Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.

Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6) to block cell cycle progression have been effective in treating hormone receptor-positive breast cancer, but triple-negative breast cancer (TNBC) remains largely resistant, limiting their clinical applicability. The study reveals that transcription regulator cyclin-dependent kinase7 (CDK7) is a promising target to circumvent TNBC's inherent resistance to CDK4/6 inhibitors. Combining CDK4/6 and CDK7 inhibitors significantly enhances therapeutic effectiveness, leading to a marked decrease in cholesterol biosynthesis within cells.

Clinical outcomes after post-operative radiotherapy for breast cancer patients presenting with ipsilateral supraclavicular metastasis: considerations on the cranial border of irradiation field.

Background: Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients.

Methods: Between July 2016 and January 2022, a total of 268 patients were eligible for analysis.

CXCR6 expression correlates with radiotherapy response and immune context in triple-negative breast cancer-experimental studies.

Background: The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

Background: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes.

Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial.

Importance: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear.

Objective: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases.

Design, Setting, And Participants: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase.

Favorable prognosis of breast cancer brain metastases patients with limited intracranial and extracranial metastatic lesions.

Background: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions.

A retrospective study of adjuvant proton radiotherapy for breast cancer after lumpectomy: a comparison of conventional-dose and hypofractionated dose.

Purpose: This study aimed to compare the adverse reactions of conventional-dose and hypofractionated dose of proton therapy for breast cancer.

Materials And Methods: Breast cancer patients treated with proton radiotherapy in conventional-dose or hypofractionated dose were studied retrospectively.

Result: From January 2017 to December 2019, our center treated 50 patients following lumpectomy with proton radiotherapy.

The Role of Radiotherapy for Patients with Unresectable Locally Advanced Breast Cancer following Neoadjuvant Systemic Therapy.

Background: For locally advanced breast cancer (LABC) patients who remained unresectable after neoadjuvant systemic therapy (NST), radiotherapy (RT) is considered as an approach for tumor downstaging. In this study, we attempted to discuss the value of RT for patients with unresectable or progressive disease in the breast and/or regional nodes following NST.

Methods: Between January 2013 and November 2020, the data for 71 patients with chemo-refractory LABC or de novo bone-only metastasis stage IV BC who received locoregional RT with or without surgical resection were retrospectively analyzed.

Entire Versus Medial Supraclavicular Nodal Irradiation for Patients With High-Risk Node-Positive Breast Cancer.

Purpose: We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves SCL control and survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI).

Methods And Materials: We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from January 2015 to December 2016. High-risk features were defined as clinical or pathologic stage N2-3b disease.

Molecular subtypes predict second breast events of ductal carcinoma in situ after breast-conserving surgery.

Purpose: Currently, the prognostic value of molecular subtypes in ductal carcinoma in situ (DCIS) remains unclear. In this study, we explored whether molecular subtypes could predict second breast events (SBEs) in patients after breast-conserving surgery (BCS).

Methods: From January 2008 to December 2016, 291 DCIS patients treated with BCS were retrospectively analyzed.

Prognostic value of metabolic signature on 18F-FDGuptake in breast cancer patients after radiotherapy.

Radiotherapy (RT) is a major modality of postoperative treatment in breast cancer. The maximal standardized value (SUVmax) is FDG-PET/CT derived parameter that reported to be a valuable prognostic factor in cancer patients. Herein, we aimed to identify a prognostic gene signature associated with glucose uptake for breast cancer patients after RT by leveraging the mRNA expression profiling on public datasets.

Delayed initiation of radiation therapy is associated with inferior outcomes for breast cancer patients with hormone receptor-negative tumors after breast-conserving surgery.

Background: To investigate whether the interval between adjuvant chemotherapy (CT) completion and postoperative radiation therapy initiation (ICR) after breast-conserving surgery (BCS) affects ipsilateral breast tumor recurrence (IBTR) or survival.

Methods: All women who were diagnosed with invasive breast cancer and underwent BCS between 2005 and 2014 were included. In total, 1,472 patients underwent adjuvant CT followed by postoperative radiation therapy (RT) (CT+), whereas 402 patients received postoperative RT alone (CT-).

Characteristics, prognosis, risk factors, and management of recently diagnosed ductal carcinoma in situ with microinvasion.

Background: Ductal carcinoma in situ with microinvasion (DCISM) represents ~1% of all breast cancer cases and is arguably a more aggressive subtype of ductal carcinoma in situ (DCIS). Lacking studies with a large population, the survival outcomes of DCISM are still poorly understood and the treatment recommendations remain controversial. This study aims to investigate the long-term outcome of patients with DCISM, potential risk factors for their prognosis, and the difference of survival between patients treated with breast-conserving surgery plus radiotherapy (BCT + RT) and mastectomy only.

Impact of clinical-pathological factors on locoregional recurrence in mastectomy patients with T1-2N1 breast cancer: who can omit adjuvant radiotherapy?

