• Age 45 - 65

• Postmenopausal female

‣ Postmenopausal is defined as prior removal of the ovaries, or if ovaries intact amenorrhea for 12 months and not on any form of contraception, or amenorrhea for greater than 2 months with serum follicle-stimulating hormone (FSH) in postmenopausal range (\>= 25 IU/L). Women with ovaries and a prior hysterectomy or endometrial ablation \< age 55 must have a FSH within the postmenopausal range. Women may be on vaginal low dose estrogen preparations for vaginal dryness. Women over age 50 with a levonorgestrel intrauterine device in place for 2 or more years are also eligible if FSH is in the postmenopausal range and they are not planning removal for the next 6 months

• Note: FSH will be done at time of screening

• Women with intact ovaries and uterus \< age 55 must have a negative pregnancy test prior to randomization

• Obese (body mass index \[BMI\] \>= 30 kg/m\^2) OR overweight (BMI 25 to \< 30 kg/m\^2) WITH at least two or more of the following elements of metabolic syndrome documented in the past 180 days prior to randomization:

‣ Waist circumference of \>= 89 cm

⁃ Blood pressure over 130/85 mmHg (or current treatment for hypertension)

⁃ Fasting triglyceride (TG) level over 150 mg/dl

⁃ Fasting high-density lipoprotein (HDL) \< 50 mg/dl (or current statin treatment)

⁃ Fasting glucose \> 100 mg/dl

⁃ Note: BMI must be calculated within 28 days of randomization

• Willing to undergo a fasting blood draw and non-fasting RPFNA with fixed and frozen aliquots sent to University of Kansas Medical Center (KUMC)

• At increased risk of breast cancer per at least one of the following:

‣ Personal medical history

• History of atypical hyperplasia or lobular carcinoma in situ (LCIS) found on breast biopsy

∙ History of unilateral ductal carcinoma in situ treated with unilateral mastectomy, lumpectomy, or local excision with or without radiation and this treatment was completed at least 3 months prior to the screening RPFNA

∙ High mammographic density determined by one of the following:

‣ Visual estimate of area of density (VAS) \> 50%,

⁃ Volpara (trademark) \>= 15% dense volume (Volpara d)

⁃ Breast Imaging Reporting and Data System (BIRADS) assessment = extremely dense (BIRADs D)

⁃ Genetic test result

• Germline gene mutation in ATM, BARD1, CDH1, CHEK2, NF1, PTEN, RAD51C, RAD51D, or STK11

∙ Polygenic lifetime risk score \>= 2x average or 25%

⁃ Calculated risk based on standard models

• Five-year Breast Cancer Risk Assessment Tool (BCRAT) (version 2.0) \>= 1.66% (https://dceg.cancer.gov/tools/risk-assessment/bcra)

∙ Ten-year International Breast Cancer Intervention Study risk evaluation tool (IBIS) (version 8) \>= 3% (http://www.ems-trials.org/riskevaluator/)

∙ Ten-year relative risk IBIS (version 8) \>= 2X that for age group

∙ Ten- year Breast Cancer Surveillance Consortium (version 2) \>= 3% (https://tools.bcscscc.org/BC5yearRisk/calculator.htm)

⁃ Family History

• Breast cancer in a first or second degree relative (female or male) with onset under age 50. (First degree relative = parent, sibling, or child. Second degree relative = grandparent, uncle, aunt, nephew, niece, half-sibling, grandchild or first cousin)

∙ Breast cancer in two or more first or second-degree relatives from either the maternal or paternal linage without regard to age

∙ Bilateral breast cancer or breast and ovarian cancer in the same first or second degree relative without regard to age

⁃ Primary source documentation of risk is required and must be submitted to the lead academic organization (LAO) for review along with the eligibility checklist

• Risk factor: Atypical hyperplasia or LCIS; Primary source document: Copy of pathology report or clinical note confirming the diagnosis

∙ Risk factor: Ductal carcinoma in situ (DCIS) and treatment history; Primary source document: Copies of pathology report or clinic notes confirming the diagnosis, treatment plan and treatment end date(s)

∙ Risk factor: Mammographic density; Primary source document: Copy of clinic note or mammogram report

∙ Risk factor: Genetic; Primary source document: Copy of genetic test report

∙ Risk factor: Calculated based on standard models; Primary source document: Copy of the calculation result

• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)

‣ Note: Higher total bilirubin levels (=\< 3 mg/dL) can be allowed if due to known benign liver condition, i.e., Gilbert's syndrome

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 3.0 x institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

• Women must have at least 1 unaffected untreated breast for fine needle aspiration. Women may have had prior unilateral breast radiation or mastectomy for DCIS

• Ability to understand and the willingness to sign a written informed consent document

• Most recent screening mammogram must be performed ≤ 12 months prior to RPFNA and must be reported as BIRAD 1 or 2. If BIRAD 0 then follow-up diagnostic imaging must be BIRAD 1 or 2 or cleared clinically with radiology recommendation of return to annual screening