Estrogen Receptor Beta (ER-β) as a coadjuvant target of neoadjuvant endocrine therapy
| ISRCTN | ISRCTN89801719 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN89801719 |
| Protocol serial number | N/A |
| Sponsor | Federal University of Sao Paulo (Brazil) |
| Funder | Federal University of Sao Paulo (UNIFESP) - Senology Discipline, Department of Gynecology (Brazil) |
- Submission date
- 26/01/2013
- Registration date
- 06/02/2013
- Last edited
- 27/06/2014
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
The role of estrogen receptor beta (ER-β) in human breast cancer remains unclear. There is no consensus regarding the clinical utility of an ER-β assay. Some studies have suggested that ER-β may oppose the actions of estrogen receptor alpha (ER-α), and clinical evidence has indicated that the loss of ER-β expression is associated with a poor prognosis and resistance to endocrine therapy. The objective of the present study is to determine the role of ER-β and the ER-α/ER-β ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-α and ER-β expression levels.
Who can participate?
Postmenopausal women with histologically confirmed invasive breast cancer without previous treatment for the disease (surgery, radio or chemotherapy).
What does the study involve?
Patients with operable breast cancers will be randomly allocated to one of three groups: receive 26 days of treatment with anastrozole (1 mg/day), tamoxifen (20 mg/day) or placebo. The pre- and post-hormone therapy samples will be placed in tissue microarray blocks and submitted to immunohistochemical assay. Biomarker statuses (ER-β, ER-α and Ki67) will be obtained by comparing each immunohistochemical evaluation of the pre- and post-surgery samples using the semi-quantitative Allred´s method.
What are the possible benefits and risks of participating?
There will be no immediate direct benefit to those taking part. A treatment period of 26 days was chosen for this study because this is the average time needed to complete routine preoperative testing in most Brazilian institutions, justifying the use of placebo without negative consequences to the patients. In addition, the period of drug exposure is too short to observe the most important side effects of treatment in the anastrozole and tamoxifen groups.
Where is the study run from?
Two centres are taking part in this study. Patients will be recruited at Pérola Byington Hospital, Sao Paulo / Brazil and Federal University of Sao Paulo Hospital, Sao Paulo / Brazil.
When is the study starting and how long is it expected to run for?
The study started in October 2010 and will run for 36 months or until the required number of 90 patients have been recruited and evaluated.
Who is funding the study?
Senology Discipline, Department of Gynecology, Federal University of Sao Paulo UNIFESP (Brazil)
Who is the main contact?
Marcelo Madeira
marcemadeira@gmail.com
Contact information
Scientific
R. Sampaio Viana, 580
Sao Paulo
04004-002
Brazil
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised prospective controlled double-blind study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Estrogen Receptor Beta (ER-β) as a predictor of endocrine therapy responsiveness A randomised neoadjuvant trial comparison between Anastrozole and Tamoxifen for the treatment of postmenopausal breast cancer |
| Study objectives | Several studies have suggested that the expression of ER-β independently predicts a better disease-free survival in breast cancer patients. Our hypothesis is that the measurement of ER-β or the ratio of ER-α/ER-β expression in breast cancer patients may help predict tamoxifen and anastrozole responsiveness in the neoadjuvant therapy. |
| Ethics approval(s) | Human Investigation Committees of Federal University of São Paulo (UNIFESP) and Pérola Byington Hospital, 30-Jul-2010, ref: CEP0894/10 (Brazil) |
| Health condition(s) or problem(s) studied | Breast Cancer |
| Intervention | Patients with operable breast cancers will receive orally treatment with anastrozole (1 mg/day), tamoxifen (20 mg/day) or placebo during 26 days. |
| Intervention type | Drug |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Anastrazole, tamoxifen |
| Primary outcome measure(s) |
To determine the role of ER-β in predicting the response to breast cancer therapy with anastrozole and tamoxifen we will observe the expression of Ki67 (cell proliferation marker) in tumor biopsy samples taken before and after treatment (26 days) of ER-β-positive and ER-β-negative breast cancer patients. |
| Key secondary outcome measure(s) |
The ER-α/ER-β expression ratio predicting the response to breast cancer endocrine therapy and whether different regimens of treatment have any effect on ER-α and ER-β expression levels. |
| Completion date | 29/10/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 90 |
| Key inclusion criteria | Histologically confirmed invasive breast cancer in women who were postmenopausal, which is defined as no menstruation periods over the last 12 months and/or an FSH level within the postmenopausal range. |
| Key exclusion criteria | 1. The presence of endocrine disease, metastatic disease, inflammatory breast cancer (T4d) 2. History of thromboembolism 3. Use of hormone replacement therapy (HRT) or previous treatment for breast cancer (surgery, radio or chemotherapy). Patients who do not comply with the prescribed medication regimen or postpone surgery are also excluded from the study. Patients who had previously taken HRT may be included if they have stopped hormonal treatment at least six months prior to trial randomisation. |
| Date of first enrolment | 29/10/2010 |
| Date of final enrolment | 29/10/2013 |
Locations
Countries of recruitment
- Brazil
Study participating centre
04004-002
Brazil
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 18/09/2013 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
