Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer

Inclusion Criteria

• •Males or females age \>= 18 years. Note: Because no dosing or adverse event data are currently available on the use of berzosertib in combination with radiation therapy in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• •Patient with non-metastatic, histologically confirmed primary estrogen receptor (ER) =\< 10%, progesterone receptor (PR) =\< 10%, and HER2-negative breast cancer (triple negative breast cancer \[TNBC\]) either using the baseline biopsy specimen or the post-neoadjuvant chemotherapy (NAC) residual surgical specimen and RCB2 or RCB3, as defined by Symmans et al., 2007, and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has non-metastatic, histologically confirmed primary ER \> 10% and/or PR \> 10%, HER2-negative breast cancer with RCB3 and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has locoregionally recurrent TNBC or ER \>10% and/or PR \>10%, HER2-negative breast cancer.
• •* Note: Results from any Clinical Laboratory Improvement Act (CLIA)-certified lab are acceptable for the purpose of determining study eligibility.
• •* Note: For patients with primary breast cancer, there is no minimum number of neoadjuvant cycles required provided the patient received an anthracycline or taxane preoperatively. Patients with locoregionally recurrent breast cancer are not required to have received preoperative chemotherapy
• •Patient has undergone total mastectomy or wide local excision with axillary staging, and the margins of the resected wide local excision or mastectomy specimens are free of invasive tumor and ductal carcinoma in situ (DCIS) or patient has undergone axillary surgery for regionally recurrent breast cancer. Unresected axillary level III, internal mammary, and supraclavicular nodal disease is permitted.
• •* Note: For patients who have undergone mastectomy, immediate reconstruction is allowed
• •Patients must have completed their final breast surgery, including re-excision of margins for invasive cancer and DCIS, within 90 but not fewer than 21 days prior to registration unless patient received postoperative chemotherapy in which case patients must have completed their adjuvant chemotherapy within 90 days but not fewer than 28 days prior to registration
• •The patient must have recovered from surgery with the incision completely healed and no signs of infection prior to registration
• •Patients must be proceeding with breast/chest wall and regional nodal irradiation including internal mammary node treatment. For patients with bilateral breast cancer, RT must be indicated and administered only to one side
• •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• •Willing to provide tissue and blood samples for correlative research
• •Leukocytes \>= institutional lower limit of normal (LLN)
• •Absolute neutrophil count \>= institutional LLN
• •Platelets \>= institutional LLN
• •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
• •Creatinine =\< 1.1 mg/dL OR
• •Glomerular filtration rate (GFR) \>= 45 mL/min/1.73 m\^2 for patients with creatinine levels above 1.1 mg/dL
• •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
• •Negative urine or serum pregnancy test for individuals of childbearing potential. Note: The effects of berzosertib on the developing human fetus are unknown. For this reason and because DNA-damage repair inhibitors as well as radiation used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 6 months after completion of berzosertib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of berzosertib administration
• •Ability to understand and the willingness to sign a written informed consent document