PRIMARY OBJECTIVES:

I. To determine the effect of endocrine therapy with versus without chemotherapy in patients
with node-positive breast cancer who do not have high Recurrence Scores (RS) by Oncotype
DX®.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS), distant disease-free survival (DDFS), and local
disease-free interval (LDFI) by receipt of chemotherapy or not and its interaction with RS.
II. To compare the toxicity across the treatment arms. III. To perform other assays or tests
(in particular the PAM50 risk of relapse score) as they are developed and validated that
measure potential benefit of chemotherapy and compare them to Oncotype DX®.

IV. To determine the impact of management with Oncotype DX® on patient-reported anxiety
(co-primary Health-Related Quality of Life [HRQL] outcome) prior to screening, after
disclosure of test results, and during the randomized trial.

V. To determine the impact of Oncotype DX® on the initial management cost of node-positive,
HR-positive, HER2-negative breast cancer.

VI. To compare patient-reported utilities (e.g., QOL) for those randomized to chemotherapy
versus no chemotherapy.

VII. To estimate the cost-effectiveness of management with Oncotype DX® vs usual care using
modeling and DFS information from the trial.

VIII. To determine the role of other assays (e.g., PAM50) as predictors of DFS, DDFS, and
LDFI of patients randomized to chemotherapy versus no chemotherapy.

IX. To determine the impact of treatment with chemotherapy versus no chemotherapy on
patient-reported fatigue and cognitive concerns (secondary HRQL outcomes).

X. To determine the impact of management with Oncotype DX® on patient-reported decision
conflict, perceptions regarding Oncotype DX® testing, and survivor concerns prior to
screening, after disclosure of test results, and during the randomized trial (secondary HRQL
outcomes).

OUTLINE: This is a multicenter study. Patients are stratified according to Recurrence Score
(0-13 vs 14-25), menopausal status (pre-menopausal vs post-menopausal), and type of nodal
dissection (axillary lymph node dissection [with or without sentinel node mapping] vs
sentinel node biopsy without axillary lymph node dissection). Patients are randomized to 1
of 2 treatment arms.

ARM I: Patients receive a protocol-approved chemotherapy regimen based on the patient and/or
physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy
comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or
exemestane), or both for 5-10 years in the absence of disease progression or unacceptable
toxicity.

ARM II: Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate,
an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in
the absence of disease progression or unacceptable toxicity.

Patients may complete health-related quality-of-life (QOL) questionnaires at baseline and
periodically during study. Information on Medicare and/or insurance coverage and on health
coverage decisions may also be collected periodically.

After completion of study therapy, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then yearly for at least 15 years.