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

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.

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