Tamoxifen Resistance in Women With Stage I, Stage II, Stage IIIA, or Stage IIIB Breast Cancer

Tamoxifen Resistance in Breast Cancer

RATIONALE: Studying samples of blood from patients with breast cancer in the laboratory may help doctors identify and learn more about biomarkers related to tamoxifen resistance.

PURPOSE: This laboratory study is looking at tamoxifen resistance in women with stage I, stage II, stage IIIA, or stage IIIB breast cancer.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Drug: tamoxifen citrate

Detailed Description

OBJECTIVES:

• Identify women who are resistant to tamoxifen citrate and other drugs for the treatment of breast cancer by testing their plasma for the presence of proteins (e.g., macrophage migration inhibition factor) encoded by resistance-inducing genes (RIGs).
• Provide retrospective data on the predictive value of RIGs to serve as the basis for a prospective clinical trial of these genes as predictors of drug resistance.

OUTLINE: This is a multicenter study. Patients are stratified according to response during tamoxifen citrate (TAM) therapy (resistant group [i.e., those who develop recurrent breast cancer while being treated with TAM] vs conditionally sensitive group [i.e., those who have disease-free survival for over 3 years after initial diagnosis while being treated with TAM]).

Patients undergo blood collection at baseline, within 3 weeks of initiation of TAM therapy, and then every 6 months for 3 years or until relapse, whichever comes first. Samples are analyzed by enzyme-linked immunosorbent assay for expression of protein biomarkers (i.e., kallikrein gene 10, macrophage migration inhibition factor, prolyl carboxypeptidase, queuine tRNA-ribosyltransferase, and kinesin) encoded by resistance-inducing genes. An additional blood sample is obtained from patients at the time of relapse, if available.

Patients also undergo assessment of medical history, personal habits, and characteristics of breast cancer (e.g., tumor histology, stage, and grade) at baseline.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Female >/= 18 years old with confirmed invasive breast cancer

Description

Inclusion Criteria:

• Histologically confirmed invasive breast cancer

  • Initial pathologic stage I-IIIB disease
  • No stage IV disease

• Meets the following criteria for breast cancer therapy:

  • Received prior primary local therapy for breast cancer
  • Scheduled to begin tamoxifen citrate as adjuvant therapy for breast cancer within 3 weeks

• Hormone receptor status:

  • Estrogen-receptor positive tumor
• Female
• Pre- or post-menopausal
• Must be able to donate 20 mL of blood

Exclusion Criteria:

• Severe anemia, defined as hemoglobin < 11 g/dL
• Psychiatric history that would preclude obtaining informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Evaluation of the mechanisms of tamoxifen citrate (TAM) resistance in breast cancer
Change in expression levels of protein biomarkers of TAM resistance as measured periodically for 3 years or until relapse, whichever comes first
Retrospective data on the predictive value of resistance-inducing genes

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Steven A. Akman, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: CDR0000547204; P30CA012197 (U.S. NIH Grant/Contract); CCCWFU-74B07; CCCWFU-IRB00002657

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No