Cancer Annual Conference for Women Living with Metastatic Breast Cancer
April 13- 14
Philadelphia, PA
Travel grants are available

American Society of Clinical Oncology Annual Meeting
May 31- June 4
Chicago, IL
Patient scholarships are available: contact ASCO at patientadvocate@asco.org or 573-483-1369.

Free Teleconferences and Webinars

“Long-Term Survivorship: Maintaining a Healthy Body Weight”
Register at Living Beyond Breast Cancer
Wednesday, March 6
Noon – 1:00 pm ET

“The Oversimplification of Early Detection: Screening Mammography and Breast Cancer Overdiagnosis”
Register at Breast Cancer Action for Tuesday, March 12,
1pm (PST)/4pm (ET) or Thursday, March 14, 9am (PST) /12pm (ET)

“Understanding the Affordable Care Act in 2013 for People Living with Cancer”
Register at CancerCare.org
Wednesday, March 20
12:30pm – 2:30pm ET

February 23, 2013 at 1:44 am Leave a comment



%d bloggers like this: