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. MATERIAL AND METHOD: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. RESULTS: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000-2004 to 1,323 patients in 2015-2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography-computed tomography) or CT (computed tomography) with a bone evaluation in 2000-2004 and 65% in 2015-2020. Overall survival (OS) improved from 23 months in 2000-2004 to 33 months in 2015-2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. INTERPRETATION: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

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. All patients underwent molecular profiling with the CIT256 and PAM50 molecular profile.RESULTSIn the study period, 2,816 patients were included in the CBCGS. Molecular subtyping showed an increase in nonluminal (molecular-apocrine, luminal C, and Basal-like) as compared with luminal (luminal A, luminal B, and Normal-like) subtypes with increasing stage from I to IV. Across all stages, we found a significant difference in survival among subtypes; 91% of patients with LumA were alive at 5 years compared with 91% for LumB, 84% for LumC, 82% for mApo, and 80% for Basal-like. We identified 442 tumors (16%) that were discordant in subtype between CIT256 and IHC. Discordant subtype proved to be a risk factor of death among patients with IHC luminal breast cancer (hazard ratio [HR], 2.08; 95% CI, 1.51-2.86) in a multivariable Cox regression analysis. Discordance occurred more often among patients with N3, stage IV, or grade III disease.CONCLUSIONOur findings indicate that molecular subtypes are a predominant classification for survival. Assessment is particularly crucial for patients with IHC luminal breast cancer with known high-risk factors, since they are at an increased risk of harboring an aggressive molecular subtype.

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. Participants were patients with dnMBC diagnosed between 2010 and 2019. Data were analyzed from April to June 2023. Main outcomes and measures: A recursive partitioning analysis (RPA) was performed, as demonstrated by Plichta and colleagues, to group patients with similar overall survival (OS) based on clinical factors. The main outcome was to group patients into 4 prognostic groups based on 3-year OS as stage IVa, greater than 70%; stage IVb, 50% to 70%; stage IVc, 25% to less than 50%; or stage IVd, less than 25%. Bootstrapping was applied for 1000 iterations, with final stage assignments based on the most commonly occurring assignment. Results: A total of 1859 women were included with a median (IQR) age of 69 (57-77) years. With a median potential follow-up of 89.9 (95% CI, 86.4-95.1) months and a median OS of 31.7 (95% CI, 29.5-34.1) months, the RPA stratified patients into 10 groups, with organ sites, estrogen receptor status, and human epidermal growth factor receptor 2 status as the key clinical factors. Three-year survival rates ranged from 62% (95% CI, 56%-69%) to 8% (95% CI, 3%-21%), which were further combined into 3 stage groups: IVb, 59.4% (95% CI, 56.2%-62.8%); IVc, 39.4% (95% CI, 36.2%-43.0%); and IVd, 15.4% (95% CI, 11.2%-21.3%) (P < .001). Following bootstrapping, an IVa group emerged, resulting in 4 stage groups with separate 3-year OS rates identified as IVa, 75.8% (95% CI, 67.8%-84.7%); IVb, 58.8% (95% CI, 55.5%-62.3%); IVc, 39.2% (95% CI, 35.8%-43.0%); and IVd, 14.4% (95% CI, 10.8%-19.4%) (P < .001). Conclusions and relevance: These findings provide external and independent validation of the methods applied in the novel Plichta staging system for dnMBC. This could guide future revisions of the current American Joint Committee on Cancer staging guidelines and may be incorporated as a stratification factor in clinical trials.

Machine learning applied in patient-reported outcome research-exploring symptoms in adjuvant treatment of breast cancer.

BACKGROUND: Patient-reported outcome (PRO) data may help us better understand the life of breast cancer patients. We have previously collected PRO data in a national Danish breast cancer study in patients undergoing adjuvant chemotherapy. The aim of the present post-hoc explorative study is to apply Machine Learning (ML) algorithms using permutation importance to explore how specific PRO symptoms influence nonadherence to six cycles of planned adjuvant chemotherapy in breast cancer patients. METHODS: We here investigate ePRO-data from the 347 patients. The ePRO presented 42 PROCTCAE questions on 25 symptoms. Patients completed the ePRO before each cycle of chemotherapy. Number of patients with completion of the scheduled six cycles of chemotherapy were registered. Two ML models were applied. One aimed at discovering the individual relative importance of the different questions in the dataset while the second aimed at discovering the relationships between the questions. Permutation importance was used. RESULTS: Out of 347 patients 238 patients remained in the final dataset, 15 patients dropped out. Two symptoms: aching joints and numbness/tingling, were the most important for dropout in the final dataset, each with an importance value of about 0.04. Model's average ROC-AUC-score being 0.706. In the second model a low performance score made the results very unreliable. CONCLUSION: In conclusion, this explorative data analysis using ML methodologies in an ePRO dataset from a population of women with breast cancer treated with adjuvant chemotherapy unravels that the symptoms aching joints and numbness/tingling could be important for drop out of planned adjuvant chemotherapy.

