Carcinoma In Situ Outcomes in National Surgical Adjuvant Breast and Bowel Project Breast Cancer Chemoprevention Trials

Selective estrogen receptor modulators (SERMs) are established in the treatment of estrogen receptor (ER)-positive breast cancer, and four decades of basic and preclinical research have shown them to be ideal agents for the reduction of the risk of breast cancer in high- risk pre- and postmenopausal women. The National Surgical Adjuvant Breast and Bowel Project (NSABP) has conducted many clinical trials that used SERMs for the treatment and prevention of breast cancer. The trials were designed to assess a number of clini- cal and pathological outcomes including both invasive and in situ breast carcinomas. Here, we summarize the previously published data from two of those trials and also highlight the most recent data related to in situ events in the Study of Tamoxifen and Raloxifene (STAR) NSABP breast cancer risk reduction trial using tamoxifen. Background In the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (BCPT), the reduction in risk of noninvasive breast cancer was 50%. There were 93 cases in women receiving placebo and 60 in those receiving tamoxifen (P = .008). Through 7 years of follow-up, the cumulative incidence of noninva- sive breast cancer among the placebo group was 15.8 per 1000 women vs 10.2 per 1000 women in the tamoxi- fen group. In the initial report of the Study of Tamoxifen and Raloxifene (STAR trial), the rate for noninvasive breast cancer was 1.51 per 1000 women assigned to tamoxifen and 2.11 per 1000 women assigned to raloxifene (risk ratio, 1.40; 95% confidence interval = 0.98 to 2.00). Methods Additional follow-up of the NSABP STAR trial through March 31, 2009 is reported with a focus on noninvasive breast cancer events. Results Through 81 months of median follow-up in the NSABP STAR trial, there are 137 cases of noninvasive breast cancer in the raloxifene group compared with 111 cases in the tamoxifen group (risk ratio = 1.02, 95% confi- dence interval = 0.61 to 1.70). The occurrence of ductal carcinoma in situ with raloxifene was seen more fre- quently among women with lower baseline Gail scores and no atypical hyperplasia than in women taking tamoxifen therapy. Raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive breast cancer. Conclusions Although these data indicate that raloxifene offers less protection than tamoxifen for postmenopausal women who are at increased risk for both invasive and noninvasive breast cancer, the favorable risk-benefit profile for raloxifene affords acceptable clinical reduction in the risk of in situ cancers among postmenopausal women.