Bone Mineral Density In Premenopausal Patients In A Randomized Trial Of Adjuvant Endocrine Therapy (ZIPP-TRIAL)
Heather Jones, MD
University of Pennsylvania Cancer
Ultima Vez Modificado: 15 de mayo del 2001
Presenter: Asgerdur Sverrisdóttir Affiliation: University Hospital, Stockholm, Sweden
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 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.
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.
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.
Nov 2, 2010 - Most recent oncology randomized controlled trials evaluate drugs that are available "off-protocol therapy" in the United States, and this can adversely impact trial enrollment, according to a study published online Oct. 25 in the Journal of Clinical Oncology.