High inter-laboratory variability in the assessment of HER2-low breast cancer: a national registry study on 50,714 Danish patients.

BACKGROUND: Considering the recent advancements in the treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2), we aimed to examine inter-laboratory variability in the assessment of HER2-low breast cancer across all Danish pathology departments. METHODS: From the Danish Breast Cancer Group, we obtained data on all women diagnosed with primary invasive breast cancer in 2007-2019 who were subsequently assigned for curatively intended treatment. RESULTS: Of 50,714 patients, HER2 score and status were recorded for 48,382, among whom 59.2% belonged to the HER2-low group (score 1+ or 2+ without gene amplification), 26.8% had a HER2 score of 0, and 14.0% were HER2 positive. The proportion of HER2-low cases ranged from 46.3 to 71.8% among pathology departments (P < 0.0001) and from 49.3 to 65.6% over the years (P < 0.0001). In comparison, HER2 positivity rates ranged from 11.8 to 17.2% among departments (P < 0.0001) and from 12.6 to 15.7% over the years (P = 0.005). In the eight departments with the highest number of patients, variability in HER2-low cases increased from 2011 to 2019, although the same immunohistochemical assay was used. By multivariable logistic regression, the examining department was significantly related to both HER2 score 0 and HER2 positivity (P < 0.0001) but showed greater dispersion in odds ratios in the former case (range 0.25-1.41 vs. 0.84-1.27). CONCLUSIONS: Our data showed high inter-laboratory variability in the assessment of HER2-low breast cancer. The findings cast doubt on whether the current test method for HER2 is robust and reliable enough to select HER2-low patients for HER2-targeted treatment in daily clinical practice.

Evaluation of tumor-infiltrating lymphocytes, PD-L1, and PIK3CA mutations and association with prognosis in HER2-positive early stage breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have predictive and prognostic potential in HER2-positive breast cancer (HER2+ BC). Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein, with important roles in the tumor microenvironment, possibly in both tumor and immune cells (ICs), providing rationale for targeting with immune-checkpoint therapy. PIK3CA mutations are oncogenic, activating mutations, which are also of relevance in breast cancer. Herein, we investigate the frequency of TILs, PD-L1 and PIK3CA mutations, and whether these factors influence outcome, in early HER2+ BC. MATERIALS AND METHODS: Stromal TILs (sTILs) and PD-L1 expressions were assessed using full tumor-sections and TMA, respectively, from 236 patients with HER2+ BC. TILs were assessed, according to a standardized method, as continuous measurement and according to three predefined categories: low (0-10%), intermediate (11-59%), and high (60-100%). PD-L1 immunohistochemistry (Ventana SP263) was evaluated and positivity defined as ≥1% expression in tumor and ICs. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing. RESULTS: Fourteen percent of patients had high sTILs and 25% had a PIK3CA mutation. PD-L1 expression was more frequent in ICs (68%) than tumor cells (24%). Patients with low sTILs had a significantly worse overall survival (multivariate: HR 2.80; 95% CI 1.36-5.78; p = .02). DISCUSSION: Patients with low sTILs had a significantly poorer survival, despite adequate treatment with adjuvant therapy.

Real-World Survival and Treatment Regimens Across First- to Third-Line Treatment for Advanced Triple-Negative Breast Cancer.

