Current breast cancer clinical trials

The International Breast Cancer Overview has clearly demonstrated that adjuvant ovarian ablation significantly reduces mortality in premenopausal patients and that tamoxifen reduces mortality in both pre- and postmenopausal women with ER-positive tumors. Current clinical trials are addressing a number of important issues related to these two key interventions, including the impact of combining these therapies with or without chemotherapy. While five years is the accepted current standard duration of adjuvant tamoxifen, randomized trials are evaluating more prolonged treatment or sequencing tamoxifen with aromatase inhibitors. Other SERMS are also being evaluated in various clinical settings including the STAR trial, which compares raloxifene to tamoxifen in high-risk women.

 

 

SELECT PUBLICATIONS

Baum M et al. Management of premenopausal women with early breast cancer: Is there a role for goserelin? Proc ASCO 2001;Abstract 103.

Davidson, N et al. Effect of chemohormonal therapy in premenopausal, node (+), receptor (+) breast cancer: An Eastern Cooperative Oncology Group phase III Intergroup trial (E5188, INT-0101). Proc ASCO 1999;Abstract 249A, 67A.

Fisher B et al. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: Updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst 2001;93(9):684-90. Abstract

Jakesz R. Comparison of adjuvant therapy with tamoxifen and goserelin vs CMF in premenopausal stage I and II hormone-responsive breast cancer patients: Four-year results of Austrian Breast Cancer Study Group (ABCSG) Trial 5. Proc ASCO 1999;Abstract 250.

O'Regan RM, Jordan VC. Tamoxifen to raloxifene and beyond. Semin Oncol 2001;28(3):260-73. Abstract

Rockhill B et al. Validation of the Gail et al model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst 2001;93(5):358-66. Abstract

Stewart HJ et al. Scottish adjuvant tamoxifen trial: A randomized study updated to 15 years. J Natl Cancer Inst 2001;93(6):456-62. Abstract

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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NSABP P-2: THE STAR TRIAL
There is a great deal of enthusiasm for the STAR trial, and an enormous amount of credit has to go to the NSABP members who are committed to moving the state-of-the-art forward. That’s their primary commitment, and it was the primary commitment of the 13,388 selfless and courageous women who entered the P-1 trial. And I believe that there will be 22,000 more women out there who will enter P-2.

— Norman Wolmark, MD

RALOXIFENE
Raloxifene has been studied in a completely different population, namely older postmenopausal women selected for osteoporosis risk, and some data suggest that women with decreased bone density are at decreased breast cancer risk. The raloxifene data on breast cancer risk reduction is promising, but right now for postmenopausal women who are at increased risk, tamoxifen is clearly the drug of choice outside of a clinical trial. Also, raloxifene is only for postmenopausal women; there are no safety data in premenopausal women.

— Monica Morrow, MD

DURATION OF TAMOXIFEN THERAPY
Breast cancer is a disease with at least a 20-year natural history. The question is, “Would 10 years of tamoxifen be better than five years for providing protection against recurrence in the second decade after diagnosis?” There are almost as many breast cancer deaths in the second decade after diagnosis as in the first. We’ve really got to think on a long-term scale. When we do that, the idea that 10 years might be better than five years actually becomes quite interesting. We’ve got virtually no information on that second decade.

—Richard Peto, FRS

INTERGROUP 0101 STUDY OF ADJUVANT OVARIAN ABLATION
The study was designed a long time ago, and at a time when there was increasing interest in ovarian ablation because of the meta-analysis and because there were now drugs available that could lead to chemical castration as opposed to surgical ablation.

In the best of all worlds we would have had a 4th arm of CAF followed by tamoxifen, but at the time we weren't sure that we could accrue to that trial in a timely fashion and have something to talk about.

The disease-free survival was better for the group receiving CAFZT compared to CAFZ. There was a borderline impact of CAFZ compared to CAF. An unplanned preliminary, retrospective subset analysis demonstrated that younger women — arbitrarily defined as women under the age of 40 — seemed to do better with Zoladex®(goserelin acetate implant). Perhaps that's not surprising, because those women are the least likely to be made postmenopausal by chemotherapy. There's also a suggestion that women with premenopausal estrogen levels after chemotherapy were destined to derive benefit from Zoladex. The big clinical question now is what to do with the young woman who is premenopausal at the end of chemotherapy? Most of them receive tamoxifen as a matter of routine, and I personally am not using LHRH agonists in that situation right now, but some of our very good colleagues have looked at these trial results and said that they think it is legitimate to do.

— Nancy E Davidson, MD

ADJUVANT OVARIAN ABLATION
We now have several trials demonstrating that in receptor-positive premenopausal patients, ovarian ablation is as effective as CMF — and, in fact, there’s almost a suggestion that it is better. In the ECOG study (Intergroup 0101), patients received CAF, which everyone would consider state-of-the-art chemotherapy. In that trial, there was additional benefit from adding ovarian ablation to CAF — certainly among women under age 40. That study really changed my thinking, and I have now moved to the point that if a woman receives adjuvant chemotherapy and does not stop menstruating, I routinely add the LHRH agonist, Zoladex, with tamoxifen.

— I Craig Henderson, MD

AUSTRIAN TRIAL: ABCSG 12
The basis for this trial was a study presented at ASCO whereby patients were randomized either to CMF or to Zoladex plus tamoxifen. This was in premenopausal, ER-positive patients, and what it showed was that the early recurrence-free survival curves were in favor of the endocrine arm. And so they have taken that as the control arm for the next study, and they’re now comparing Zoladex plus tamoxifen to Zoladex plus Arimidex.

— John F Robertson, MD, FRCS
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