Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

• Invasive disease-free survival (DFS) of women with node-positive breast cancer treated with endocrine therapy with vs without chemotherapy [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  Defined as the time from the second registration (randomization) to local, regional, or distant recurrence, new invasive primary, or death due to any cause. The STEEP definition of invasive disease-free survival (IDFS) is used, although it is referred to here by the more common acronym DFS. Survival times are censored at time of last follow-up for individuals who did not have any event meeting the above definition.
  
  

• Overall survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  Defined as the time from the second registration (randomization) to death due to any cause. Survival times are censored at time of last follow-up for individuals who are not known to have died.
  
  
• Distant DFS [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  Defined as the time from second registration to distant recurrence, new invasive primary, or death due to any cause. Patients who have local or regional recurrence are continued to be followed for a distant event or death. Survival times are censored at time of last follow-up for individuals who are not known to have died and have not had a distant recurrence or new primary.
  
  
• Local disease-free interval [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  Defined as the time from second registration to local/regional recurrence. Patients who have distant recurrence or a new primary or who die without recurrence are censored at time of this event. The analysis of this endpoint must account for informative censoring using a competing risk framework. Survival times are also censored at time of last follow-up for individuals who are not known to have died and have had a recurrence or new primary.
  
  
• Toxicities using standard NCI-CTCAE version 4.0 [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
  

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.