S8814A Biomarkers in Predicting Outcome in Postmenopausal Women With Hormone Receptor-Positive, Node-Positive Breast Cancer Treated With Tamoxifen With or Without Cyclophosphamide, Doxorubicin, and Fluorouracil

Breast Cancer Clinical Trial

Official title:

Molecular Predictors of Outcome on CAF Plus Tamoxifen Versus Tamoxifen Alone in Postmenopausal Women With Node Positive, Receptor Positive Breast Cancer [NCI Correlative Science Reference No. # 8814A-ICSC]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00897091
• Other study ID #: CDR0000528264
• Secondary ID: S8814A-ICSCGHI-0
• Status: Completed
• Phase: N/A
• First received: May 9, 2009
• Last updated: May 28, 2013
• Start date: July 2006
• Est. completion date: October 2007

Study information

• Verified date: May 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This laboratory study is looking at biomarkers in predicting outcome in postmenopausal women with hormone receptor-positive, node-positive breast cancer treated with tamoxifen with or without cyclophosphamide, doxorubicin, and fluorouracil.

Description:

OBJECTIVES:

Primary

• Determine the value of the Oncotype DX Recurrence Score for prediction of treatment benefit of cyclophosphamide, doxorubicin hydrochloride, and fluorouracil (CAF) chemotherapy, in terms of disease-free survival (DFS) and overall survival (OS), in postmenopausal patients with estrogen and/or progesterone receptor-positive, node-positive breast cancer treated on clinical trial SWOG-8814.

• Determine the overall prognostic value of the Oncotype DX Recurrence Score, in terms of DFS and OS, in patients treated with tamoxifen citrate alone or CAF with concurrent or sequential tamoxifen citrate.

Secondary

• Determine the optimal cut point (i.e., low, intermediate, and high recurrence risk) for the Recurrence Score in these patients.

• Determine the relationship between expression of any one of the 21 genes on the Oncotype DX gene panel with DFS and OS.

• Determine whether the expression of any of these genes are associated with CAF treatment benefit.

• Determine the relationship between the Oncotype DX Recurrence Score and DFS and OS in multivariate models, including number of positive nodes, tumor size, tumor grade, estrogen receptor, progesterone receptor, and HER2 and p53 status.

• Determine the relationship between quantitative reverse-transcriptase-polymerase chain reaction expression of up to 800 additional genes and prognosis and/or prediction of CAF benefit.

OUTLINE: This is a multicenter study.

Fixed paraffin-embedded breast tumor tissue samples (obtained from the SWOG Central Tumor Repository at the University of Colorado) are analyzed by the Oncotype DX panel containing the following 21 genes: BAG1, Bc12, CCNB1, CD68, SCUBE2, CTSL2, Esrt1, GRB7, GSTM1, HER2, Ki-67, MYBL2, PR, STK15, STMY3, SURV, B-actin, GAPDH, GUS, RPLPO, and TFRC. The Oncotype DX Recurrence Score is calculated for each patient. Analyses are performed to determine the relationship between the Recurrence Score and gene expression and prognosis/prediction of therapy (tamoxifen citrate alone or cyclophosphamide, doxorubicin hydrochloride, and fluorouracil with concurrent or sequential tamoxifen citrate) benefit as well as to determine the relationship between clinical and demographic covariates and disease-free and overall survival.

Samples are also analyzed by reverse-transcriptase-polymerase chain reaction for exploratory analysis of up to 800 additional genes that may be prognostic and/or predict the likelihood of therapy benefit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 750
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Node-positive disease (pT1-3a, pN1-2 [clinical N0-1], M0)

• Previously enrolled in SWOG-8814, a treatment clinical trial, and in SWOG-9445, a companion tissue banking study

• Tumor block or unstained sections available from initial diagnosis in the SWOG archive

• Sufficient tumor in block or unstained sections

• Patients for whom only unstained slides are available must have acceptable reverse-transcriptase-polymerase chain reaction (RT-PCR) profiles

• Sufficient RNA (= 300 ng) for RT-PCR analysis with the Oncotype DX 21 gene assay

• Average normalized cycle threshold for the 5 reference genes = 35

• Follow-up data from the SWOG-8814 clinical trial obtained from the patient

• Hormone receptor status:

• Estrogen and/or progesterone receptor positive tumor

PATIENT CHARACTERISTICS:

• Female

• Postmenopausal

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Time Perspective: Retrospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Genetic:
• comparative genomic hybridization

• microarray analysis

• reverse transcriptase-polymerase chain reaction

Other:
• diagnostic laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival			No
Primary	Overall survival			No
Secondary	Distant disease-free recurrence			No

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database