This phase II trial studies how well anastrozole and letrozole after surgery work in treating patients with stage I-III breast cancer. Drugs, such as anastrozole and letrozole, may stop the growth of tumor cells by decreasing the amount of estrogen made by the body. Giving anastrozole and letrozole after surgery may prevent breast cancer from coming back (recurrence).

PRIMARY OBJECTIVE:

I. To estimate the proportion of women who have adequate estrone (E1) and estradiol (E2) suppression after 8-10 weeks of adjuvant anastrozole 10 mg once daily (ANA10) having had inadequate E1 and E2 suppression after 8-10 weeks of standard dose anastrozole 1 mg once daily (ANA1).

SECONDARY OBJECTIVES:

I. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1.

II. To estimate the proportion of women with elevated E1 and E2 levels after 8-10 weeks of adjuvant ANA1 whose E1 and E2 levels remain elevated after 8-10 weeks of adjuvant ANA10.

III. To examine the toxicity profile of ANA1 over the 8-10 weeks of treatment, ANA10 over the 8-10 weeks of treatment, and letrozole over the 8-10 weeks of treatment.

IV. To examine concentrations of anastrozole at both the ANA1 and ANA10 dose levels.

V. To examine E1 and E2 concentrations, as well as letrozole drug levels, in patients receiving letrozole (following ANA10).

VI. To bank deoxyribonucleic acid (DNA) for examination of single-nucleotide polymorphism (SNP)-set(s) determined in the ongoing Mayo Clinic Breast Cancer Specialized Program of Research Excellence (SPORE) Project 4.

EXPLORATORY OBJECTIVE:

I. To examine association between clinical variables such as age, age at menopause, body mass index (BMI), receipt of chemotherapy, chemotherapy regimen, and dose on E1 and E2 levels after 8-10 weeks of ANA10.

OUTLINE:

Patients receive anastrozole orally (PO) once daily (QD) for 56-70 days (8-10 weeks). Patients with E1 >= 1.3 pg/ml and E2 >= 0.5 pg/ml continue to receive anastrozole PO QD for another 56-70 days (8-10 weeks). Patients then receive letrozole PO QD for 8-10 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

• REGISTRATION-INCLUSION CRITERIA

• Disease characteristics:

  • Histological confirmation of invasive breast carcinoma
  • Stage I-III breast cancer
  • Estrogen receptor (ER) positive disease according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines as ER >= 1% positive nuclear staining

• Completion of all planned cancer treatments prior to registration:

  • Surgical resection of breast and nodal surgery; (NOTE: Reconstructive surgery does not have to be completed)
  • Adjuvant radiation therapy, if needed
  • Neoadjuvant and/or adjuvant chemotherapy, if needed

• Post-menopausal defined as

  • Age >= 60 and amenorrhea > 12 consecutive months OR

  • Previous bilateral oophorectomy OR

  • Age < 60 and amenorrhea > 12 consecutive months and documented follicle stimulating hormone (FSH) level within post-menopausal range according to institutional standard

    • NOTE: Patients who did not meet these criteria at time of diagnosis and received pre-operative (neoadjuvant) or post-operative (adjuvant) chemotherapy will not be allowed to participate

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

• Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)

• Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)

• Platelet count >= 70,000/mm^3 (obtained =< 14 days prior to registration)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to registration)

• Ability to swallow oral medication

• Provide written informed consent

• Willingness to provide mandatory blood specimens for correlative research

• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

• RE-REGISTRATION-INCLUSION CRITERIA

• Confirmation that baseline blood sample was drawn and submitted

• Blood estrogen levels after cycle 1 anastrozole (ANA1) must meet the following criteria:

  • E1 >= 1.3 pg/ml, AND
  • E2 >= 0.5 pg/ml

Exclusion Criteria:

• REGISTRATION-EXCLUSION CRITERIA

• Pre-menopausal women receiving ovarian function suppression (goserelin, leuprolide, etc.)

• Stage IV (metastatic) breast cancer

• HER2 positive breast cancer as defined by

  • HER2 immunohistochemistry (IHC) >= 3+
  • HER2/CEP17 >= 2.0
  • HER2/CEP17 < 2.0 and average HER2 copy number of >= 6.0 signals/cell

• Prior endocrine therapy for this breast cancer. Exceptions:

  • Pre-operative aromatase therapy (anastrozole, letrozole, or exemestane) and last treatment was >= 4 weeks prior to registration OR
  • Pre-operative tamoxifen therapy and last treatment was >= 12 weeks prior to registration

• Currently receiving any of the following cancer-directed therapies:

  • Radiation therapy
  • Systemic therapy such as chemotherapy (standard or investigational)

• Bisphosphonate therapy started < 4 weeks prior to registration

  • NOTE: If patient is currently on bisphosphonate therapy she must be on stable dose for >= 4 weeks prior to registration. Patients not currently taking bisphosphonates will be allowed to start bisphosphonate therapy after completion of anastrozole (1 mg and 10 mg daily [if given]). Information regarding bisphosphonate therapy will be collected

• Current use of systemic or topical exogenous estrogen or progesterone (menopausal hormone replacement therapy [HRT])

• Prior ovarian function suppression (leuprolide, goserelin, etc.)

• Inability to provide informed consent

• History of contralateral ductal carcinoma in situ (DCIS) or invasive breast cancer

  • NOTE: Exception allowed if

    • Patient did not receive adjuvant endocrine therapy OR
    • Patient received adjuvant endocrine therapy but has been off treatment for at least 6 months prior to registration

• Concurrent active malignancy or history of malignancy =< 3 years prior to registration

  • NOTE: Exceptions allowed for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, papillary thyroid cancer, or non-melanoma skin cancer

• Prior prevention therapy with an aromatase inhibitor or a selective estrogen receptor modulator (SERM). Exception: Therapy with a SERM (tamoxifen or raloxifene) is allowed if patient has been off treatment for >= 6 months prior to registration