Clinical trial NCT00738777: Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer
Official title: A Randomized, Prospective Trial of 2-6 Weeks Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer: Anastrozole +/- Fulvestrant or Tamoxifen Exposure - Response in Molecular Profile (AFTER-study).
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: pre-operative
endocrine treatment
drug resistance
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2008-08-20
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.

Detailed description: We will perform a randomized, open-label, single-institution study. It will compare the efficacy of three different endocrine treatment regimens (Anastrozole +/- Fulvestrant or Tamoxifen) in changing proliferation-index and inducing apoptosis during a 2-6 week pre-operative treatment period in breast cancer patients. These results will be correlated to gene expression profiles, phosphorylation status of the ER, SNPs in CYP450 sequences, tamoxifen metabolite concentrations, changes in estrogen serum levels and protein expression patterns.

Eligibility criteria: Inclusion Criteria:

* Patients with proven invasive adenocarcinoma of the breast
* Any tumor with a size ≥ 1cm (NOT inflammatory breast cancer)
* WHO-performance score 0 or 1
* Written informed consent

Exclusion Criteria:

* Clues of metastatic disease by clinical examination according to most recent NABON guidelines
* Multicentric breast cancer
* Inflammatory breast cancer
* Hormone replacement during the last 12 months
* Other systemic treatment during the waiting time till surgery
* Already planned date for surgery within the next 2 weeks
* Any psychological, familial, sociological or geographical condition potentially hampering adequate informed consent or compliance with the study protocol
* Patient's refusal to undergo a core biopsy procedure of the primary tumor before the start of treatment

NB: a concomitant malignancy within the last five years is not an exclusion criterium, because survival is not the primary endpoint. Just as prior invasive breast cancer or DCIS within the last 15 years is not an exclusion criterium.

NB: Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during the study.

Primary outcomes:
measure: Decrease in tumor cell proliferation and induced apoptosis.
timeFrame: At baseline and after 2-6 weeks of endocrine treatment
Secondary outcomes:
measure: Comparison of changes in gene expression after different endocrine treatment exposures
timeFrame: At baseline and after endocrine treatment
Other outcomes:
Locations:
city: den Haag
country: Netherlands
facility: Medisch Centrum Haaglanden
state: ZH
city: Amsterdam
country: Netherlands
facility: NKI-AVL
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis
city: Nijmegen
country: Netherlands
facility: UMC St. Radboud
Study officials:
affiliation: NKI-AvL
name: Sabine C Linn, MD
role: PRINCIPAL_INVESTIGATOR
References: