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Bone Mineral Density In Premenopausal Patients In A Randomized Trial Of Adjuvant Endocrine Therapy (ZIPP-TRIAL)

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 15, 2001

Presenter: Asgerdur Sverrisdóttir
Affiliation: University Hospital, Stockholm, Sweden

Background:

There is evidence that ovarian ablation can improve survival in pre-menopausal patients with early-stage breast cancer. However, there is concern that a premature menopause may be associated with long-term adverse side effects, such as a decreased bone mineral density. Recently, early results from trials using LHRH- analogues have indicated significant benefits in terms of recurrence-free survival and trends towards improved survival with only 2 years of treatment. This study evaluates the risk of osteoporosis in premenopausal women treated with endocrine therapy for early stage breast cancer.

Materials and Methods:

• This study analyzed total body bone mineral content (TBBM) in 73 pre-menopausal patients with node-negative breast cancer who were included in a controlled clinical trial of adjuvant endocrine therapy with the LHRH-analogue Zoladex, tamoxifen, Zoladex plus tamoxifen, versus no adjuvant endocrine therapy.
• The treatment duration was 2 years.
• No adjuvant chemotherapy was used.
• TBBM was measured using dual photon X-ray absorptiometry.
• Measurements were made before initiation of treatment, at 12 months, at 24 months and at 36 months, that is, about 1 year after cessation of treatment.

Results:

Results concerning TBBM in relation to the base- line value were calculated. The 12 month baseline changes in TBBM were as follows:
• Allocated treatment 12 months (%)
• Controls 99.6 p= .66
• Tamoxifen 98.5 p<0.01
• Tamoxifen and Zoladex 98.8 p < 0.02
• Zoladex 95 p < 0.001
When evaluated again at 36 months the Zoladex alone group had a change from baseline TBBM of 101.5%. This indicated that the patients on Zoladex alone had remineralized their bones after a one year cessation of the drug.

Authors' Conclusions

The study authors' conclude that 2 years of chemical ovarian ablation causes a significant reduction in bone mineral content (p<0.001) but there is no indication of progressive loss one year after cessation of treatment. The addition of tamoxifen to Zoladex appears to compensate for the demineralizing effects of Zoladex.

Clinical/Scientific Implications:

This small but well-done study, gives us insight into the risk of bone loss with adjuvant endocrine therapy in premenopausal women. As demonstrated in retrospective reviews, the addition of tamoxifen to an LHRH-analogue (like Zoladex) helps to neutralize bone demineralizing effects associated with the chronic use of LHRH- analogues.