Background: Metastatic triple-negative breast cancer (mTNBC) is an aggressive subtype of breast cancer with poor survival. Currently, the literature lacks comprehensive real-world evidence on locally recurrent and mTNBC patients. To validate the optimal treatment for patients with mTNBC, real-world evidence in combination with data from clinical trials must be evaluated as complementary. Objectives: The objective of the study is to examine outcomes and treatment patterns of patients with advanced triple-negative breast cancer (TNBC) utilizing real-world data of patients from all oncology sites across Denmark. Design: This is a retrospective, non-interventional, multi-site, population-based observational study conducted across all oncology departments in Denmark. Methods: We included all women diagnosed with metastatic or locally recurrent TNBC from January 1, 2017, to December 31, 2019, using the national Danish Breast Cancer Group database. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in the first to third treatment line. Results: The study included 243 women diagnosed with metastatic or recurrent TNBC. The median OS (mOS) was 11.6 months after the first line of treatment, 6.5 months after the second line, and 6.5 months after the third line. De novo mTNBC was associated with shorter OS (mOS: 8.3 vs 14.2 months), and those with a relapse within 18 months of primary diagnosis had shorter OS than those with a relapse after 18 months (mOS: 10.0 vs 18.2). In the first line, taxane was the preferred choice of treatment for patients with de novo mTNBC, whereas capecitabine was preferred for patients with recurrent TNBC. Conclusions: This real-world, nationwide study demonstrated poor OS among patients with metastatic or recurrent TNBC, with a mOS of 11.6 months (95% CI, 9.9-17.3). Patients who presented with de novo mTNBC or who had a relapse of their breast cancer within 18 months of primary diagnosis had shorter OS. Registration: The study was registered and approved by the Danish Capital Regions research overview (P-2021-605).

Atezolizumab and nab-paclitaxel for advanced breast cancer in Danish real-world patients.

INTRODUCTION: The Danish Medicines Council recommends that patients with estrogen receptor and human epidermal growth factor receptor 2-negative, programmed death-ligand 1 (PD-L1)-positive advanced breast cancer receive atezolizumab in combination with nab-paclitaxel. The approval was largely based on results from Impassion130 that showed a beneficial progression-free survival (PFS) and overall survival (OS) in PD-L1-positive patients who received atezolizumab and nab-paclitaxel. METHODS: We conducted a retrospective, population-based study that included patients who received atezolizumab for advanced breast cancer from October 2019 to September 2022. The primary endpoints were PFS and OS. RESULTS: This study included 74 advanced breast cancer patients. Their median age was 54.5 years, and 21 (28.4%) of the patients had de novo advanced disease. Most patients received first-line treatment with atezolizumab (83.8%). The median PFS was 6.0 months (95% confidence interval (CI): 4.7-8.4 months) and the median OS was 14.3 months (95% CI: 9.9-22.2 months). A total of 48 patients received atezolizumab and nab-paclitaxel in accordance with guidelines from the Danish Medicines Council. CONCLUSIONS: This real-world study expectedly showed numerically lower survival outcomes than the phase III trial Impassion130, but met the standards of efficacy set by real-world studies in other countries. A need exists for increased attention to the criteria for receiving atezolizumab. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Oncological Committee of the DBCG, the Research Overview of the Capital (P-2022-828) and the Centre for Health of the Capital Region (R-22060674).

Real-world survival of Danish patients with HER2-positive metastatic breast cancer.

BACKGROUND: The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. MATERIAL AND METHODS: Patients with HER2-positive mBC, diagnosed between 01.01.2014-31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. RESULTS: 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2-48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2-NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1-14.8), 6.6 (95% Cl, 5.8-7.6) and 5.8 (95% Cl, 4.9-6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49-0.98), p = 0.047 and 2.69 (95% CI, 1.45-5.00), p = 0.002, respectively. CONCLUSION: We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases.

A retrospective, non-interventional study of breast cancer patients diagnosed with ER+/HER2 negative, locally advanced or metastatic breast cancer treated with palbociclib in Denmark.

BACKGROUND: The recommended first-line treatment for advanced, ER+/HER2 negative breast cancer is a CDK 4/6 inhibitor in combination with an endocrine backbone. This study investigated the use of palbociclib, as first- or second-line therapy for advanced breast cancer patients in a real-world setting. MATERIAL AND METHODS: This retrospective, population-based study included all Danish, advanced breast cancer patients with ER+/HER2 negative disease who initiated first- or second-line treatment with palbociclib from January 1st, 2017, until December 31st, 2020. The primary outcomes were PFS and OS. RESULTS: The study included 1054 advanced breast cancer patients with a mean age of 66.8 years. Median OS was 51.7 months (95% CI, 44.9-54.6) for all patients in the first-line setting (n = 728) and median PFS was 24.3 months (95% CI, 21.7-27.8). Patients treated in second line (n = 326) had a median OS of 32.5 months (95% CI, 29.9-35.9) and a median PFS of 13.6 months (95% CI, 11.5-15.7). In first-line setting, the PFS and OS were significantly different for endocrine sensitive patients treated with AI (aromatase inhibitor) (n = 423) vs. fulvestrant (n = 158) as endocrine backbone to palbociclib (median PFS AI 31.3 months vs fulvestrant 19.9 months, p = 0.002 and median OS AI 56.9 months vs. fulvestrant 43.6 months, p = 0.001). In endocrine resistant patients (n = 145), no statistically significant difference in PFS was shown (median PFS AI 21.5 months vs. fulvestrant 12.0 months, p = 0.09), whereas OS was significantly different (median OS AI 43.5 months vs. fulvestrant 28.8 months, p = 0.02). CONCLUSION: In this real-world study, treatment with palbociclib combination therapy met the standards of efficacy set by the phase III trials, PALOMA-2 and PALOMA-3, and the standards set by real-world studies in other countries. The study showed significantly different outcomes in terms of PFS and OS in endocrine sensitive patients comparing AI vs. fulvestrant as endocrine backbone to palbociclib as first-line therapy.

