SAN ANTONIOEstrogen suppression using goserelin (Zoladex)
increased the relapse-free interval in premenopausal women with early
stage breast cancer, compared with no goserelin, according to an
interim analysis of the ZIPP (Zoladex in Premenopausal Patients)
trial. Michael Baum, MD, of the Cancer Research Campaign, London,
presented the results at the San Antonio Breast Cancer Symposium.
The origins of this trial go back to the world overview
of 1995, Dr. Baum said. The surprise finding of the
overview was the effectiveness of ovarian ablation. The ZIPP
trial, with 2,648 participants, is larger than the overview of
ovarian ablation, with 2,000, he noted.
Patients were randomized after surgery to one of four groups: no
adjuvant hormonal therapy, goserelin for 2 years, tamoxifen
(Nolvadex) for 2 years, and both goserelin and tamoxifen for 2 years.
As part of the primary treatment, physicians could elect to use
chemotherapy in high-risk women, Dr. Baum said, and, in fact, most
node-positive women received chemotherapy.
Furthermore, midway through the recruitment phase of the trial,
physicians were given the option to offer patients tamoxifen and only
randomize patients to goserelin or no goserelin.
With a median duration of follow-up of just over 5 years, there have
been 411 first events (local recurrence, distant recurrence, or new
primary tumor) in patients not receiving goserelin and 330 among
those receiving goserelin, resulting in a relative risk for
event-free survival of .77, highly significant favoring
goserelin, Dr. Baum said.
The major reduction in events has been in local recurrence, but Dr.
Baum noted a trend toward a reduction in new primary tumors in the
contralateral breast: 42 cases have been seen in those not receiving
goserelin vs 28 in those receiving goserelin. Dr. Baum called this
fairly compelling evidence that we should be concentrating
trials of goserelin in the primary prevention of breast cancer in
high-risk young women.
Subgroup analyses showed that in patients who did not receive
adjuvant chemotherapy, the effects of goserelin on disease-free
survival were greater, with a relative risk of .69, compared with the
overall effect of .77. In the presence of chemotherapy, we
appear to lose that effect, he said.
As might be expected, the effect of goserelin is predominantly seen
in ER-positive patients, with a relative risk of .71. No
benefit is emerging for the ER-negative cases, Dr. Baum said.
There is also a significant trend toward greater benefit of goserelin
among younger women. This becomes most dramatic when we split
the data above and below the age of 40, he said.
Dr. Baum concluded, At a median follow-up of 5 years,
premenopausal patients receiving goserelin have a significantly
prolonged event-free survival. There is an improved overall survival,
but this is not as yet significant. Furthermore, pending formal
multivariate analyses, I think it is reasonable to suggest that, for
disease-free survival, goserelin was most beneficial in the young,
ER-positive patients who were not concurrently receiving chemotherapy.
Responding to a question from the audience, Dr. Baum agreed that
goserelin may not produce better results than adjuvant chemotherapy
in younger women, but stressed that goserelin is a reversible form of
ovarian suppression and does potentially offer a choice for the
very young premenopausal woman who wishes to retain her