Affiliations of authors: V. Vogel, National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene Trial; J. P. Costantino, D. L. Wickerham, W. M. Cronin, National Surgical Adjuvant Breast and Bowel Project.
Correspondence to: Victor G. Vogel, M.D., M.H.S., F.A.C.P., University of Pittsburgh Cancer Institute/Magee-Women's Hospital, 300 Halket St., Rm. 3524, Pittsburgh, PA 15213 (e-mail: vvogel{at}mail.magee.edu).
Tamoxifen reduces the development of invasive breast cancer in women at high risk for the disease (1). The Breast Cancer Prevention Trial (BCPT) demonstrated a 49% reduction of invasive breast cancer incidence in all high-risk women randomly assigned to receive tamoxifen and an even larger 86% reduction in invasive breast cancer incidence in women with cellular atypia of either the lobular or ductal type. Similarly, the International Breast Intervention Study I (IBIS I) trial showed a 33% reduction in the risk of developing invasive breast cancer among women randomly assigned to receive tamoxifen when compared with women taking placebo, regardless of their history of cellular atypia (2).
Despite its documented benefits, few high-risk women opt to take tamoxifen for risk reduction. Only 4.7% of women in one study (3) elected to take tamoxifen to reduce risk for developing breast cancer (4). The Gail model is currently the most widely used tool for assessing a woman's risk for breast cancer. In our experience, however, most high-risk women identified with this tool do not pursue risk reduction therapy with tamoxifen.
Analysis of enrollment data from the BCPT and the Study of Tamoxifen and Raloxifene (STAR) trial (5) has uncovered a clinically relevant finding. High-risk patients with atypical lobular or ductal hyperplasia who were counseled about the risks conferred by cellular atypia enrolled in both trials at higher rates than patients who did not have cellular atypia. In the STAR trial with more than 14 000 subjects enrolled, 21% of all risk-eligible women agreed to randomization. In contrast, 36% of risk-eligible women with atypia have enrolled in the study, a 71% relative increase in the proportion randomized. Similarly, BCPT showed a 39% increase in enrollment when comparing risk-eligible women without atypia (23% entry rate) to those with atypia (32% entry rate).
High-risk women may consider the finding of cellular atypia to be a more reliable measure of risk than many of the other factors that contribute to an elevated Gail model score. The data from both the BCPT and STAR suggest that atypia influences a woman's decision to enter a randomized trial to study breast cancer risk reduction. The reason for this finding may be that the presence of atypia influences a woman's perception of the magnitude of her risk for breast cancer and also enhances her recognition of an improved benefit-to-risk ratio for taking tamoxifen. This observation should be evaluated further in studies investigating the ability of other pharmacologic agents to reduce the risk of breast cancer.
Prospective observations will need to confirm that the presence of cellular atypia in ductal lavage specimens (6) has the same implications for the subsequent risk of developing invasive breast cancer conferred by atypia seen on histological biopsy (7), nipple aspirate fluid, or in fine-needle aspiration specimens. There is no reason a priori, however, to believe that atypia identified via ductal lavage will have a different implication than atypia found by other means. Atypia identified by ductal lavage will be assigned the same clinical significance as atypia identified by histologic tissue sections when Gail model risk is calculated for determining eligibility for the STAR trial.
REFERENCES
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2 Cuzick J. IBIS-I and ATAC trials. Update and implications for IBIS-II. Eur J Cancer 2002;38(Suppl 1):S17. Additional information is available at http://www.medscape.com/viewarticle/431664?anonvar=m2e5d7a8n9o5n2x3e4xrt567.
3 Port ER, Montgomery LL, Heerdt AS, Borgen PL. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol 2001;8:5805.
4 Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989;81:187986.[Abstract]
5 Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Wolmark N. The study of tamoxifen and raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial. Clin Breast Cancer 2002;3:1539.[Medline]
6 Dooley WC, Ljung BM, Veronesi U, Cazzaniga M, Elledge RM, O'Shaughnessy JA, et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst 2001;93:162432.
7 Dupont WD, Parl FF, Hartman WH, Brinton LA, Winfield AC, Worrell JA, et al. Breast cancer risk associated with proliferative disease and atypical hyperplasia. Cancer 1993;71:125865.[Medline]
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