Prevalence of Genetic Polymorphisms in Genes Coding for Tamoxifen Metabolising Enzymes, in Postmenopausal ER-positive Breast Cancer Patients According to Uterine and Biochemical Changes and Tolerability of Tamoxifen.
18 Years
N/A
Female
Breast Neoplasms, Female
Trial Information
Prevalence of Genetic Polymorphisms in Genes Coding for Tamoxifen Metabolising Enzymes, in Postmenopausal ER-positive Breast Cancer Patients According to Uterine and Biochemical Changes and Tolerability of Tamoxifen.
We will study the impact of the 'tamoxifen activity score' - based on functional genetic
polymorphisms for tamoxifen metabolism and the use of drugs that interfere with
tamoxifen-against tamoxifen related endpoints like uterine changes and subjective menopausal
symptoms.
The prevalence of genetic polymorphisms in the CYP2D6 and other genes and differences in
usage of drugs interacting with tamoxifen metabolism will be compared between women with and
those without endometrial thickening on one hand and between women with and those without
hot flashes on the other hand. Tamoxifen use in adjuvant setting.
- "Tamoxifen activity score" (23): The endpoints will be correlated with a predefined
'tamoxifen activity score' which is based on the presence of single nucleotide
polymorphisms (SNP) in relevant genes combined with the effect of well known drugs that
interfere with the metabolism of tamoxifen. The 'tamoxifen activity score' has been
associated with tamoxifen compliance by a group in the US (23). The score will be
adapted to the Belgian situation based on the prevalence of these SNPs in a Belgian
population of volunteers for blood donation and consecutive breast cancer patients.
- The study setting are postmenopausal women with an early ER- positive breast cancer and
not previously treated with an endocrine agent or hormone replacement therapy, with an
intact uterus and clearly measurable thin endometrium/uterus. N =250
Inclusion Criteria:
- Female > 18 years of age
- Written and voluntary informed consent understood signed and dated
- Histologically or cytologically confirmed measurable invasive adenocarcinoma of the
breast, amenable to curative therapy.
- Patients must be postmenopausal as defined by criteria in appendix 1.
- Breast cancer should be considered as oestrogen receptor positive by the clinician
using immunohistochemistry readings as is standard procedure for local pathologist
- Prior endocrine tamoxifen therapy is not allowed
- Patients are not previously treated with an endocrine agent or hormone replacement
therapy needs being stopped for at least 6 months.
- Prior chemotherapy and radiotherapy is allowed
- Adequate renal and liver function Serum creatinine and serum bilirubin ≤ 1.5 X ULN
Serum ALT and AST ≤ 2.5 X ULN (or ≤ 5 in case of liver metastases)
- Serum calcium should be ≤ 11,6 mg/dl
- ECOG performance status 0,1,2 (appendix 2)
Exclusion Criteria:
- Male
- Life threatening disease requiring a quick response (eg, extensive hepatic or
pulmonary involvement)
- Use of any endocrine treatment or recent/current use of hormone replacement therapy.
- Contra indication for tamoxifen: history of DVT/vaginal bleeding of unknown origin
- Dementia
- History of other malignancy that may interfere with at least 6 months of tamoxifen
therapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
change in endometrial thickness or uterine volume
Outcome Time Frame:
3-6 months
Safety Issue:
No
Principal Investigator
Patrick Neven
Investigator Role:
Principal Investigator
Investigator Affiliation:
UZ Leuven
Authority:
Belgium: Federal Agency for Medicinal Products and Health Products
Study ID:
Eudract 2009-010059-28.
NCT ID:
NCT00966043
Start Date:
June 2009
Completion Date:
December 2010
Related Keywords:
- Breast Neoplasms
- Female
- Breast Neoplasms
- Neoplasms
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