Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy.

Purpose: Stromal tumor-infiltrating lymphocytes (sTIL) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in the setting of anthracycline-based chemotherapy. The impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known.

Experimental Design: This is a pooled analysis of two studies where patients with stage I (T>1 cm)-III TNBC received carboplatin (AUC 6) plus docetaxel (75 mg/m2; CbD) NAC.

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer: NeoPACT Phase 2 Clinical Trial.

Importance: Addition of pembrolizumab to anthracycline-based chemotherapy improves pathologic complete response (pCR) and event-free survival (EFS) in triple-negative breast cancer (TNBC). The efficacy of anthracycline-free chemoimmunotherapy in TNBC has not been assessed.

Objective: To assess the efficacy of the anthracycline-free neoadjuvant regimen of carboplatin and docetaxel plus pembrolizumab in TNBC.

Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease. We previously showed that homologous recombination deficiency (HRD) and the DNA damage immune response (DDIR) signature are prognostic in TNBC. We hypothesized that these biomarkers reflect related but not completely interdependent biological processes, that their combined use would be prognostic, and that simultaneous assessment of the immunologic microenvironment and susceptibility to DNA damaging therapies might be able to identify subgroups with distinct therapeutic vulnerabilities.

Individualising radiation therapy decisions in breast cancer patients based on tumour infiltrating lymphocytes and genomic biomarkers.

Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology. A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT.

Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial.

Importance: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.

Objective: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.

Design, Setting, And Participants: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy.

ctDNA and residual cancer burden are prognostic in triple-negative breast cancer patients with residual disease.

Triple-negative breast cancer (TNBC) patients with residual disease (RD) after neoadjuvant systemic therapy (NAST) are at high risk for recurrence. Biomarkers to risk-stratify patients with RD could help individualize adjuvant therapy and inform future adjuvant therapy trials. We aim to investigate the impact of circulating tumor DNA (ctDNA) status and residual cancer burden (RCB) class on outcomes in TNBC patients with RD.

EGFR as a potent CAR T target in triple negative breast cancer brain metastases.

Purpose: There is currently no curative treatment for patients diagnosed with triple-negative breast cancer brain metastases (TNBC-BM). CAR T cells hold potential for curative treatment given they retain the cytolytic activity of a T cell combined with the specificity of an antibody. In this proposal we evaluated the potential of EGFR re-directed CAR T cells as a therapeutic treatment against TNBC cells in vitro and in vivo.

Impact of low versus negative estrogen/progesterone receptor status on clinico-pathologic characteristics and survival outcomes in HER2-negative breast cancer.

Triple-negative breast cancer (TNBC) is classically defined by estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry expression <1% and absence of HER2 amplification/overexpression. HER2-negative breast cancer with low ER/PR expression (1-10%) has a gene expression profile similar to TNBC; however, real-world treatment patterns, chemotherapy response, endocrine therapy benefit, and survival outcomes for the Low-ER group are not well known. 516 patients with stage I-III HER2-negative breast cancer and ER/PR expression ≤10% who were enrolled in a multisite prospective registry between 2011 and 2019 were categorized on the basis of ER/PR expression.

Outcomes After Breast Radiation Therapy in a Diverse Patient Cohort With a Germline BRCA1/2 Mutation.

Purpose: BRCA1/2 pathogenic variant (PV) mutations confer radiation sensitivity preclinically, but there are limited data regarding breast cancer outcomes after radiation therapy (RT) among patients with documented BRCA1/2 PV mutations versus no PV mutations.

Methods And Materials: This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery and RT and underwent BRCA1/2 genetic evaluation at the The University of Texas MD Anderson Cancer Center. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status.

Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing.

Purpose: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing.

Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion.

Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study, we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC vs non-IBC tumors, independently of molecular subtype.

Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer.

Purpose: mutations are common in breast cancer and promote tumor progression and treatment resistance. We conducted a phase I/II trial of alpelisib (α-specific PI3K inhibitor) plus nab-paclitaxel in patients with HER2-negative metastatic breast cancer (MBC).

Patients And Methods: Eligible patients had HER2-negative MBC with any number of prior chemotherapies.

Radiation Sciences Education in Africa: An Assessment of Current Training Practices and Evaluation of a High-Yield Course in Radiation Biology and Radiation Physics.

Purpose: Formal education in the radiation sciences is critical for the safe and effective delivery of radiotherapy. Practices and patterns of radiation sciences education and trainee performance in the radiation sciences are poorly described. This study assesses the current state of radiation sciences education in Africa and evaluates a high-yield, on-site educational program in radiation biology and radiation physics for oncology and radiation therapy trainees in Africa.

Excellent Locoregional Control in Inflammatory Breast Cancer With a Personalized Radiation Therapy Approach.

Purpose: Inflammatory breast cancer (IBC) has been characterized by high locoregional recurrence (LRR) rates even after trimodality therapy. We recently reported excellent locoregional control among patients treated since formal dedication of an IBC-specific clinic and research program in 2006. Institutionally, a standard twice-daily (BID) dose escalation regimen for all patients with IBC was de-escalated in select cases in 2006 after review demonstrated that young age, incomplete response to neoadjuvant therapy, and positive margins identified subsets with maximal benefit from dose escalation.

