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Molecular profiling of post-menopausal women with breast cancer on Neoadjuvant Endocrine Therapy with tamoxifen or exemestane

Completed
Conditions
Breast cancer
ocalised or locally advanced early breast cancer
Cancer
Registration Number
ISRCTN87408408
Lead Sponsor
Cambridge University Hospitals NHS Trust (UK)
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Female
Target Recruitment
100
Inclusion Criteria

1. Women with histological diagnosis of primary invasive breast cancer on core biopsy
2. Not a candidate for chemotherapy
3. Localised or locally advanced breast cancer
4. Ultrasound size at least 2 cm:
a. unifocal tumour:
i. T2 or T3 tumours (radiological size more than 20 mm)
ii. T4 tumour of any size with direct extension to either chest wall or skin
iii. inflammatory carcinoma with tumour of any size
OR
b. other locally advanced disease:
i. clinical and radiological involvement of axillary lymph node (radiological diameter more than 20 mm) and primary breast tumour of any diameter
ii. where no primary breast tumour was found, the presence of breast cancer in a Lymph Node (LN) must be histopathologically confirmed by LN biopsy (Tru-cut or whole LN)
OR
c. multifocal tumour:
i. the sum of the tumour diameters must be more than 20 mm (radiological size more than 20 mm)
ii. patients with bilateral disease are eligible to enter the trial
iii. no previous treatment for breast cancer
5. Oestrogen Receptor (ER) positive (Allred score more than or equal to four)
6. Palpable and measurable disease in the breast or axilla
7. Post-menopausal defined by following criteria: cessation of menstrual periods for at least 1 year or bilateral surgical oophorectomy or Follicular Stimulating Hormone (FSH) and oestradiol in the post-menopausal range
8. At least 2 weeks since prior hormone replacement therapy or phyto-oestrogens herbal, alternative, or Over-The Counter (OTC) sex hormone remedies and not on concomitant hormonal therapy with these agents
9. Eastern Cooperative Oncology Group (ECOG) performance status zero, one or two
10. Randomisation and treatment within 4 weeks of biopsy
11. Patient must have adequate bone marrow, hepatic and renal function
12. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
13. Written consent for the trial

Exclusion Criteria

1. Patient unfit to receive endocrine-based therapy
2. Previous history of cancer excluding basal cell carcinoma, cervical carcinoma in-situ, or ductal carcinoma in situ of the breast
3. Previous deep vein thrombosis or pulmonary embolism

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Identify molecular markers that would predict the response or resistance to endocrine therapy with exemestane or tamoxifen.
Secondary Outcome Measures
NameTimeMethod
1. Clinical Response Rate (cRR)<br>2. Radiological Response Rate (rRR)<br>3. Changes in Ki67 counts in response to therapy<br>4. Clinical/radiological response among patients over-expressing Epidermal Growth Factor Receptor (EGFR)/Human Epidermal growth factor Receptor 2 (HER-2)<br>5. Serum levels of Vascular Endothelial Growth Factor Receptors (VEGF-R) and Vascular Endothelial Growth Factor (VEGF) before, during and after treatment<br>6. Serum circulatory HER-2 Extracellular Domain (ECD) and Circulating Endothelial Cells (CEC) changes during treatment<br>7. Vascular Endothelial Growth Factor A (VEGFA), Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) expression and correlation with clinical outcomes<br>8. Cadherin-11, transcription factor (Activating Protein?1 [AP-1], Ets-2, cyclin D1)<br>9. Gene profiling to identify molecular markers of response or resistance
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