PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

Purpose: To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer.

Materials And Methods: A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC).

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

Purpose: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction.

MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA). Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation.

INDIVIDUAL ARTICLE: USCOM Algorithm for the Prevention and Management of Cutaneous Immunotherapy-Related Adverse Events.

Background: In 2023, nearly 2 million patients will be diagnosed with cancer in the United States and at least 40% will be eligible for treatment with an immune checkpoint inhibitor (ICI). Cutaneous immune related adverse events (cirAEs) from ICIs are common and include pruritus as well as maculopapular, eczematous, bullous, lichenoid, and psoriasiform reactions. All clinicians interfacing with cancer patients must expedite proper evaluation and diagnosis, treatment, and/or consultation that supports the need for evidence-directed guidelines.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries.

Materials And Methods: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies.

Radiation Therapy for Low-Risk Breast Cancer: Whole, Partial, or None?

Journal Journal of Clinical Oncology.The following case represents a relatively common clinical scenario of a postmenopausal female patient who presents with low-risk, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative, early-stage, left-sided breast cancer to discuss the role of postoperative radiation (RT) following wide local excision (WLE) and sentinel node biopsy. The spectrum of choices, ranging from omission of RT, accelerated partial breast irradiation (PBI), whole-breast radiation therapy, and the nuances of various dose/fractionation regimens for each option, are discussed in the context of the Danish Breast Cancer Study Group (DBCSG) PBI trial published in this issue, with additional review of other key trials that inform these treatment recommendations.

Radiation Modality (Proton/Photon), Timing, and Complication Rates in Patients With Breast Cancer Receiving 2-Stages Expander/Implant Reconstruction.

Purpose: Our purpose is to explore the effect of postmastectomy radiation therapy (PMRT) modality and timing on complication rates in breast cancer patients receiving immediate 2-stages expander/implant.

Methods And Materials: We reviewed the charts of 661 patients who underwent immediate 2-stages expander/implant with/without PMRT at our institution from 2000 to 2019. Patients were divided into 3 cohorts: no radiation, PMRT to expanders (RTE), and PMRT to implants after expander exchange (RTI).

Immunotherapy Combined with Radiation Therapy in Breast Cancer: A Rapidly Evolving Landscape.

Immune checkpoint inhibitors (ICI) can have significant anticancer activity, and are approved for many different cancer types, including breast cancer. In breast cancer, programmed cell death 1 (PD-1) inhibitors in combination with chemotherapy have demonstrated significant clinical benefit in early-stage and metastatic settings; however, these combinations can have significant side effects, and there are still many breast cancer patients who do not respond to these approaches. Novel combinations with immunotherapy are needed to improve responses.

Risk of Developing Breast Reconstruction Complications: A Machine-Learning Nomogram for Individualized Risk Estimation with and without Postmastectomy Radiation Therapy.

Background: The purpose of this study was to create a nomogram using machine learning models predicting risk of breast reconstruction complications with or without postmastectomy radiation therapy.

Methods: Between 1997 and 2017, 1617 breast cancer patients undergoing mastectomy and breast reconstruction were analyzed. Those with autologous, tissue expander/implant, and single-stage direct-to-implant reconstruction were included.

Current advances in immune checkpoint inhibitor combinations with radiation therapy or cryotherapy for breast cancer.

Purpose: Immune checkpoint inhibition (ICI) has demonstrated clinically significant efficacy when combined with chemotherapy in triple negative breast cancer (TNBC). Although many patients derived benefit, others do not respond to immunotherapy, therefore relying upon innovative combinations to enhance response. Local therapies such as radiation therapy (RT) and cryotherapy are immunogenic and potentially optimize responses to immunotherapy.

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT.

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage.

Radiotherapy to Enhance Chimeric Antigen Receptor T-Cell Therapeutic Efficacy in Solid Tumors: A Narrative Review.

Importance: Immunotherapy has emerged as a new pillar of cancer therapy over the past decade. Adoptive immunotherapy in particular has become a major area of research interest, with advances seen in the development of T-cell engineering. As a result, chimeric antigen receptor (CAR) T-cell therapy has become a new and highly effective treatment option, especially for patients with refractory or resistant blood cell cancers.

ATM Variants in Breast Cancer: Implications for Breast Radiation Therapy Treatment Recommendations.

Purpose: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population.

Methods: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations.

The use of moderately hypofractionated post-operative radiation therapy for breast cancer in clinical practice: A critical review.

Post-operative radiation therapy (RT) reduces loco-regional recurrence rates and mortality in most patients with non-metastatic breast cancer. The aim of this critical review is to provide an overview of the applicability of moderately hypofractionated RT for breast cancer patients, focusing on factors influencing clinical decision-making. An international group of radiation oncologists agreed to assess, integrate, and interpret the existing evidence into a practical report to guide clinicians in their daily management of breast cancer patients.

A pilot study of N-ammonia cardiac PET imaging to assess subacute cardiotoxicity following adjuvant intensity-modulated radiotherapy for locally advanced breast cancer.

Objective: (1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre-/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose.

Methods: Ten left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT.

Quantifying the Impact of Axillary Surgery and Nodal Irradiation on Breast Cancer-Related Lymphedema and Local Tumor Control: Long-Term Results From a Prospective Screening Trial.

Purpose: To independently evaluate the impact of axillary surgery type and regional lymph node radiation (RLNR) on breast cancer-related lymphedema (BCRL) rates in patients with breast cancer.

Patients And Methods: From 2005 to 2018, 1,815 patients with invasive breast cancer were enrolled in a lymphedema screening trial. Patients were divided into the following 4 groups according to axillary surgery approach: sentinel lymph node biopsy (SLNB) alone, SLNB+RLNR, axillary lymph node dissection (ALND) alone, and ALND+RLNR.

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites.

A P53-Independent DNA Damage Response Suppresses Oncogenic Proliferation and Genome Instability.

The Mre11-Rad50-Nbs1 complex is a DNA double-strand break sensor that mediates a tumor-suppressive DNA damage response (DDR) in cells undergoing oncogenic stress, yet the mechanisms underlying this effect are poorly understood. Using a genetically inducible primary mammary epithelial cell model, we demonstrate that Mre11 suppresses proliferation and DNA damage induced by diverse oncogenic drivers through a p53-independent mechanism. Breast tumorigenesis models engineered to express a hypomorphic Mre11 allele exhibit increased levels of oncogene-induced DNA damage, R-loop accumulation, and chromosomal instability with a characteristic copy number loss phenotype.

A phase 2 clinical trial assessing the efficacy and safety of pembrolizumab and radiotherapy in patients with metastatic triple-negative breast cancer.

Background: The current study was conducted to evaluate the efficacy and safety of pembrolizumab-mediated programmed cell death protein 1 inhibition plus radiotherapy (RT) in patients with metastatic triple-negative breast cancer who were unselected for programmed death-ligand 1 expression.

Methods: The current study was a single-arm, Simon 2-stage, phase 2 clinical trial that enrolled a total of 17 patients with a median age of 52 years (range, 37-73 years). An RT dose of 3000 centigrays (cGy) was delivered in 5 daily fractions.