Density lowering effect of ovarian function suppression in premenopausal breast cancer patients who had no density change with one year of tamoxifen treatment (DELFINO study)

Abstract

Background Mammographic density has been known to be a risk factor for breast cancer. Moreover, tamoxifen reduces mammographic density, and the change in mammographic density is a predictive surrogate marker for response to adjuvant tamoxifen therapy. If there is no change or rather an increase in mammographic density, the effect of tamoxifen therapy is considered to be less, and intervention for additional treatment such as ovarian function suppression (OFS) may be considered in the group with a low response to the treatment. However, the benefits of adding OFS in premenopausal hormone receptor-positive breast cancer are unclear. In this trial, we assumed that adding OFS to tamoxifen would have a further reduction of mammographic density compared with tamoxifen alone in premenopausal estrogen receptor-positive breast cancer.

Trial design In this phase III, 3-arm (observation arm + randomized 2-arm), randomized, controlled trial, we planned to assign premenopausal patients who underwent surgery for invasive breast carcinoma. The main inclusion criteria are premenopausal women with stage I-III, estrogen receptor-positive breast cancer who underwent standard treatment including surgery, and are planned tamoxifen treatment. The main exclusion criteria are bilateral breast cancer, prior endocrine therapy, postmenopausal status, and unavailable mammographic density via Volpara before and during tamoxifen treatment. If mammographic density reduction via Volpara (MDR) ≥10% after one year of tamoxifen treatment, the patients Keep tamoxifen treatment. If MDR <10% after one year of tamoxifen treatment, the patients randomized (1:1) to add on ovary function suppression (OFS) to tamoxifen, or to keep tamoxifen alone after one year of tamoxifen treatment. The primary endpoint is MDR after 1yr of randomization. Under the assumption that the MDR after 1yr of randomization would be 6 ± 7% vs. 10 ± 7% in the tamoxifen alone group and adding OFS group, respectively, a total of 224 patients were calculated to have 80% power to show a 4% difference in MDR with a significance level of 0.05.

Clinical trial identification NCT03664895