STOCKHOLM, Sweden-Premenopausal breast cancer patients who received 2 years of treatment with the LHRH analogue goserelin (Zoladex) showed significantly improved event-free survival, reduction of contralateral breast cancers, and a trend toward improved overall survival, Lars Rutqvist, MD, of the Karolinska Hospital in Stockholm, Sweden, reported at the 35th annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.
STOCKHOLM, SwedenPremenopausal breast cancer patients who received 2 years of treatment with the LHRH analogue goserelin (Zoladex) showed significantly improved event-free survival, reduction of contralateral breast cancers, and a trend toward improved overall survival, Lars Rutqvist, MD, of the Karolinska Hospital in Stockholm, Sweden, reported at the 35th annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.
Dr. Rutqvist presented the first report of a large-scale randomized trial underway since the late 1980s by four European study groups (the Cancer Research Campaign Breast Cancer Trials Group, Stockholm Breast Cancer Study Group, South-East Sweden Breast Cancer Group, and Gruppo Interdisciplinare Valutazi-one Interventi in Oncologia).
After primary surgery, 2,631 premenopausal early stage breast cancer patients were randomized to receive one of four regimens:
Goserelin, given as a depot subcutaneous injection (26 monthly injections) for 2 years.
Tamoxifen (Nolvadex) (20 mg or 40 mg) daily for 2 years.
Both goserelin and tamoxifen therapy for 2 years.
No adjuvant hormonal therapy.
Alternatively, patients electively received tamoxifen or not and were randomized just for goserelin/no goserelin (see box). Rutqvist noted that about 45% of the patients included in the study were node positive. Among the 1,577 patients (60%) for whom estrogen-receptor (ER) status was recorded, somewhat more than 70% were classified as ER positive. Adjuvant chemotherapy was used in 43% of the patients.
The protocol for the large-scale European study of goserelin (Zoladex) in premenopausal breast cancer allowed for considerable variation in the patient populations studied, Dr. Lars Rutqvist said in his ASCO presentation. This was done to encourage greater physician participation and patient recruitment.
The studys pragmatic design is apparent in the fact that some centers used actual menstrual status (premenopausal) as entry criteria while others used age under 50 years as the cutoff for inclusion.
Some centers included only ER-positive patients; others did not select on the basis of hormone-receptor status. Some centers allowed chemotherapy in defined subgroups. Inclusion according to type of surgery and use of postoperative radiation also varied according to the individual center.
The method of randomization was also at the discretion of the individual centerwhether patients would be randomized to all four arms of the trial or just to goserelin or no goserelin.
The current analysis focused only on the effect of goserelin, comparing the groups that received goserelin or goserelin plus tamoxifen with the two no-goserelin groups. The benefit of adjuvant tam-oxifen in premenopausal breast cancer is now fairly well established, Dr. Rutqvist explained. The median follow-up was slightly more than 4 years in both groups.
During follow-up, fewer patients taking goserelin developed a first eventlocal recurrence, distant recurrence, or a new primary tumorcompared with the no-goserelin groups (20% vs 24.9%,
P = .001). Consequently, Dr. Rutqvist reported, event-free survival for goserelin vs no goserelin was highly significant favoring the goserelin group, with a relative hazard ratio of 0.77 (a 23% relative reduction). Event-free survival for the controls was 69% vs 75.2% for the goserelin patients, so the benefit in absolute terms was about 6%, he said.
For overall survival, the relative risk among goserelin-treated patients was 0.84, a 16% relative reduction, but this was not statistically significant (P = .12). Overall survival was roughly similar in the two groups during the first 2 years of observation, but after 2 years the curves started to diverge, with a continued divergence during the entire period of observation, Dr. Rutqvist said.
In univariate analyses, goserelins trend toward reducing first events was somewhat smaller among patients receiving adjuvant chemotherapy (0.88 relative risk vs 0.69 for no chemotherapy). The benefit of goserelin appeared to be greater among patients classified as ER positive (relative risk, 0.71 vs 0.94 among ER negatives), but this also was not significant.
Treatment with goserelin appeared to offer substantial protection against new primaries in the contralateral breast, Dr. Rutqvist said. Eighteen patients receiving goserelin developed contralateral breast cancer as the first event vs 36 in the control group (P = .05).
Dr. Rutqvist said that an analysis of side effects associated with the different treatments in the trial is currently underway.