Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

PRIMARY OBJECTIVES: I. To determine whether adjuvant hormonal therapy is not inferior to adjuvant chemohormonal in women whose tumors meet established clinical guidelines for adjuvant chemotherapy and fall in the "primary study group" category (Oncotype DX Recurrence Score 11-25). II. To create a tissue and specimen bank for patients enrolled in this trial, including formalin fixed paraffin embedded tumor specimens, tissue microarrays, plasma, and deoxyribonucleic acid (DNA) obtained from peripheral blood. SECONDARY OBJECTIVES: I. To determine whether adjuvant hormonal therapy is sufficient treatment (i.e. 10 year distant disease-free survival of at least 95%) for women whose tumors meet established clinical guidelines for adjuvant chemotherapy and who fall into the "Secondary Study Group-1" category (Oncotype DX Recurrence Score =\< 10). II. To compare the outcomes projected at 10 years by Adjuvant (with outcomes projected using classical pathologic information including tumor size, hormone receptor status, and histologic grade) with those made by the Genomic Health Oncotype DX test. Classical pathologic information and outcome results will also be used to create and refine models that would use classical information instead of or in combination with genomic tests. III. To estimate failure rates as a function of recurrence score (RS) separately in the chemotherapy (arms C, D) and no chemotherapy (arms A, B) groups. The purpose of the analysis is to develop more precise estimates of the relationship between recurrence score and chemotherapy treatment effect, if any, at the upper range of the RS 11 - 25 group. IV. To determine the prognostic significance of the Oncotype DX recurrence score and of the individual RS gene groups (proliferation gene group, human epidermal growth factor receptor \[HER\]2 gene group, estrogen receptor \[ER\] gene group, invasion gene group, and other genes). TERTIARY OBJECTIVES: I. To evaluate the effects of chemotherapy and hormonal therapy vs hormonal therapy alone on perceived cognitive impairment, fatigue, fear of recurrence among pre-menopausal patients, endocrine symptoms and sexual dysfunction, and overall health-related quality of life (HRQL). II. To determine whether perceived cognitive impairment, fatigue, fear of recurrence, endocrine symptoms, and overall HRQL are similar for patients receiving chemotherapy plus hormonal therapy in secondary study group 2 as for those in the primary study group (arm D vs C). III. To determine whether perceived cognitive impairment, fatigue, fear of recurrence, endocrine symptoms, and overall HRQL are similar for patients receiving hormonal therapy alone in secondary study group 1 as for those in the primary study group (arms A vs B). IV. To determine whether age will be inversely associated with a fear of recurrence, independent of treatment assignment. V. Among participants receiving hormonal treatment alone on arm A and arm B, to determine whether Oncotype DX Recurrence score will be inversely correlated with fear of recurrence. VI. To create a biospecimen repository including plasma, serum and CellSearch cassettes containing circulating tumor cells (CTC) for evaluating determinants of late relapse, including candidate biomarkers reflecting occult tumor burden (e.g., CTCs and plasma tumor DNA) and host factors (e.g., estrogen, insulin growth factor-\[IGF\] axis, inflammation, etc). VII. To create a biorepository of metastatic tumor samples in patients who have had a late relapse. VIII. To determine body mass index (BMI) and comorbidity burden in patients with operable breast cancer five or more years after diagnosis. IX. To determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence. OUTLINE: This is a partially randomized study. Patients are assigned to 1 of 3 treatment groups. GROUP 1 (SECONDARY STUDY GROUP 1; ONCOTYPE DX RECURRENCE SCORE \[ODRS\] =\< 10): Patients receive standard hormonal therapy (e.g., tamoxifen alone orally (PO), aromatase inhibitor \[e.g., anastrozole, letrozole, or exemestane\] alone PO, or tamoxifen PO followed by aromatase inhibitor PO) at the discretion of the treating physician for 5 or 10 years. GROUP 2 (PRIMARY STUDY GROUP; ODRS 11-25): Patients are randomized to receive either hormonal therapy alone or combination chemotherapy and hormonal therapy. ARM I (EXPERIMENTAL): Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. ARM II (STANDARD): Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician. GROUP 3 (SECONDARY STUDY GROUP 2; ODRS \>= 26): Patients receive combination chemotherapy as in Group 2, Arm II followed by hormonal therapy as in Group 1. Patients in all groups who have had breast-conservation surgery are also treated with radiotherapy. Radiotherapy should begin within 4 weeks of registration for patients receiving hormonal therapy alone or within 8 weeks after completion of chemotherapy. Patients participating in National Surgical Adjuvant Breast and Bowel Project (NSABP) and/or Radiation Therapy Oncology Group (RTOG) partial irradiation trial(s) may receive partial breast radiation. After completion of study treatment, patients are followed up every 3-6 months for 5 years and then annually for 15 years.