Identifying recurrent breast cancer patients in national health registries using machine learning.

BACKGROUND: More than 4500 women are diagnosed with breast cancer each year in Denmark, however, despite adequate treatment 10-30% of patients will experience a recurrence. The Danish Breast Cancer Group (DBCG) stores information on breast cancer recurrence but to improve data completeness automated identification of patients with recurrence is needed. METHODS: We included patient data from the DBCG, the National Pathology Database, and the National Patient Registry for patients with an invasive breast cancer diagnosis after 1999. In total, relevant features of 79,483 patients with a definitive surgery were extracted. A machine learning (ML) model was trained, using a simplistic encoding scheme of features, on a development sample covering 5333 patients with known recurrence and three times as many non-recurrent women. The model was validated in a validation sample consisting of 1006 patients with unknown recurrence status. RESULTS: The ML model identified patients with recurrence with AUC-ROC of 0.93 (95% CI: 0.93-0.94) in the development, and an AUC-ROC of 0.86 (95% CI: 0.83-0.88) in the validation sample. CONCLUSION: An off-the-shelf ML model, trained using the simplistic encoding scheme, could identify recurrence patients across multiple national registries. This approach might potentially enable researchers and clinicians to better and faster identify patients with recurrence and reduce manual patient data interpretation.

A nationwide observational study in heavily pretreated metastatic HER2-positive breast cancer patients.

BACKGROUND: Current guidelines in HER2-positive metastatic breast cancer (mBC) recommend the combination of trastuzumab and a chemotherapeutic agent for 3rd line or later treatments. This study aims to describe the treatment of HER2-positive mBC in 3rd line or later after previous treatment with T-DM1 for mBC in a real-world setting. MATERIAL AND METHODS: This observational population-based study included all women diagnosed with HER2-positive mBC in Denmark, previously treated with T-DM1 in the metastatic setting. Patients were included on the date of progression leading to initiation of 3rd line treatment if the patient had received T-DM1 in 1st or 2nd line. If the patient received T-DM1 in 3rd line or later the inclusion was based on the date of progression on T-DM1. The primary end points were overall survival (OS) and progression-free survival (PFS). RESULTS: The study included 272 women with a mean age of 59 (27-86) and a median of 3 (2-11) treatment lines prior to inclusion. At index, all patients had received T-DM1 and 167 (62%) patients had received pertuzumab in the metastatic setting. During follow-up 183 patients received chemotherapy. Of these patients, 120 received chemotherapy combined with trastuzumab, 50 received chemotherapy combined with other HER2-targeted therapy, and 13 received chemotherapy as monotherapy. The remaining 89 patients received either HER2-targeted monotherapy (41), endocrine therapy (31), experimental treatment (10), or no treatment (7). Median PFS was 5.5 months (95% CI, 4.8-6.5) and median OS was 18.5 months (95% CI, 16.2-21.3). CONCLUSION: In this real-world study, we found that patients were treated with a wide variety of anti-cancer agents with modest efficacy. However, patients in this study did not have access to newer therapies like tucatinib and T-DXd.

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). Twelve studies examining the effect of trastuzumab and nine control studies without trastuzumab were identified (n = 6927). Median follow-up was 36-123 months. Significantly improved DFS (Hazard Ratio (HR) 0.14, p < 0.0001) and OS (HR 0.17, p = 0.011) were found for patients receiving trastuzumab and chemotherapy compared to no trastuzumab/chemotherapy based on four and two studies. The prognosis was good even for patients without trastuzumab treatment: 5-year DFS 88.3% and 5-year OS 95.9%.

