Clinical trial NCT00966043: Prevalence of Genetic Polymorphisms in Genes Coding for Tamoxifen Metabolising Enzymes
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Neoplasms
Lead sponsor: Vlaamse Vereniging voor Obstetrie en Gynaecologie
Sponsor class: OTHER
First posted: 2009-08-26
Enrollment: 158
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Postmenopausal female breast cancer patients starting adjuvant tamoxifen therapy.

Brief summary: CYPTAM-BRUT 3 is a prospective, multicentric study in Belgium within the CYPTAM study of the Leiden University Medical Center (NTR1509) including postmenopausal women receiving tamoxifen for estrogen-receptor positive breast cancer in the adjuvant setting. The primary endpoint is the difference in uterine changes between women with a normal versus low TAS after 3 months of tamoxifen use. Secondary endpoints are serum metabolite concentrations, serum follicle-stimulating hormone level, serum sex hormone-binding globulin level and menopausal symptoms. These patients are registered in the Leiden protocol with time to breast cancer event as primary endpoint.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: change in endometrial thickness or uterine volume
timeFrame: 3-6 months
Secondary outcomes:
measure: Tolerability of tamoxifen-HRQoL questionnaire
timeFrame: 3-6 months
measure: Vaginal bleeding
timeFrame: 3-6 months
measure: Biochemical changes
timeFrame: 3-6 months
Other outcomes:
Locations:
city: Duffel
country: Belgium
facility: AZ St-Maarten
state: Antwerpen
city: St-Niklaas
country: Belgium
facility: AZ St-Nikolaas
state: Antwerpen
city: Genk
country: Belgium
facility: Ziekenhuizen Oost-Limburg Camus St-Jan
state: Limburg
city: Dendermonde
country: Belgium
facility: AZ St-Blasius
state: Ookst-Vlaanderen
city: Gent
country: Belgium
facility: Maria-Middelares
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: UZ
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ
state: Vlaams-Brabant
city: Roeselare
country: Belgium
facility: Heilig-Hart Ziekenhuis
state: West-Vlaanderen
city: Brussel
country: Belgium
facility: Institut Bordet
city: Brussel
country: Belgium
facility: UZ
city: Brussel
country: Belgium
facility: UCL
Study officials:
affiliation: UZ Leuven
name: Patrick Neven
role: PRINCIPAL_INVESTIGATOR
References: