CORRESPONDENCE

Re: Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study

Richard R. Love

Correspondence to: Richard R. Love, M.D., Department of Medicine, University of Wisconsin Medical School, 1300 University Ave., 7C, Madison, WI 53706 (e-mail: rrlove{at}facstaff.wisc.edu).

Despite admonitions that physicians should discuss current information on tamoxifen with their patients, the preponderance of scientific primary and secondary reports and commentaries focus on relative risk information. While current trial results do not answer several important questions and while our individual risk assessment tools are less than ideal, we can lay out absolute risk and benefit data.

Phillips et al. (1) have helped us all by portraying the impact of breast cancer in a Canadian population. Their life table numbers emphasize that, in a general western population of 1000, the numbers of deaths from breast cancer are small. For example, among women aged 50-54 years and women aged 60-64 years, three deaths might occur in each age group. These numbers emphasize the importance of focusing on women at substantially greater than average risk for this disease.

While there is reluctance to lay out absolute numbers of excess or prevented events associated with tamoxifen therapy [p. 1383 in (2)], healthy women considering this issue request such information. Using the actual average annual rates in the P-1 study report (2) and multiplying these rates by 5 (excepting the vasomotor and gynecologic symptom numbers), the numbers in Table 1Go result. It is notable that some event numbers may in fact represent chance occurrences. The excess levels of vasomotor and gynecologic symptoms with tamoxifen are consistent with other data; e.g., in a carefully studied population of postmenopausal women, we found that, after 6 months and 12 months, respectively, an excess of 23% and 27% of tamoxifen recipients reported substantial overall toxicity (3). Such numbers would suggest dropout rates higher than those that actually occurred in the P-1 study.


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Table 1. Excess or prevented events if cohorts of 1000 high-risk healthy women aged less than 50 years or aged 50 years or more with uteri are treated with tamoxifen for 5 years*

 
What this portrayal of absolute events shows is that, in high-risk cohorts under and 50 years of age or more, the numbers of prevented breast cancers over a 5-year period are small; the number of prevented events in women under 50 years of age markedly exceeds the number of unfavorable events (ignoring symptoms); the number of prevented events in women aged 50 years or more is marginally fewer than the number of unfavorable events (without or with the excess uterine cancer numbers); and 15%-25% (depending on how one looks at the data on symptoms) of all treated women will have what they view as substantial toxicity. With breast cancer prevention, preclinical hormone receptor-positive lesions are treated; the prognosis is excellent for women with clinically diagnosed, small hormone receptor-positive cancers (4). While, in the P-1 study, no endometrial cancer deaths occurred, in the meta-analysis of adjuvant therapy with tamoxifen (4), an excess of endometrial cancer mortality was found.

Until further follow-up data from the P-1 study or from other studies become available, these absolute numbers tell us roughly what we know.

NOTES

Editor's note: Zeneca Pharmaceuticals, the manufacturer of tamoxifen, is supplying the drug at cost for a clinical trial in which Dr. Love is the principal investigator.

REFERENCES

1 Phillips KA, Glendon G, Knight JA. Putting the risk of breast cancer in perspective. N Engl J Med 1999;340:141-4.[Free Full Text]

2 Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, 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;90:1371-88.[Abstract/Free Full Text]

3 Love RR, Cameron L, Connell BL, Leventhal H. Symptoms associated with tamoxifen treatment in postmenopausal women. Arch Intern Med 1991;151:1842-7.[Abstract]

4 Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;351:1451-67.[Medline]


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