) Hodgkin's Disease carries an excellent prognosis, with the majority of patients cured of their primary tumor. However, late complications of therapy in these patients are of increasing concern, especially new primary cancers of particular importance in this group is the increased risk of breast cancer among female Hodgkin's disease survivors who received mantle or chest radiation (RR approximate 20 by 15 yrs after treatment). Tamoxifen has been shown to reduce the risk of breast cancer by nearly 50percents in women at increased risk on the basis factors considered in the Gail model, DCIS or prior breast cancer II. It has not yet been evaluated in radiogenic breast cancer. HD survivors may also experience early menopause if their HD treatment included chemotherapy 12, and early atherosclerotic heart disease l3,14 and other second cancer risk from radiation or combined modalities I. These concerns may affect the risk/benefit considerations of tamoxifen in this high risk population whose risk becomes manifest at young ages. Because of these issues, it seems important to prove, rather than assume, that tamoxifen ireduces breast cancer risk in this population. However, since there are a limited number of women available for a study of sufficient size to address the question with sufficient power, demonstration of feasibility seems critical. In the proposed study, we will address aspects of feasibility , including recruitment/acceptance, adherence, toxicities and quality of life, and reproductive hormone status. We propose to recruit 50 female Hodgkin's Disease survivors whose treatment included radiation therapy (mantle or other chest), diagnosed before age 30, current age greater than 30 years, greater than 8 years from radiation to participate in a pilot study in which they will receive tamoxifen for 2 years on study, and 5 years in total. We will estimate recruitment rates, evaluate adherence, and assess quality of life and toxicities using measures employed in the BCPT, as well as questions developed for this population. Our advisory board will consider the one year data and assist us in deciding whether or not to proceed to attempt the larger study. A definitive randomized trial would be feasible with available HD survivors if adherence were 90 percents, based upon an estimated absolute risk of 8 percents over a 5 year period in women without tamoxifen. This is a risk much greater than the average risk in the BCPT cohort, permitting the smaller sample size. We will also evaluate mammographic density as a potential intermediate endpoint that might permit more rapid completion of a randomized study.
