Locoregional Lymph Node Metastasis from Clinically Occult Breast Cancer: Prognostic Significance of Mastectomy.

Materials And Methods: This study included patients registered in the national Danish Breast Cancer Group (DBCG) database between 2001 and 2015, with locoregional LNM as well as a bilateral negative mammography, ultrasonography, and physical examination of the breasts. Overall survival (OS) and invasive disease-free survival (IDFS) were compared by treatment groups, ALND + RT (axillary lymph node dissection and radiotherapy) or ALND + MAST ± RT (axillary lymph node dissection, mastectomy with or without radiotherapy).

Results: In total, 56 patients were included in the study, of which 37 were treated by ALND + RT, 16 by ALND + MAST ± RT, and the remaining three patients receiving different treatments.

Overall survival after CDK4/6 inhibitor dose reduction in women with metastatic breast cancer.

Background: Breast cancer is the most common cancer in women, and the first-line treatment for patients with hormone-receptor positive/HER2-negative metastatic breast cancer is CDK4/6 inhibitor plus endocrine therapy. Understanding the impact of CDK4/6 inhibitor dose reduction, which occurs in about half of the patients, is important.

Methods: This real-world cohort study is based on electronic health records from Capital Region of Denmark.

Adjuvant Docetaxel and Cyclophosphamide With or Without Epirubicin for Early Breast Cancer: Final Analysis of the Randomized DBCG 07-READ Trial.

The primary analysis of the DBCG 07-READ trial reported in 2017 provided evidence of no overall benefit from adjuvant anthracyclines in patients with early normal breast cancer in disease-free survival (DFS), distant disease-free survival (DDFS), or overall survival (OS). We performed a protocol-scheduled analysis of DDFS, DFS, and OS on the basis of 10-year follow-up. Full details on incident heart failure (HF) and second cancers were presented.

Evaluating the Prognostic Role of the PAM50 Signature and Selected Immune-Related Signatures for Recurrence in Patients With T1abN0 Breast Cancer.

Background: De-escalation of adjuvant treatment in patients with T1abN0 breast cancer is discussed internationally. Identification of new prognostic factors in these patients may assist this de-escalation. The PAM50 signature and tumor inflammation signature (TIS), Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) signatures are possible prognostic factors for recurrence.

Incidence and survival of primary metastatic breast cancer in Denmark; implication of breast cancer screening, classification, and staging practice.

Background: Primary metastatic breast cancer (pMBC) accounts for 5-10% of annual breast cancers with a median survival of 3-4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented.

Molecular subtyping improves breast cancer diagnosis in the Copenhagen Breast Cancer Genomics Study.

BACKGROUNDIntrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation.METHODSThe Copenhagen Breast Cancer Genomics Study (CBCGS) prospectively included women diagnosed with breast cancer at Rigshospitalet from 2014 to 2021. Eligible patients were females with a primary invasive breast cancer (T1c, if N0M0; otherwise, any T, any N, or any M stage) and no prior malignancy.

Development and Methodological Validation of a Modified Staging System for de Novo Metastatic Breast Cancer.

Importance: Validation of a new method for prognostication of de novo metastatic breast cancer (dnMBC) to better reflect the heterogenecity of the disease.

Objective: To perform external methodological validation of the Plichta staging system, a novel prognostic system for de novo metastatic breast cancer (dnMBC).

Design, Setting, And Participants: This retrospective cohort study used a multicenter, nationwide, population-based Danish Breast Cancer Group database to validate the new method.

Adjuvant treatment with trastuzumab of patients with HER2-positive, T1a-bN0M0 breast tumors: A systematic review and meta-analysis.

The benefit of adjuvant trastuzumab treatment in patients with HER2-positive breast tumors ≤ 10 mm without lymph node involvement (T1abN0) is insufficiently investigated. The aim of this systematic review and meta-analysis was to examine if adjuvant trastuzumab improves the prognosis in these patients. Databases were searched to identify interventional and observational studies evaluating the effect of trastuzumab on breast cancer specific survival (BCSS), disease free survival (DFS), distant recurrence free survival (DRFS), overall survival (OS) or recurrence free survival (RFS).