Prospective Comparison of Toxicity and Cosmetic Outcome After Accelerated Partial Breast Irradiation With Conformal External Beam Radiotherapy or Single-Entry Multilumen Intracavitary Brachytherapy.

Purpose: This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy.

Methods And Materials: A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014.

Long-Term Impact of Regional Nodal Irradiation in Patients With Node-Positive Breast Cancer Treated With Neoadjuvant Systemic Therapy.

Purpose: The impact of regional nodal irradiation (RNI) on locoregional recurrence (LRR) and any disease recurrence (DR) in women with node-positive breast cancer who receive neoadjuvant systemic therapy (NAT) is unknown.

Methods And Materials: The impact of RNI on LRR and DR was estimated with the cumulative incidence method in 1289 women with stage II to III breast cancer with cytologically confirmed axillary metastases who received NAT between 1989 and 2007. Multicovariate Cox regression analysis was performed to examine the effect of RNI after accounting for other predictive and prognostic variables.

Effectiveness of definitive radiotherapy for squamous cell carcinoma of the vulva with gross inguinal lymphadenopathy.

Objective: To evaluate the effectiveness and long-term side effects of definitive groin radiotherapy for vulvar cancer with grossly involved inguinal lymph nodes.

Methods: The records of 407 women with vulvar squamous cell carcinoma treated with radiotherapy at one institution during 1992-2014 were reviewed to identify patients who had radiographic or histologic evidence of grossly involved inguinal lymph nodes. Patients with lymphadenectomy before radiotherapy and patients treated for recurrent disease were excluded.

Outcomes and patterns of relapse after definitive radiation therapy for oligometastatic cervical cancer.

Purpose: Survival rates for women with metastatic cervical cancer are low, with limited management options. Definitive radiation therapy (RT) for oligometastatic disease has led to prolonged survival in other malignancies, but this approach has yet to be systematically studied for cervical cancer.

Methods And Materials: We evaluated 38 patients who received definitive RT to oligometastatic sites of cervical cancer at a single institution from 2002 to 2015.

Lack of Breastfeeding History in Parous Women with Inflammatory Breast Cancer Predicts Poor Disease-Free Survival.

Breastfeeding alters the breast microenvironment, and several lines of evidence suggest the breast microenvironment contributes to the clinical phenotype of inflammatory breast cancer. We investigated breastfeeding history as a modifier of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) in parous women with inflammatory breast cancer. Parous women with inflammatory breast cancer were identified from a prospective registry at The University of Texas MD Anderson Cancer Center.

Improved Locoregional Control in a Contemporary Cohort of Nonmetastatic Inflammatory Breast Cancer Patients Undergoing Surgery.

Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer characterized by rapid progression and early metastatic dissemination. The purpose of this study was to assess contemporary rates of local regional recurrence (LRR) in the era of trimodality therapy for nonmetastatic IBC and identify risk factors leading to local failure.

Methods: A total of 114 patients with nonmetastatic IBC receiving trimodality therapy (neoadjuvant chemotherapy, surgery, and radiation therapy) were identified from a prospectively collected database from 2007 to 2015 and outcomes analyzed.

Patterns of recurrence and survival in neuroendocrine cervical cancer.

Objective: To analyze patterns of recurrence and survival and identify prognostic factors in women with neuroendocrine cervical cancer (NECC).

Methods: We reviewed patients with International Federation of Gynecology and Obstetrics stage I-IVA NECC who were enrolled in the Neuroendocrine Cervical Tumor Registry and treated with curative intent. Event-free survival (EFS) and overall survival (OS) according to disease and treatment characteristics were analyzed using the Kaplan-Meier method.

Post-Mastectomy Radiation Therapy for Invasive Lobular Carcinoma: A Comparative Utilization and Outcomes Study.

Background: To date, there have been no analyses to assess factors that influence post-mastectomy radiation therapy (PMRT) utilization in invasive lobular carcinoma (ILC) or to quantify the benefit of PMRT in ILC as compared with invasive ductal carcinoma (IDC). We compared histology-specific utilization of PMRT by tumor and patient characteristics and estimated the effect of PMRT on overall and breast cancer-specific survival in ILC and IDC patients meeting American College of Radiology (ACR) criteria for PMRT.

Patients And Methods: We used the Surveillance, Epidemiology, and End Results database to identify women diagnosed with ILC or IDC from 2004 to 2009 who underwent mastectomy.

The prognostic value of promoter methylation in early stage triple negative breast cancer.

Introduction: Methylation of the promoter is frequent in triple negative breast cancers (TNBC) and results in a tumor phenotype similar to -mutated tumors. mutation-associated cancers are more sensitive to DNA damaging agents as compared to conventional chemotherapy agents. It is not known if there is an interaction between the presence of promoter methylation (PM) and response to chemotherapy agents in sporadic TNBC.