A randomized, prospective trial of 3 weeks pre-operative hormonal treatment for hormone receptor positive breast cancer: Anastrozole, Fulvestrant or Tamoxifen Exposure - Response in molecular profile (AFTER).

Phase 2

Conditions: breast cancer
mammary neoplasms
10006291

Registration Number: NL-OMON41277

Lead Sponsor: ederlands Kanker Instituut

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 250

Inclusion Criteria

• Patients with proven invasive adenocarcinoma of the breast
• Any tumor with a size >= 1cm (NOT inflammatory breast cancer)
Patients with a tumor diameter > 0.5 and < 1.0 cm are eligible when a biopsy can be performed, however for very small tumors leaving behind a radiologic marker need to be discussed.
• 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 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change in tumor cell proliferation. Proliferation will be measured by (change<br /><br>in) Ki67 expression and Cyclin A, apoptosis by the TUNEL assay. We will try to<br /><br>correlate the TAMRO-profile, the phospho-PKA expression, and the<br /><br>phosphorylation extent of Serine305 with these parameters.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Investigate different gene-profiles with proven predictive value for<br /><br>endocrine resistance<br /><br>• Compare the changes in gene expression in the different study arms with<br /><br>changes in proliferation index<br /><br>• To collect blood samples of all patients for research on SNPs in CYP450<br /><br>sequences in normal and tumor DNA.<br /><br>• To collect tumor material for research on downregulation of ER and PgR.<br /><br>• To collect blood samples to evaluate whether (a change in) estrogen serum<br /><br>levels correlate with outcome.<br /><br>• To study the relationship among concentrations of tamoxifenmetabolites in<br /><br>serum and tumormaterial and expression levels of CYP450 sequences in the tumor.<br /><br>- Investigate paired tumor samples by ChIP-sequencing for response-predicting<br /><br>changes in estrogen-receptor binding sites<br /><br>- To collect blood samples to evaluate the effect of endocrine therapy on the<br /><br>immune system.</p><br>