Adjuvant chemotherapy in patients with ER-negative/HER2-negative, T1abN0 breast cancer: a nationwide study.

Purpose: The purpose of this study was to examine the effect of chemotherapy on invasive disease-free survival (iDFS) and overall survival (OS) in a nationwide cohort of patients with estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative, T1abN0 breast cancer.

Methods: Patients with ER-negative/HER2-negative, T1abN0 breast cancer registered in the Danish Breast Cancer Group database between 2007 and 2016 were identified. The effect of adjuvant chemotherapy on iDFS and OS was analyzed with Cox proportional hazards analysis.

Benefit of adjuvant chemotherapy and trastuzumab in patients with HER2-positive, node-negative breast tumors ≤ 10 mm: a nationwide study.

Purpose: The purpose of this study was to evaluate the effect of chemotherapy and trastuzumab on invasive disease-free survival (iDFS) and overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2) positive, T1abN0 breast cancer.

Methods: In the Danish Breast Cancer Group database, patients with HER2-positive, T1abN0 tumors diagnosed between 2007 and 2016 were identified. Cox proportional hazards analysis was performed to analyze the association between adjuvant chemotherapy and trastuzumab and iDFS and OS.

[Targeted treatment of HER2-positive metastatic breast cancer improves prognosis significantly].

Breast cancer is the most common type of cancer among women in Denmark. In 15% of the patients with metastatic breast cancer (mBC) an overexpression of the HER2 protein on the tumour cells, amplification of the HER2-gene or both are present. HER2-positive mBC is associated with poor disease prognosis.

Induction of PIK3CA alterations during neoadjuvant letrozole may improve outcome in postmenopausal breast cancer patients.

Purpose: Estrogen receptor positive (ER+) breast cancer constitutes almost 85% of all breast cancer patients and are a genetically highly heterogenic group. Data on the association of somatic alterations to outcome and prognosis are however sparse. In this neoadjuvant endocrine phase II trial including postmenopausal breast cancer patients with ER+, HER2 normal breast cancer, we investigated the rate of pathogenic mutations before and after treatment as well as the association with treatment response and survival.

Synchronous bilateral breast cancer: a nationwide study on histopathology and etiology.

Purpose: The aim of the present study was to describe histopathologic characteristics of synchronous bilateral breast cancer (SBBC), and by comparing SBBC to unilateral breast cancer (UBC), identify possible etiological mechanisms of SBBC.

Methods: Patients with primary SBBC (diagnosed within 4 months) and UBC diagnosed in Denmark between 1999 and 2015 were included. Detailed data on histopathology were retrieved from the Danish Breast Cancer Group database and the Danish Pathology Register.

Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: analysis from a nationwide phase II DBCG trial.

Background: The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.

Patients' experience of communication and handling of symptomatic adverse events in breast cancer patients receiving adjuvant chemotherapy.

Background: The study is based on a national cluster randomized trial investigating the effect of electronic patient-reported outcomes (ePRO) on treatment outcomes in breast cancer patients receiving adjuvant chemotherapy. All 13 oncology departments (11 clusters) treating breast cancer patients in Denmark were randomized to use electronic patient-reported outcomes with real-time clinician feedback (ePRO arm) to track symptoms or usual care for eliciting symptoms using a short paper tracking list (usual care arm). The impact of ePRO on clinical outcomes were examined, which is reported elsewhere.

Prediction of fulvestrant efficacy in patients with advanced breast cancer: retrospective-prospective evaluation of the predictive potential of a multigene expression assay.

Background: Fulvestrant is a selective oestrogen receptor (ER) degrader used as monotherapy and combination therapy for ER positive HER2 negative advanced breast cancer (ABC) in postmenopausal women. The drug response predictor (DRP), is a mathematical algorithm based on the expression of multiple genes in the tumour. The fulvestrant DRP algorithm has previously shown effect in BC.

