Danazol treatment of severely symptomatic fibrocystic breast disease and long‐term follow‐up—the Hjørring project
Authors: Tobiassen Tobias , Rasmussen Thorkild , Döberl Anton , Rannevik Gunnar 
Published: December 2009

Abstract. The purpose of the investigation was to study various aspects of danazol treatment in patients with fibro‐cystic breast disease and pronounced mastodynia. To qualify for inclusion, the patients in this study had to have a mammographically confirmed prominent glandular structure and/or severe cystic breast disease, associated with pronounced cyclical mastodynia lasting at least one week per menstrual bycle for more than 6 months. They also had to be premenopausal and not undergoing hormonal therapy.

Of 109 patients with a mean age of 40±6.2 (SD) years, who completed 6 months' treatment with danazol, 65% had a pre‐treatment history of more than 5 years. According to detailed mammographic characterization, only 18% of the patients had no visible cysts. Of the 82% with visible cysts, half presented with both small (< 1 cm) and large cysts. The patients were treated in two consecutive groups, 55 patients receiving 400 mg a day and 54 patients 200 mg a day.

The therapeutic response was similar following both dosages. Mastodynia responded rapidly and total elimination was noted in about 90% of cases. A marked decrease in prominence of palpable structure was observed in virtually all patients. Mammographically, a decrease in the amount of glandular tissue was observed. These changes during treatment were statistically highly significant (p<0.001), irrespective of dose or category of patient. Non‐cystic nodularities gradually decreased in 85% and resolved completely in 58% of the cases, but the degree of resolution in the groups of patients with no or only small (< 1 cm) visible cysts was significantly greater (p < 0.02 or less) than in the group which also had large cysts and which included the most severe and intractable cases.

The mammographical visualization of cysts, ductal system, and fibrous tissue increased initially due to the marked regression of obscuring glandular tissue. Thereafter, a decrease in the number and spread of small cysts was observed in a significant proportion of patients and in some cases a reduction in duct diameter could be demonstrated by means of galactography. Nipple discharge also decreased. The extent of fibrosis appeared to be unaffected by therapy. In the 46 patients with large cysts and, in most cases, a documented history of repeated cyst formation, danazol treatment was found to arrest the development of new cysts and to, Fibrocystic breast disease, mammographic evaluation of treatment, cyst formation, post‐treatment relapse, danazol treatment was found to arrest the development of new cysts and to prevent recurrence for a considerable time thereafter. Within 2½ years of treatment, only 9 patients had recurrence of large cysts and even in these cases the rate of cyst formation was less than half of the pre‐treatment rate.

Menstrual irregularities or amenorrhea were noted in 66 and 85010 during danazol treatment with 200 and 400 mg, respectively. A moderate weight gain of approximately 2 kg was the most common side effect. Other side effects were not infrequent, but usually well tolerated, particularly at the 200 mg daily dose. In no case was there any need to stop treatment on medical grounds and laboratory safety monitoring did not reveal consistent changes.

During a post‐treatment observation period of up to 3 years, the patients were followed with regard to symptomatic relapse, defined as recurrent mastodynia of similar intensity as before treatment in still premenopausal women. In patients treated with 200 mg, the cumulative relapse rate was 67% during a mean observation period of 18.2 months, with a mean interval to relapse of 9.2 months. In patients treated with 400 mg, the cumulative relapse rate was 52% within a mean period of 27. I months and a mean interval to relapse of 12.2 months.

Clinical and, in particular, mammographic findings point to an involution and apparent inactivation of glandular tissue as the key to the therapeutic action of danazol in the treatment of fibrocystic breast disease, affecting not only subjective symptoms, but also causing profound changes in mammographic structure and activity, as evidenced by arrested cyst formation.