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. RESULTS: In total, 296 patients were included in the statistical analyses. Of these, 235 (79.4%) received chemotherapy and 61 patients (20.6%) did not. Patients treated with chemotherapy were significantly younger, had a significantly higher proportion of grade 3 tumors, T1b tumors, and tumors of ductal subtype. With 7.7 years of median follow-up, treatment with chemotherapy was associated with a significant improvement in OS in the adjusted analysis, Hazard Ratio 0.35 (95% Confidence Interval (0.15-0.81), p = 0.02), chemotherapy vs. no chemotherapy. In the unadjusted analyses, patients with both T1a and T1b tumors had significantly improved OS with chemotherapy. At 5 years, OS was 100% vs. 94.4% and 93.8% vs. 81.3% for patients with T1a and T1b tumors, respectively, chemotherapy vs. no chemotherapy. With 4.9 years of median follow-up, iDFS was not significantly improved with chemotherapy. CONCLUSION: Patients with ER-negative/HER2-negative, T1abN0 breast cancer had significantly improved OS when treated with chemotherapy. This improvement was significant in patients with both T1a and T1b tumors, respectively. The effect was, however, limited in patients with T1a tumors.

Interventions supporting cancer patients in making decisions regarding participation in clinical trials - a systematic review.

OBJECTIVES: Existing research on the perspectives of patients with cancer and health care professionals indicates that patient decision making on cancer clinical trial participation is a complex process and may be poorly understood, possibly compromising their decision to participate. This systematic review investigates interventions that support patients in their decision-making processes regarding whether to participate or not and assesses the qualities of the interventions, measures used and related outcomes. METHODS: Six databases were systematically searched and only studies evaluating interventions that support the decision making of adult patients offered to enter a cancer clinical trial were included. Ten articles met the criteria and were analysed using a narrative synthesis approach. RESULTS: The research focus of the included studies reflected the multifactorial nature of what constitutes support for patient decision making in terms of entering a cancer clinical trial. However, most interventions were based on the hypothesis that more information leads to support in decision making, and did not take other factors, such as the relationship to the clinical staff or relatives, the patients' strong hope for therapeutic benefit or other existential needs into account. The interventions were primarily based on a specific tool, executed once, which seems to imply that decisions need only to be supported once and not at several time points throughout the decision process, and did not assess the importance of a patient's family- or social relations. Moreover, few interventions focused on the patients' counselling experience or assessed patient preferences in relation to decision making. CONCLUSIONS: The findings demonstrate a lack of research on interventions to support patients' decision making that takes other factors, apart from improving knowledge of trials, into account. Limited evidence exists on the effectiveness of decision support interventions to improve the experience of support in adult patients with cancer. Interventions that take patient preferences in relation to decision making and the social context of decision processes into account need to be developed and assessed.

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. RESULTS: Of 605 patients included in the analyses, 465 patients received chemotherapy and trastuzumab and 140 patients did not. Chemotherapy and trastuzumab did not improve iDFS or OS significantly in adjusted analyses. 5-year iDFS was 92.3% vs. 89.9%, Hazard ratio (HR) 1.01 (p = 0.98), and 5-year OS was 97.4% vs. 94.3%, HR 0.60 (p = 0.15), chemotherapy and trastuzumab vs. no chemotherapy/trastuzumab. In unadjusted analyses, significant treatment benefit on OS was found in patients with T1b tumors. The largest absolute treatment benefits were found in patients with T1b tumors and estrogen receptor (ER) negative tumors, respectively, whereas treatment effects in patients with T1a tumors and ER-positive tumors, respectively, were limited. CONCLUSION: Adjuvant chemotherapy and trastuzumab did not improve OS or iDFS significantly in patients with HER2-positive, T1abN0 breast cancers in adjusted analyses. In unadjusted analyses, significant OS benefit was found in patients with T1b tumors. The largest absolute benefit was observed in patients with T1b tumors and ER-negative tumors, respectively, whereas the effect was limited in patients with T1a tumors and ER-positive tumors, respectively.

Inter-observer agreement of tumor infiltrating lymphocytes in primary HER2-positive breast cancer and correlation between tissue microarray and full tumor-sections.

