Clinical trial NCT00949598: Letrozole or Tamoxifen Citrate in Treating Older Postmenopausal Women Undergoing Surgery for Breast Cancer
Official title: Randomized Double-blind Study to Compare Two Neo-adjuvant Treatments: an Anti-aromatase vs SERM for Postmenopausal Women With ER+ Breast Adenocarcinoma: Effect on Intermediate Predictive Biological Response to Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: estrogen receptor-positive breast cancer
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2009-07-30
Enrollment: 177
Sex: FEMALE
Minimum age (years): 65
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the uptake of estrogen. Tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether letrozole or tamoxifen citrate is more effective when given before surgery in treating older women with breast cancer.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with tamoxifen citrate in treating older postmenopausal women undergoing surgery for breast cancer.

Detailed description: OBJECTIVES:

Primary

* Investigate the changes in Ki67 and PCNA in postmenopausal women with estrogen receptor-positive (ER+) breast cancer after 4 months of treatment with letrozole vs tamoxifen citrate.

Secondary

* Compare the response after 4 months of therapy.
* Define the resistant forms of cancer in patients treated with these regimens.
* Define the molecular signature predictive of sensitivity or resistance to ER+ breast adenocarcinoma by gene and serum protein profiling.
* Search for serum protein profiles predictive of recurrence-free interval.

OUTLINE: Patients are randomized into 1 of 2 intervention arms.

* Arm I: Patients receive oral letrozole once daily for 16 weeks.
* Arm II: Patients receive oral tamoxifen citrate once daily for 16 weeks. Patients in both arms then undergo surgery.

Blood and tumor tissue samples are collected at baseline and after completion of neoadjuvant therapy for changes in Ki67 and PCNA and serum protein profiling analysis.

After completion of study therapy, patients are followed up every 6 months for 3 years, and then once a year for 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed invasive breast adenocarcinoma

  * Clinically T2 tumor and/or \> 1 cm by echography
  * Estrogen receptor (ER)-positive and \> 10% of the tumor cells positive

    * No ER-negative disease
* No prior breast cancer
* No metastatic or inflammatory breast adenocarcinoma

PATIENT CHARACTERISTICS:

* Postmenopausal
* No cardiac function that could contraindicate surgery or medical treatment (e.g., radiotherapy and/or chemotherapy)
* No prior malignancies within the past 5 years except for nonmelanoma skin cancer or carcinoma in situ of the cervix
* No mental incapacitation that would preclude consent
* No contraindication to tamoxifen citrate or letrozole

PRIOR CONCURRENT THERAPY:

* More than 8 days since prior hormone-replacement therapy or other treatment (i.e., phytoestrogen) for menopause
* No concurrent therapy that would modify the expression of the genes regulated by estrogen
* No concurrent participation in another clinical study

Primary outcomes:
measure: Changes in Ki67 and PCNA after 4 months of treatment with letrozole vs tamoxifen citrate
timeFrame: up to 24 months
Secondary outcomes:
measure: Molecular signature predictive of sensitivity or resistance to estrogen receptor-positive breast adenocarcinoma
timeFrame: up to 24 months
measure: Survival rate
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Philippe Rouanet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: