Reversal of gonadotropin-releasing hormone agonist induced reductions in mammographic densities on stopping treatment

Previously, we described the reduction in mammographic densities that occur red in premenopausal women after 12 months on a hormonal regimen designed t o be chemopreventive for breast (and ovarian) cancer consisting of a gonado tropin-releasing hormone agonist (GnRHA) plus low-dose add-back estrogen-pr ogestin. We sought to determine whether the density reduction persisted wit h continuation of the regimen for 24 months, and, if so, whether the densit ies would return to baseline after the regimen was discontinued. Twenty-one women, 27-40 years of age with a 5-fold greater than normal risk of breast cancer, were randomly assigned in a 2:1 ratio to the treatment group (14 w omen) and to a control group (7 women). The percentage of mammographic dens ities, calculated as the proportion of the breast area on the mammogram con taining densities, were assessed blindly using a computer-based threshold m ethod at baseline, after 12 and 24 months of treatment, and at between 6 an d 12 months after treatment was stopped. The previously described percentag e of mammographic density reductions of 9.7% (P = 0.012) after 12 months of treatment were increased slightly to 11.4% (P = 0.010) after 24 months of treatment, but the additional change was not statistically significant. Ten of 11 treated women assessed at 24 months had reduced percentages of mammo graphic densities compared with baseline. Six to 12 months after completion of treatment, the mean percentage of mammographic density in the treated g roup was no different from that at baseline (mean decline of 2.0%; P = 0.73 ). The women in the control group had no statistically significant changes in densities over the period of the study. Reductions in mammographic densi ties engendered by the GnRHA plus a low-dose add-back estrogen-progestin re gimen persist as long as the women receive treatment. The densities return to baseline when the women resume normal menstrual cycles. These results co nfirm that mammographic densities are influenced by ovarian function. Impro ved efficacy of mammographic screening is to be expected as long as a woman continues on such a regimen. Whether such a regimen is chemopreventive for breast cancer remains to be established, but the recent report on a random ized trial of use of GnRHA alone in premenopausal breast cancer cases showi ng a marked reduction in incidence of contralateral disease provides strong support for the hypothesis.