Tumor infiltrating lymphocytes (TILs) have predictive and prognostic potential in HER2-positive breast cancer (HER2 + BC). Due to tumor heterogeneity, guidelines recommend evaluation on full tumor-sections over biopsies, but aren't clear regarding tissue microarrays (TMAs). Herein, we investigate the inter-observer agreement of TILs assessment in HER2 + BC on full-sections and TMAs using a standardized method. Two pathologists assessed TILs using HE full-sections and TMAs from 244 patients with HER2 + BC. TILs were assessed in 10% intervals; values <10% evaluated as 0%, 1% or 5%. Levels of agreement were evaluated using intraclass-coefficient (ICC), Kappa statistics and concordance analysis. For inter-observer agreement for full-sections, ICC was 0.93 (95% CI 0.89-0.95) and Kappa was 0.75, corresponding to acceptable and moderate agreement respectively. For TMAs, ICC was 0.73 (95% CI: 0.62-0.81) and Kappa 0.33, corresponding to unacceptable agreement. For association in matched TMA and full-sections, ICC was 0.64 (95% CI 0.55-0.71) and Lin's concordance correlation coefficient was 0.63 (95% CI 0.55-0.71), corresponding to unacceptable agreement. There is acceptable inter-observer agreement of TILs assessment on full-sections but not TMAs and discrepancy between full-sections and TMAs. TMA preparation must include consideration for representation of both entire tumor area and tumor-microenvironment to correctly define prognostic and predictive values of potential immuno-related biomarkers.

First-Line Treatment of HER2-Positive Metastatic Breast Cancer With Dual Blockade Including Biosimilar Trastuzumab (SB3): Population-Based Real-World Data From the DBCG.

Purpose: Dual blockade with trastuzumab and pertuzumab in combination with chemotherapy is the recommended first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). The purpose of this retrospective study is to examine the clinical outcomes of the trastuzumab biosimilar SB3 in first-line dual blockade treatment using real-world data of patients with HER-positive mBC. Methods: In Denmark, all women with breast cancer are registered in the database of the Danish Breast Cancer Group (DBCG). From this prospective observational registry, we extracted information on primary diagnosis and treatment of all women with HER2-positive mBC who received first-line treatment with SB3 and pertuzumab from September 1, 2018, to February 29, 2020. Retrospectively collected data from the DBCG database included information concerning treatment start, end, and reason for discontinuation. The primary endpoints for the study were overall survival (OS) and progression-free survival (PFS). Results: The study included 117 women who received first-line treatment with SB3 and pertuzumab for their HER2-positive mBC. The study population had a mean age of 60 years. A total of 71 patients (61%) had recurrent disease and 46 patients (39%) presented with de novo mBC. The median follow-up was 11.1 and 15.4 months for PFS and OS, respectively. At 12 months, OS was 84% (95% confidence interval [CI], 78-91), whereas the median OS was not reached. The median PFS was 12.7 months (95% CI, 11.1-16.2). Median time on treatment was 8.7 months (95% CI, 7.6-11.4); 36 patients (31%) were still on treatment at end of study. Conclusions: This retrospective real-world, nationwide study demonstrated comparable median PFS to the historical data of using reference trastuzumab and pertuzumab as first-line dual blockade.

[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. The discovery of HER2 led to the development of HER2-targeting monoclonal antibodies significantly improving survival for patients with HER2-positive mBC as summarised in this review. The future brings even more HER2-targeting drugs, which further can contribute to the palliative treatment of HER2-postive mBC patients.

Clinical effects of assessing electronic patient-reported outcomes monitoring symptomatic toxicities during breast cancer therapy: a nationwide and population-based study.

The involvement of cancer patients in symptom reporting talks into our cultural narrative of empowerment and participation in decisions in health of both patients and professionals. Electronic patient-reported outcome (ePRO) is a tool applied for use in such interaction. Based on limited evidence and few empirical studies, health systems are rapidly implementing this instrument in managing patients in active treatment and in follow-up. In a cluster randomized trial of all Danish oncology departments treating breast cancer with adjuvant chemotherapy, we applied ePRO in 347 patients consecutively recruited. Our primary outcome, which was at least one treatment adjustment, was not significantly influenced using ePRO, 34% in the ePRO arm and 41% in the usual care arm received at least one treatment adjustment, p = 0.095. Number of hospitalizations and events of febrile neutropenia were not influenced by the intervention. We believe that one of the main reasons for this finding could be the application of PRO in a well-regulated treatment setting within a public health care system where the most impacting symptomatic toxicities are already taken care off.Trial registration: Clinicaltrials.gov identifier: NCT02996201, registered 19 Dec 2016, retrospectively registered.