Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer.
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.
Hackshaw
Allan
A
Cancer Research UK & UCL Cancer Trials Centre, University College London, 90 Tottenham Court Rd, London W1T 4TJ, UK. ah@ctc.ucl.ac.uk
Baum
Michael
M
Fornander
Tommy
T
Nordenskjold
Bo
B
Nicolucci
Antonio
A
Monson
Kathryn
K
Forsyth
Sharon
S
Reczko
Krystyna
K
Johansson
Ulla
U
Fohlin
Helena
H
Valentini
Miriam
M
Sainsbury
Richard
R
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004347:Drug Interactions; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause; D018570:Risk Assessment; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone