Ovarian suppression with luteinising hormone-releasing hormone (LHRH) agonists have shown to reduce the risk of recurrence and mortality in pre-menopausal women with hormone receptor positive early breast cancer.r The results of the SOFT and TEXT trials showed that recurrence is significantly reduced in patients treated with exemestane plus an LHRH agonist compared with those treated with tamoxifen plus an LHRH.r
Although the duration of LHRH treatment was 2 years in most trials, the optimum duration of treatment with LHRH agonists is unknown with some trials using LHRH for 18 months, 3 years, or 5 years.r Patients in the SOFT and TEXT trials received LHRH treatment for a total of 5 years.r
Data on the long-term benefit of LHRH agonists is provided by the ZIPP trial, a randomised controlled trial involving 2706 patients comparing goserelin alone, tamoxifen alone, goserelin and tamoxifen or no treatment following primary therapy (surgery with or without radiation therapy/chemotherapy) in premenopausal women with invasive, operable breast cancer.r Between August 1987 and March 1999, 469 women received goserelin alone (3.6 mg every 4 weeks), 879 women received tamoxifen alone (20 or 40 mg daily), 882 women received both treatments and 476 women did not receive endocrine therapy. Treatment was administered for 2 years. The primary end point was event-free survival (EFS) and secondary end points were overall survival (OS), risk of recurrence and risk of dying from breast cancer.r
Efficacy
After a median follow up of 12 years, goserelin was associated with a risk reduction in all four endpoints: the risk of having as EFS event (HR=0.82, 95% CI 0.73 to 0.92, p =0.001), overall mortality (HR=0.83, 95% CI 0.71 to 0.96, p =0.013), the risk of recurrence (HR=0.81, 95% CI 0.71 to 0.92, p =0.001) and breast cancer mortality (HR=0.82, 95% CI 0.70 to 0.96, p =0.03).r
Women who received tamoxifen had a smaller benefit for survival and recurrence due to goserelin.
© J Natl Cancer Inst 2009
© J Natl Cancer Inst 2009
Toxicity
Amenorrhoea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhoea was generally permanent in CMF patients (22.6% v 76.9% amenorrhoeic at 3 years) Oestrogen related side effects were higher with goserelin but reduced to a level below that of CMF when treatment stopped.r
© Journal of Clinical Oncology 2002