Letrozole or Tamoxifen Citrate in Treating Older Postmenopausal Women Undergoing Surgery for Breast Cancer

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.

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: tamoxifen citrate; Drug: letrozole

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.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral letrozole once daily for 16 weeks.	Drug: letrozole; Given orally
Experimental: Arm II; Patients receive oral tamoxifen citrate once daily for 16 weeks.	Drug: tamoxifen citrate; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in Ki67 and PCNA after 4 months of treatment with letrozole vs tamoxifen citrate	up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Molecular signature predictive of sensitivity or resistance to estrogen receptor-positive breast adenocarcinoma	up to 24 months
Survival rate	up to 24 months

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Principal Investigator: Philippe Rouanet, MD, PhD, Institut du Cancer de Montpellier - Val d'aurelle

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: July 29, 2009
• First Submitted That Met QC Criteria: July 29, 2009
• First Posted (Estimated): July 30, 2009

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage II breast cancer; stage IA breast cancer; stage IB breast cancer; estrogen receptor-positive breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Bone Density Conservation Agents; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen
• Other Study ID Numbers: CDR0000638373