An estrogen receptor signaling transcriptional program linked to immune evasion in human hormone receptor-positive breast cancer.

Unlabelled: T cells are generally sparse in hormone receptor-positive (HR+) breast cancer, potentially due to limited antigen presentation, but the driving mechanisms of low T cell abundance remains unclear. Therefore, we defined and investigated programs ('gene modules'), related to estrogen receptor signaling (ERS) and immune signaling using bulk and single-cell transcriptome and multiplexed immunofluorescence of breast cancer tissues from multiple clinical sources and human cell lines. The ERS gene module, dominantly expressed in cancer cells, was negatively associated with immune-related gene modules TNFα/NF-κB signaling and type-I interferon (IFN-I) response, which were expressed in distinct stromal and immune cell types, but also, in part, expressed and preserved as a cancer cell-intrinsic mechanisms.

Risk of Surgical Overtreatment in cN1 Breast Cancer Patients who Become ypN0 After Neoadjuvant Chemotherapy: SLNB Versus TAD.

Background: Two surgical approaches have emerged for axillary staging in cN1 breast cancer patients after neoadjuvant chemotherapy (NAC): sentinel lymph node biopsy (SLNB) and targeted axillary dissection (TAD). Direct comparisons of technical and oncological outcomes with SLNB versus TAD are lacking.

Methods: We routinely performed SLNB from 2017 to 2018 for cN1 breast cancer patients who converted to cN0 after NAC, then adopted TAD from 2019 to 2022.

Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy.

Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also been documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). However, one size does not fit all and predicting which patients will benefit from NACIT remains challenging.

Financial Difficulty Over Time in Young Adults With Breast Cancer.

Importance: Young adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown.

Objectives: To identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty.

ASO Visual Abstract: Real-World Implications of the SOUND Trial.

Nodal disease burden and oncologic outcomes of 312 real-world patients with HR+HER2-breast cancer meeting SOUND eligibility criteria were similar to the SLNB arm of the SOUND trial, supporting careful implementation of omission of SLNB in this population ( https://doi.org/ https://doi.org/10.

Cell Populations in Human Breast Cancers are Molecularly and Biologically Distinct with Age.

Aging is associated with increased breast cancer risk and outcomes are worse for the oldest and youngest patients, regardless of subtype. It is not known how cells in the breast tumor microenvironment are impacted by age and how they might contribute to age-related disease pathology. Here, we discover age-associated differences in cell states and interactions in human estrogen receptor-positive (ER+) and triple-negative breast cancers (TNBC) using new computational analyses of existing single-cell gene expression data.

Quality control for single-cell analysis of high-plex tissue profiles using CyLinter.

Tumors are complex assemblies of cellular and acellular structures patterned on spatial scales from microns to centimeters. Study of these assemblies has advanced dramatically with the introduction of high-plex spatial profiling. Image-based profiling methods reveal the intensities and spatial distributions of 20-100 proteins at subcellular resolution in 10-10 cells per specimen.

Regional Variation in Deescalated Therapy in Older Adults With Early-Stage Breast Cancer.

Importance: Although trial data support the omission of axillary surgery and radiation therapy (RT) in women aged 70 years or older with T1N0 hormone receptor-positive (HR+) breast cancer, potential overtreatment in older adults with frailty persists.

Objective: To determine how much geospatial variation in locoregional therapy may be attributed to region vs patient factors.

Design, Setting, And Participants: This retrospective cross-sectional study included women aged 70 years or older who were diagnosed with HR+/ERBB2-negative (ERBB2-) breast cancer from January 1, 2013, to December 31, 2017.

Concordance of PD-L1 Expression in Metastatic Triple-negative Breast Cancer Between the 22C3 and E1L3N Antibodies Using Combined Positive Scoring.

For patients with metastatic triple-negative breast cancer (TNBC), treatment with pembrolizumab is dependent on the accurate determination of programmed death ligand 1 (PD-L1) expression using immunohistochemistry (IHC). This study evaluated the interobserver concordance in assessing PD-L1 expression on TNBC samples using the commercial 22C3 IHC assay and an in-house assay based on the E1L3N antibody. Concordance between the 22C3 and the E1L3N IHC assays was evaluated on TNBC samples read by a commercial laboratory and a Brigham and Women's Hospital breast pathologist (BWH reader).

Heterogeneity of Residual Disease After Neoadjuvant Systemic Therapy in Breast Cancer: A Review.

Importance: Over the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants.

A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.

Purpose: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.

Generative artificial intelligence as a source of breast cancer information for patients: Proceed with caution.

Background: This study evaluated the accuracy, clinical concordance, and readability of the chatbot interface generative pretrained transformer (ChatGPT) 3.5 as a source of breast cancer information for patients.

Methods: Twenty questions that patients are likely to ask ChatGPT were identified by breast cancer advocates.

PRECISE: Preoperative Radiation Therapy to Elicit Critical Immune Stimulating Effects-A Phase 2 Clinical Trial.

Purpose: Radiation therapy is an underinvestigated tool for priming the immune system in intact human breast cancers. We sought here to investigate if a preoperative radiation therapy boost delivered was associated with a significant change in tumor-infiltrating lymphocytes (TILs) in the tumor in estrogen receptor positive, HER2Neu nonamplified breast cancers.

Methods And Materials: A total of 20 patients were enrolled in a phase 2 clinical trial and received either 7.

Integrative Multiomic Profiling of Triple-Negative Breast Cancer for Identifying Suitable Therapies.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous disease that carries the poorest prognosis of all breast cancers. Although novel TNBC therapies in development are frequently targeted toward tumors carrying a specific genomic, transcriptomic, or protein biomarker, it is poorly understood how these biomarkers are correlated.

Experimental Design: To better understand the molecular features of TNBC and their correlation with one another, we performed multimodal profiling on a cohort of 95 TNBC.

Patient-Reported Outcomes 10 Years After Breast-Conserving Surgery for Early-Stage Breast Cancer.

Background: Patient-reported outcomes (PROs) are a critical component of value-based care. Limited data exist describing long-term PROs in patients undergoing breast-conserving surgery (BCS).

Patients And Methods: Patients undergoing surgery for stage 0-III breast cancer at our institution from 2002 to 2012 who agreed to be contacted were invited to participate in a cross-sectional PRO study.

Potential Overtreatment of DCIS in Patients with Limited Life Expectancy.

Introduction: As the benefits of intensive locoregional therapy for ductal carcinoma in situ (DCIS) are realized over time in older adults, life expectancy may help to guide treatment decisions. We examined whether life expectancy was associated with extent of locoregional therapy in this population.

Patients And Methods: Women ≥ 70 years old with < 5 cm of DCIS diagnosed 2010-2015 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset and categorized by a life expectancy ≤ 5 or > 5 years, defined by a validated claims-based measure.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1.

The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT PREDICT Study.

Background: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit.

Arm morbidity and financial difficulty in breast cancer survivors.

Purpose: Long-term upper extremity symptoms after breast cancer treatment may impact patient-reported financial difficulty. In this cross-sectional investigation, we hypothesized that severity of arm symptoms would be associated with greater financial difficulty.

Methods: Stage 0-III breast cancer patients treated at our institution from 2002 to 2012 were recruited for a 2018 survey study appraising disease-specific patient-centered outcomes using EORTC-QLQ-BR23 and EORTC-QLQ-C30 questionnaires.