Condition category
Cancer
Date applied
26/01/2013
Date assigned
06/02/2013
Last edited
27/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Mr Marcelo Madeira

ORCID ID

Contact details

R. Sampaio Viana
580
Sao Paulo
04004-002
Brazil

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

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

Acronym

Study hypothesis

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

Human Investigation Committees of Federal University of São Paulo (UNIFESP) and Pérola Byington Hospital, 30-Jul-2010, ref: CEP0894/10 (Brazil)

Study design

Randomised prospective controlled double-blind study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please contact marcemadeira@gmail.com or mattar.andre@gmail.com to request a patient information sheet

Condition

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 names

Anastrazole, tamoxifen

Primary outcome measures

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.

Secondary outcome measures

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.

Overall trial start date

29/10/2010

Overall trial end date

29/10/2013

Reason abandoned

Eligibility

Participant 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.

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

90

Participant 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.

Recruitment start date

29/10/2010

Recruitment end date

29/10/2013

Locations

Countries of recruitment

Brazil

Trial participating centre

R. Sampaio Viana, 580
Sao Paulo
04004-002
Brazil

Sponsor information

Organisation

Federal University of Sao Paulo (Brazil)

Sponsor details

Senology Discipline
Department of Gynecology
R. Botucatu
740
Sao Paulo
04023-900
Brazil

Sponsor type

University/education

Website

http://www.unifesp.br

Funders

Funder type

University/education

Funder name

Federal University of Sao Paulo (UNIFESP) - Senology Discipline, Department of Gynecology (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24047421

Publication citations

  1. Results

    Madeira M, Mattar A, Logullo AF, Soares FA, Gebrim LH, Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness-a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer., BMC Cancer, 2013, 13, 425, doi: 10.1186/1471-2407-13-425.

Additional files

Editorial Notes