The publication of NSABP P-1 brought the issue of chemoprevention in high-risk women to the forefront of attention in both the press and the medical literature. While tamoxifen was found clearly to reduce the incidence of breast cancer in high-risk women by about 50%, NSABP P-2 (the STAR trial) is now evaluating the SERM, raloxifene, in this setting. The recent presentation of the initial ATAC trial results — demonstrating an advantage to anastrozole over tamoxifen in contralateral cancers — hints towards future trials of the aromatase inhibitors in the chemoprevention setting. Ultimately, with multiple effective agents, issues of toxicity and side effects will be paramount.

IMPLICATIONS OF ATAC CONTRALATERAL DATA FOR PREVENTION

The odds ratio for the reduction of contralateral breast cancer favoring anastrozole over tamoxifen is 0.42, and the difference emerges within one year. So, there is a staggering 58% reduction over tamoxifen. Tamoxifen can produce a 50% reduction long term. If these findings hold up, we can add another 60% reduction on top of the 50%, and this starts translating into potentially very significant chemoprevention of breast cancer.

—Michael Baum, ChM, FRCS

The ATAC results are very important for the IBIS 2 prevention trial. The ATAC data, particularly on the safety profile, was necessary before the final approval. Now that the data is available, I’m confident that we will be able to proceed rather rapidly with the trial, comparing anastrozole to tamoxifen to placebo in high-risk women and those with DCIS.

—Jack Cuzick, PhD

From the ATAC data we’ve seen, we would expect that anastrozole will dramatically decrease the number of breast cancers and should be superior to tamoxifen in the prevention setting. In addition, in terms of toxicity — although the DVT, pulmonary embolus and stroke risk associated with tamoxifen were just seen in postmenopausal women, anastrozole doesn’t result in these conditions, which can cause death.

—J Michael Dixon, MD, FRCS

The main safety concerns with tamoxifen are the agonist effects (i.e., risk of thromboembolic complications and small risk of endometrial cancer). There’s no question that the safety profile of anastrozole is much better than tamoxifen. Anastrozole is an agent with almost nonexistent side effects — at least in the preliminary analysis of the data — making it a very attractive agent to be evaluated in the prevention setting.

—Aman Buzdar, MD

NSABP P-2: THE STAR TRIAL

There is a great deal of enthusiasm for this 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. I believe that there will be 22,000 more women out there who will enter P-2.

—Norman Wolmark, MD

NSABP P-2: STUDY OF TAMOXIFEN AND RALOXIFENE (STAR) FOR THE PREVENTION OF BREAST CANCER OPEN PROTOCOL PROJECTED ACCRUAL: Approximately 22,000 patients will be accrued to this trial. Quality of life assessed at baseline and six-month intervals to five years then annually thereafter.   PROPOSED IBIS 2 TRIAL: INTERNATIONAL BREAST INTERVENTION STUDY 2     NEW CONTRALATERAL PRIMARY BREAST CANCERS (INVASIVE AND DCIS) IN THE ANASTROZOLE AND TAMOXIFEN ARMS OF THE ATAC TRIAL Anastrozole (n=3125) Tamoxifen (n=3116) Odds Ratio P-value New contralateral primaries 14 33 0.42 0.0068 Baum M. Presentation, 2001 San Antonio Breast Cancer Symposium   What do you believe the results would be of a randomized clinical trial comparing tamoxifen to anastrozole in high-risk postmenopausal women? S U R G E O N S Regarding toxicity   Less toxicity with anastrozole 75% Less toxicity with tamoxifen 5% No significant difference 15% Undetermined 5% Regarding efficacy   Greater benefits with anastrozole 65% No significant difference 25% Undetermined 10% What type of research data would you require to use anastrozole or another aromatase inhibitor in a postmenopausal high-risk woman? S U R G E O N S Would use it based on ATAC data 60% Would only use it if ATAC trial continued to show similar results with longer follow-up 20% Would only use it if a primary prevention trial showed safety and efficacy in high-risk women 10% Undetermined 10% Approximately how many high-risk women (with no personal history of breast cancer) have you treated with tamoxifen in the past year? Mean 2

Day R et al. Health-related quality of life and tamoxifen in breast cancer prevention: A report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Clin Oncol 1999;17(9):2659-69. Abstract

Fisher B et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90(18):1371-88. Abstract

Goss PE, Strasser K. Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 2001;19(3):881-94. Abstract

Jordan VC et al. Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. J Natl Cancer Inst 2001;93(19):1449-1457. Abstract

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

Wickerham DL, Tan-Chiu E. Breast cancer chemoprevention: Current status and future directions. Semin Oncol 2001;28:253-9. Abstract

Home | Meeting Workbook | Educational Supplement | Posters | Opinion Survey |