Purpose: Postmastectomy radiation therapy (PMRT) in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs) is controversial. This study was to identify prognostic factors of locoregional control (LRC) following mastectomy with or without PMRT for patients with T1-2N1 breast cancer and to discuss the selection of patients who might omit PMRT.

Materials And Methods: Between January 2006 and December 2012, the data of 1474 postmastectomy patients staged pT1-2N1 were analyzed.

Symptoms Related to Brachial Plexus Neuropathy After Supraclavicular Irradiation and Boost in Breast Cancer.

Purpose: To evaluate the incidence of symptoms related to brachial plexus neuropathy (BPN) and the dose distribution to the brachial plexus (BP) in patients with breast cancertreated with supraclavicular (SCV) irradiation and boost.

Methods And Materials: In this study, 117 patients with initial ipsilateral supraclavicular lymph node (SLN) metastasis and 39 with recurrent SLN metastasis between 2008 and 2018 in our cancer center were retrospectively analyzed. All patients were treated with 50 Gy of SCV irradiation in 25 fractions and a boost (median dose, 10 Gy; range, 10-16 Gy) to involved nodes in the SCV area.

Outcomes in Patients with pT3N0M0 Breast Cancer with and without Postmastectomy Radiotherapy.

Purpose: The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for patients with pT3N0M0 breast cancer, especially when patients are treated with the updated adjuvant chemotherapy. Our study aimed to compare locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in pT3N0M0 patients with and without postmastectomy radiotherapy.

Patients And Methods: Between October 2000 and 8 September 2016, the database of the Breast Cancer Center of Shanghai yielded 114 patients with node-negative non-metastatic breast cancer larger than 5 cm.

Postoperative radiotherapy improves overall survival in patients with primary squamous cell carcinoma of the breast.

Background: Primary squamous cell carcinoma of the breast (PSCCB) is a rare clinical classification of breast tumors. Little is known about its clinicopathological features, prognosis and potential therapeutic strategies. The purpose of this study is to evaluate the effect of postoperative radiotherapy (PORT) on patients with squamous cell carcinoma (SCC) of the breast.

CDK4/6 inhibitors: a novel strategy for tumor radiosensitization.

Recently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies.

Adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneous integrated boost for early stage breast cancer : Results from a phase II trial.

Purpose: To report early toxicity and 5‑year clinical outcomes of adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB) after breast-conserving surgery for early stage breast cancer patients.

Patients And Methods: In all, 467 patients including 406 invasive breast cancer and 61 ductal carcinoma in situ (DCIS) were enrolled in a single institutional phase II trial. All patients underwent IMRT-SIB treatment to irradiate the whole breast and the tumor bed.

Building radiation-resistant model in triple-negative breast cancer to screen radioresistance-related molecular markers.

Background: To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance.

Methods: We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines.

Biological subtype predicts locoregional recurrence after postmastectomy radiotherapy in Chinese breast cancer patients.

Aim: To investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT).

Methods And Materials: About 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A-like, Luminal B-like, HER2-positive, and triple-negative breast cancer (TNBC).

Internal mammary node irradiation improves 8-year survival in breast cancer patients: results from a retrospective cohort study in real-world setting.

Background: Regional nodal irradiation (RNI) improves disease outcome in breast cancer patients, but the contribution of internal mammary node irradiation (IMNI) in the context of modern systemic treatment is still controversial. The aim of our study is to evaluate the effect of IMNI in patients with modern systemic treatment in real-world setting.

Methods: We retrospectively analyzed patients with primary breast cancer treated with surgery followed by adjuvant chemotherapy and adjuvant chestwall/breast irradiation and RNI from 5/2007-12/2010.

The Impact of Radiotherapy on Reoperation Rates in Patients Undergoing Mastectomy and Breast Reconstruction.

Objective: The aim of this study was to determine the impact of postmastectomy radiotherapy (PMRT) on reoperation rates in women with breast cancer undergoing mastectomy and breast reconstruction.

Methods: Between June 2001 and December 2015, 832 breast cancer patients treated with mastectomy and breast reconstruction with (n = 159) or without (n = 673) PMRT were analyzed retrospectively. Reoperations following breast reconstruction were categorized into the following three types: anticipated, unanticipated, and others.

Internal Mammary Node Irradiation (IMNI) Improves Survival Outcome for Patients With Clinical Stage II-III Breast Cancer After Preoperative Systemic Therapy.

Purpose: The indication for internal mammary node irradiation (IMNI) after preoperative systemic therapy in breast cancer remains vague. This study was designed to evaluate the effect of IMNI in patients with clinical stage II-III breast cancer after preoperative systemic therapy and surgery.

Methods And Materials: Between August 2005 and December 2013, 497 patients with clinical stage II-III breast cancer underwent anthracycline- or taxane-based preoperative systemic therapy, surgery, and postoperative radiation therapy.