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.
Protocol Variations Allowed to Encourage Enrollment
The protocol for the large-scale European study of goserelin
The studys pragmatic design is apparent in the fact
Some centers included only ER-positive patients; others did not
The method of randomization was also at the discretion of the
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.