Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.

Background: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).

Methods: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX).

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC.

Impact of TP53 mutations in Triple Negative Breast Cancer.

Identifying triple negative breast cancer (TNBC) patients expected to have poor outcomes provides an opportunity to enhance clinical management. We applied an Evolutionary Action Score to functionally characterize TP53 mutations (EAp53) in 96 TNBC patients and observed that EAp53 stratification may identify TP53 mutations associated with worse outcomes. These findings merit further exploration in larger TNBC cohorts and in patients treated with neoadjuvant chemotherapy regimens.

Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers.

Germline mutations in BRCA1 or BRCA2 exist in ~2-7% of breast cancer patients, which has led to the approval of PARP inhibitors in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. As nearly half of the patients treated did not have pCR, better strategies are needed to overcome treatment resistance.

Molecular Characterization and Prospective Evaluation of Pathologic Response and Outcomes with Neoadjuvant Therapy in Metaplastic Triple-Negative Breast Cancer.

Purpose: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.

Experimental Design: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy.

Quantitative Apparent Diffusion Coefficients From Peritumoral Regions as Early Predictors of Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer.

Background: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC.

Purpose: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC.

Mid-treatment Ultrasound Descriptors as Qualitative Imaging Biomarkers of Pathologic Complete Response in Patients with Triple-Negative Breast Cancer.

This study aimed to investigate mid-treatment breast tumor ultrasound characteristics that may predict eventual pathologic complete response (pCR) in triple-negative breast cancer; specifically, we examined associations between pCR and two parameters: tumor response pattern and tumor appearance. Ultrasound was performed at mid-treatment, defined as the completion of four cycles of anthracycline-based chemotherapy and before receiving taxane-based chemotherapy. Consensus imaging review was performed while blinded to pathology results (i.

A model combining pretreatment MRI radiomic features and tumor-infiltrating lymphocytes to predict response to neoadjuvant systemic therapy in triple-negative breast cancer.

Purpose: We aimed to develop a predictive model based on pretreatment MRI radiomic features (MRIRF) and tumor-infiltrating lymphocyte (TIL) levels, an established prognostic marker, to improve the accuracy of predicting pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) patients.

Methods: This Institutional Review Board (IRB) approved retrospective study included a preliminary set of 80 women with biopsy-proven TNBC who underwent NAST, pretreatment dynamic contrast enhanced MRI, and biopsy-based pathologic assessment of TIL. A threshold of ≥ 20% was used to define high TIL.

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2 breast cancer in the adaptively randomized I-SPY2 trial.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.

Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone.

Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer.

Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24 metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24 gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models.

BI-RADS Ultrasound Lexicon Descriptors and Stromal Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

Purpose: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC.

Materials And Methods: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial.

Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer.

Purpose: Increasing tumor-infiltrating lymphocytes (TIL) is associated with higher rates of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). However, the presence of TILs does not consistently predict pCR, therefore, the current study was undertaken to more fully characterize the immune cell response and its association with pCR.

Experimental Design: We obtained pretreatment core-needle biopsies from 105 patients with stage I-III TNBC enrolled in ARTEMIS (NCT02276443) who received NAT from Oct 22, 2015 through July 24, 2018.

Functional Tumor Volume by Fast Dynamic Contrast-Enhanced MRI for Predicting Neoadjuvant Systemic Therapy Response in Triple-Negative Breast Cancer.

Background: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response.

Purpose: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Comparison of three FDA-approved diagnostic immunohistochemistry assays of PD-L1 in triple-negative breast carcinoma.

The Dako 28-8, Dako 22C3, and Ventana SP142 assays are among the approved programmed death ligand 1 (PD-L1) immunohistochemical companion/complementary diagnostics associated with cancer treatment. To address the concordance of these assays in triple-negative breast cancer (TNBC), we examined PD-L1 expression in 98 TNBC tumors and compared the positive rates using the three assays and three scoring methods: immune cell (IC), tumor cell (TC), and combined tumor cell and immune cell (TCIC) (an equivalent to combined positive score, or CPS). The positive rate for PD-L1 expression with a 1% cutoff was highest with 28-8, followed by the 22C3.

Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

Purpose: To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC.

Methods: This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010-2018.

Axillary ultrasound during neoadjuvant systemic therapy in triple-negative breast cancer patients.

Purpose: To investigate the value of performing mid-treatment axillary ultrasound (AUS) in triple-negative breast cancer (TNBC) patients who are undergoing neoadjuvant systemic therapy (NAST) by determining the optimal cutoff number of abnormal nodes associated with residual nodal disease on surgical pathology.

Materials And Methods: This sub-study, an interim analysis of an ongoing single-institution clinical trial enrolling patients with stage I-III TNBC, included 106 patients. Number of abnormal nodes at mid-treatment was assessed and recorded by experienced breast radiologists, who empirically categorized lymph nodes using a binary approach of sonographically-normal versus abnormal.