Breast cancer mortality in synchronous bilateral breast cancer patients.

Background: Evidence suggests that patients with synchronous bilateral breast cancer (SBBC), diagnosed within 4 months, have an inferior prognosis compared to unilateral breast cancer (UBC) patients. Using data from nationwide Danish clinical databases, this cohort study investigated whether the inferior prognosis could be explained by SBBC patients having a more aggressive disease, or whether the prognosis could be explained by the fact that they have two simultaneous cancers.

Methods: Patients were diagnosed from 1999-2015.

Predicting efficacy of epirubicin by a multigene assay in advanced breast cancer within a Danish Breast Cancer Cooperative Group (DBCG) cohort: a retrospective-prospective blinded study.

Purpose: Anthracyclines remain a cornerstone in the treatment of primary and advanced breast cancer (BC). This study has evaluated the predictive value of a multigene mRNA-based drug response predictor (DRP) in the treatment of advanced BC with epirubicin. The DRP is a mathematical method combining in vitro sensitivity and gene expression with clinical genetic information from > 3000 clinical tumor samples.

Correlation between circulating cell-free PIK3CA tumor DNA levels and treatment response in patients with PIK3CA-mutated metastatic breast cancer.

Liquid biopsies focusing on the analysis of cell-free circulating tumor DNA (ctDNA) may have important clinical implications for personalized medicine, including early detection of cancer, therapeutic guidance, and monitoring of recurrence. Mutations in the oncogene, PIK3CA, are frequently observed in breast cancer and have been suggested as a predictive biomarker for PI3K-selective inhibitor treatment. In this study, we analyzed the presence of PIK3CA mutations in formalin-fixed, paraffin-embedded, metastatic tissue and corresponding ctDNA from serum of patients with advanced breast cancer using a highly sensitive, optimized droplet digital PCR (ddPCR) assay.

PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer.

Purpose The PAM50-based Prosigna risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR). The value of Prosigna for predicting DR was examined in a comprehensive nationwide Danish cohort consisting of postmenopausal women with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were treated with endocrine therapy for 5 years.

Identification of metastasis driver genes by massive parallel sequencing of successive steps of breast cancer progression.

Cancer results from alterations at essential genomic sites and is characterized by uncontrolled cell proliferation, invasion and metastasis. Identification of driver genes of metastatic progression is essential, as metastases, not primary tumors, are fatal. To gain insight into the mutational concordance between different steps of malignant progression we performed exome sequencing and validation with targeted deep sequencing of successive steps of malignant progression from pre-invasive stages to asynchronous distant metastases in six breast cancer patients.

Forty years of landmark trials undertaken by the Danish Breast Cancer Cooperative Group (DBCG) nationwide or in international collaboration.

Background: Over the past 40 years the Danish Breast Cancer Cooperative Group (DBCG) has made significant contributions to improve outcome and to make treatment of patients with early breast cancer more tolerable through nationwide and international trials evaluating loco-regional and systemic treatments. These trials have been instrumental to establish standards for the treatment of early breast cancer.

Methods: The DBCG 82 trials had a global impact by documenting that the significant gain in loco-regional recurrence from postmastectomy radiation added to systemic therapy was associated with a reduction in distant recurrence and mortality in high-risk pre- and postmenopausal patients.

Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG).

Introduction: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design.

Material And Methods: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive surgery.

Mortality and recurrence rates among systemically untreated high risk breast cancer patients included in the DBCG 77 trials.

Background: Following loco-regional treatment for early breast cancer accurate prognostication is essential for communicating benefits of systemic treatment. The aim of this study was to determine time to recurrence and long-term mortality rates in high risk patients according to patient characteristics and subtypes as assigned by immunohistochemistry panels.

Patients And Methods: In November 1977 through January 1983, 2862 patients with tumors larger than 5 cm or positive axillary nodes were included in the DBCG 77 trials.

Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial.

Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non-anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m) and cyclophosphamide (600 mg/m) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m) and cyclophosphamide (600 mg/m) followed by three cycles of docetaxel (100 mg/m; EC-D).