Pre-operative Hormonal Treatment for Hormone Receptor Positive Breast Cancer

Study Overview
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Brief Summary
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To investigate prospectively whether short term endocrine treatment can induce molecular changes, predictive for therapy response.

Detailed Description
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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.

Official Title
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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).

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Anastrozole
* Drug: Anastrozole+Fulvestrant
* Drug: Tamoxifen
* Drug: Tamoxifen


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Anastrozole | Drug: Anastrozole<br>* 1 mg,QD,PO<br>|
| Experimental: 2<br>Anastrozole + Fulvestrant | Drug: Anastrozole+Fulvestrant<br>* Anastrozole; 1 mg, QD, PO Fulvestrant; 500 mg, IM, day 1, 15, 29 and monthly thereafter<br>|
| Active Comparator: 3<br>Tamoxifen | Drug: Tamoxifen<br>* loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO<br>|
| Other: 4<br>Tamoxifen (pre-menopausal and male patients) | Drug: Tamoxifen<br>* loading dose of 40 mg, TID, PO, during 7 days, Thereafter 20 mg, QD, PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in tumor cell proliferation and induced apoptosis. |  | At baseline and after 2-6 weeks of endocrine treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of changes in gene expression after different endocrine treatment exposures |  | At baseline and after endocrine treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre-operative, endocrine treatment, drug resistance