Rifaximin for the Treatment of Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy in Patients With Stage I-III HER2 Positive Breast Cancer

Inclusion Criteria:

* PRE-REGISTRATION INCLUSION CRITERIA
* Age \>= 18 years
* Histological confirmation of HER2 positive breast cancer stage I-III per American Joint Committee on Cancer (AJCC) staging 8th edition
* Provide written informed consent
* Breast cancer patients who will be receiving pertuzumab-based chemotherapy with either TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) or docetaxel/paclitaxel, trastuzumab, and pertuzumab
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
* Hemoglobin \>= 10.0 g/dL (obtained =\< 30 days prior to pre-registration)
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 30 days prior to pre-registration)
* Platelet count \>= 100 x 10\^9/L (obtained =\< 30 days prior to pre-registration)
* Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) (obtained =\< 30 days prior to pre-registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (obtained =\< 30 days prior to pre-registration)
* Serum or plasma creatinine =\< 1.5 x ULN (obtained =\< 30 days prior to pre-registration)
* Calculated creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 30 days prior to pre-registration)
* Negative serum pregnancy test done =\< 30 days prior to pre-registration, for person of childbearing potential only
* Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* Willingness to provide mandatory stool specimen for correlative research
* Ability to complete questionnaire(s) by themselves or with assistance
* REGISTRATION INCLUSION CRITERIA
* Received pertuzumab based regimens in the adjuvant or neoadjuvant setting
* Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (obtained =\< 14 days prior to registration)
* Platelet count \>= 100 x 10\^9/L (obtained =\< 14 days prior to registration)
* Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) (obtained =\< 14 days prior to registration)
* AST (SGOT)/ALT (SGPT) =\< 2.5 x ULN (obtained =\< 14 days prior to registration)
* Serum or plasma creatinine =\< 1.5 x ULN (obtained =\< 14 days prior to registration)
* Calculated creatinine clearance \>= 45 ml/min using the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)

Exclusion Criteria:

* PRE-REGISTRATION EXCLUSION CRITERIA
* History of myocardial infarction =\< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment

  * EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
* Uncontrolled intercurrent non-cardiac illness including, but not limited to:

  * Ongoing or active infection
  * Psychiatric illness/social situations
  * Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  * Any other conditions that would limit compliance with study requirements
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy

  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm (adjust to protocol if applicable)
* Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown

  * Pregnant women
  * Nursing women
  * Women of childbearing potential who are unwilling to employ adequate contraception
* Current colostomy or ileostomy
* History of inflammatory bowel disease
* History of irritable bowel syndrome
* History of arteriovenous malformations
* History of gastrointestinal bleeds
* Previous surgical resection of the small bowel or colon
* Previous allergy to rifaximin or its derivatives