Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer

Abstract

Background: Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.

Methods: We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.

Results: Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with goserelin compared with those who were not treated with goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with goserelin compared with those not treated with goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.

Conclusions: Two years of goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when goserelin was added.

Figure 1

Distribution of patients in the Zoladex in Premenopausal Patients (ZIPP) trial (CONSORT flow diagram).

Figure 2

Survival and disease outcomes according to goserelin treatment. A) The percentages (95% confidence interval [CI]) of women treated with goserelin who experienced death, had recurrence, or had a new tumor at 5, 10, and 15 years were 25 (23 to 27), 38 (35 to 41), and 47 (43 to 51), respectively; corresponding percentages in control women were 32 (29 to 35), 43 (40 to 46), and 52 (48 to 55). B) The percentages (95% CI) of women treated with goserelin who died at 5, 10, and 15 years were 12 (10 to 14), 21 (19 to 23), and 29 (26 to 32), respectively; the corresponding percentages in control women were 15 (13 to 17), 26 (23 to 28), and 33 (30 to 36). C) The percentages (95% CI) of women treated with goserelin who had a recurrence at 5, 10, and 15 years were 22 (20 to 24), 31 (28 to 34), and 36 (33 to 39), respectively; the corresponding percentages in control women were 27 (24 to 29), 37 (34 to 40), and 42 (39 to 45). D) The percentages (95% CI) of women treated with goserelin who died from breast cancer at 5, 10, and 15 years were 11 (9 to 13), 20 (18 to 22), and 26 (23 to 29), respectively; the corresponding percentages in control women were 14 (12 to 16), 24 (22 to 26), and 30 (27 to 33). Two-sided P values from log-rank tests are shown.

Figure 3

Survival and disease outcomes according to each of the four treatment groups. Outcomes considered were death, recurrence, or new tumor (A); death from any cause (B); breast cancer recurrence (C); and death due to breast cancer (D). Two-sided P values from log-rank tests.