SAN ANTONIOYounger, premenopausal estrogen-receptor
(ER)-positive breast cancer patients should be aware that there is an
alternative to adjuvant chemotherapy, Michael Baum, MD,
professor of surgery, University College, London, said at the San
Dr. Baum presented data from the ZIPP (Zoladex in Premenopausal
Patients) trial, on behalf of four European study groups: the Cancer
Research Campaign (CRC) Breast Cancer Trials Group; the Stockholm
Breast Cancer Study Group, the South East Sweden Breast Cancer Group,
and Gruppo Interdisciplinare Valutazione Interventi Oncologia
From the world overview, Dr.Baum told ONI in an
interview, we learned that chemotherapy and ovarian ablation
are effective in premenopausal women, while tamoxifen (Nolvadex) is
effective in postmenopausal women. That opened up many questions
about the man-agement of breast cancer in premenopausal women.
The questions included: Could temporary ovarian suppression, using
the LHRH analog goserelin (Zoladex), successfully fight breast cancer
in premenopausal patients? Does chemotherapy work by ovarian
suppression? Does tamoxifen have an effect in premenopausal women?
It was difficult to address all these questions at the same
time, Dr. Baum told ONI, which is why the four study groups
designed a 2 × 2 factorial trial. After surgery, premenopausal
patients with early-stage breast cancer were randomized to one of
four arms: 3.6 mg of goserelin every 4 weeks for 2 years; tamoxifen
(20 or 40 mg) daily for 2 years; combination goserelin and tamoxifen;
and no adjunctive hormonal therapy.
Adjuvant Chemo Allowed
Eventually, Dr. Baum said, it was decided it would be difficult
to withhold chemotherapy from node-positive patients, so
participating physicians could elect to provide adjunctive
chemotherapy. Indeed, of the original 2,648 patients (a larger
number than in the overview of ovarian ablation), 44% were node
positive and, of these, the majority received adjuvant chemotherapy.
Dr. Baum noted that, initially, the main objective was to examine the
difference in response between goserelin with tamoxifen and goserelin
without tamoxifen and between tamoxifen with goserelin and tamoxifen
But again we were overtaken by events, he said.
Halfway through the trial there was unequivocal evidence of the
benefits of tamoxifen in premenopausal women. Thus, many of the
centers elected to give tamoxifen and randomized only to goserelin or
The patients had a median age of 44, with about 24% younger than 40.
About 40% in each group were node positive, and about 60% in each
group were ER positive.
Dr. Baum presented results on the effects of goserelin vs no
goserelin with a median follow-up of 5 years. The number of first
events was 411 in the no-goserelin group vs 330 in the goserelin
Goserelin had a significant effect on disease-free survival,
with a relative risk of .77, a 23% risk reduction, compared with no
goserelin, he said. There was a trend toward improved overall
survival, but this has not yet reached significance, he added.
The major reduction was in local recurrences (163 vs 117). But Dr.
Baum also cited an interesting finding regarding
contralateral breast cancer: 42 cases in the control group vs 28 in
the goserelin group.
This is approaching significance, he noted, and is
fairly compelling evidence that we should be concentrating trials of
Zoladex in the primary prevention of breast cancer in high-risk
Not surprisingly, he said, goserelin showed a greater effect in
ER-positive patients than in ER-negative patients. The ER-positive
patients had a relative risk of .71 for disease-free survival,
compared with the overall effect of .77. There appears to be no
benefit emerging for the ER-negative cases, Dr. Baum commented.
In the presence of chemotherapy, he told ONI, there was very
little additional benefit to using goserelin. Thats no surprise
if chemotherapy mediates the drugs effects by causing ovarian
suppression, which is what we suspect. This so-called Zoladex
effect seems to be more effective in women age 40 or less than in
those over age 40.
Dr. Baum concluded that goserelin was most beneficial in the younger
group of ER-positive patients who were not concurrently receiving
chemotherapy. With proper investigation, he told ONI, in a year
or two, we may have an alternative to chemotherapy that will preserve
a womans fertility.