Molecular Testing and Imaging in Improving Response in Patients With Stage I-III Triple-Negative Breast Cancer Receiving Chemotherapy MDACC Breast Moonshot Initiative

This clinical trial assesses whether a newly designed algorithm which looks at the genomic signature of each patient's tumor to predict their sensitivity to standard of care treatment verses being placed on a personally designed treatment trial can improve the responses in patients with newly diagnosed triple-negative breast cancer (TNBC). Testing the primary tumor biopsy for certain proteins and monitoring the lymphocyte infiltration into the tumors may help doctors determine the sub-type of TNBC, and direct treatments that may work well. It is not yet known whether assigning treatment based on the patient's tumor classification will improve how well the tumor responds.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* The patient can undergo biopsy or surgery of a primary tumor site for suspected or proven invasive breast cancer of clinical stage I to III and are planned to receive neoadjuvant therapy with anthracycline/taxane based regimens (Arm A and Arm B) or chemotherapy/immunotherapy-based regimens (Arm C)
* The patient was proven to have TNBC, defined from standard pathologic assays as negative for ER and PR (\< 10% tumor staining) and negative for HER2 (immunohistochemistry \[IHC\] score \< 3, gene copy number not amplified)
* Patients must have left ventricular ejection fraction (LVEF) \>= 50% by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) within 12 weeks prior to starting adriamycin
* Leukocytes \> 3,000/mcL
* Absolute neutrophil count \> 1,500/mcL
* Platelets \> 100,000/mcL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional upper limit of normal
* Creatinine within 1.5 X the upper limits of normal OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* For Arms A and B, patients must be medically ineligible to receive immunotherapy in combination with anthracycline/taxane-based chemotherapy as part of standard care
* For Arm C, patients must be medically eligible to receive immunotherapy in combination with chemotherapy as part of standard of care

Exclusion Criteria:

* The patient has diagnosis of stage IV disease or is found to have stage IV disease prior to initiation of chemotherapy
* Prior history of invasive cancer within 5 years of study entry or history of metastatic cancer; exceptions include non-metastatic, curatively treated basal and squamous cell carcinoma of the skin
* Prior excisional biopsy of the primary invasive breast cancer
* Patients with hematomas or biopsy site changes that limit response assessment of the primary tumor by diagnostic imaging
* Patients not eligible for chemotherapy with taxane and/or anthracycline based chemotherapy regimens
* Prior therapy with - chemotherapy and/or immunotherapy
* Grade II or higher neuropathy
* Patients with Zubrod performance status of \> 2
* Patients with history of serious cardiac events defined as:

  * Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina or cerebrovascular accident (CVA) within 6 months of protocol registration
  * Patients who have history of PR prolongation (grade 2 or higher) or atrioventricular (AV) block

• DERIVEDSeth S, Yam C, Huo L, Lim B, Rinkenbaugh AL, White JB, Ravenberg EE, Song X, Litton JK, Tripathy D, Valero V, Damodaran S, Arun B, Ueno NT, Lucci A, Thompson AM, Mittendorf EA, Rauch GM, Adrada B, Candelaria RP, Ding Q, Powell RT, Abuhadra NK, Zhang J, Futreal A, Draetta GF, Piwnica-Worms H, Symmans WF, Chang JT, Moulder SL. The ARTEMIS trial identifies immune activation as a key predictor of neoadjuvant chemotherapy response in triple-negative breast cancer. Breast Cancer Res. 2026 May 6;28(1):120. doi: 10.1186/s13058-026-02290-z. PMID 42093035
• DERIVEDWang X, Zhao L, Song X, Wu X, Krishnamurthy S, Semba T, Shao S, Knafl M, Coffer LW 2nd, Alexander A, Vines A, Bopparaju S, Woodward WA, Chu R, Zhang J, Yam C, Loo LWM, Nasrazadani A, Huong LP, Woodman SE, Futreal A; Rare Tumor Initiative Team; Tripathy D, Ueno NT. Genomic and transcriptomic analyses identify distinctive features of triple-negative inflammatory breast cancer. NPJ Precis Oncol. 2024 Nov 18;8(1):265. doi: 10.1038/s41698-024-00729-0. PMID 39558017
• DERIVEDStowers CE, Wu C, Xu Z, Kumar S, Yam C, Son JB, Ma J, Tamir JI, Rauch GM, Yankeelov TE. Combining Biology-based and MRI Data-driven Modeling to Predict Response to Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer. Radiol Artif Intell. 2025 Jan;7(1):e240124. doi: 10.1148/ryai.240124. PMID 39503605
• DERIVEDBasho RK, Zhao L, White JB, Huo L, Bassett RL, Mittendorf EA, Thompson A, Litton JK, Ueno N, Arun B, Lim B, Valero V, Tripathy D, Zhang J, Adrada BE, Santiago L, Ravenberg E, Seth S, Yam C, Moulder SL, Damodaran S. Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes. JCO Precis Oncol. 2024 Mar;8:e2300124. doi: 10.1200/PO.23.00124. PMID 38484209
• DERIVEDChen H, Ding Q, Khazai L, Zhao L, Damodaran S, Litton JK, Rauch GM, Yam C, Chang JT, Seth S, Lim B, Thompson AM, Mittendorf EA, Adrada B, Virani K, White JB, Ravenberg E, Song X, Candelaria R, Arun B, Ueno NT, Santiago L, Saleem S, Abouharb S, Murthy RK, Ibrahim N, Routbort MJ, Sahin A, Valero V, Symmans WF, Tripathy D, Wang WL, Moulder S, Huo L. PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens. Ther Adv Med Oncol. 2023 Aug 2;15:17588359231189422. doi: 10.1177/17588359231189422. eCollection 2023.