Search

Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment. Material and Methods: The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5–18.0), and median PFS was 6.0 months (95% CI: 5.3–6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45–70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01). Interpretation: In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies., Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment. MATERIAL AND METHODS: The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01). INTERPRETATION: In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

Background and purpose: We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification. Materials and methods: Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI). Results: 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status. Interpretation: HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity., BACKGROUND AND PURPOSE: We investigated the prognosis of breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2), as previous studies have found varying impacts on survival of HER2-low BC compared with HER2 0 BC (HER2 IHC score of 0). HER2-low is defined as a score of 1+ or 2+ in an immunohistochemical (IHC) assay without HER2 gene amplification. MATERIALS AND METHODS: Patients with HER2 0 or HER2-low BC from the national Danish Breast Cancer Group database were examined by multivariable survival analysis in a retrospective noninterventional investigation. Patients were grouped as either HER2 0 or HER2-low. The primary endpoint was time to recurrence (TR), and the secondary endpoints were overall survival (OS) and distant recurrence-free interval (DRFI). RESULTS: 41,610 patients were included (12,981 with HER2 0 BC and 28,629 with HER2-low BC). HER2-low BC was associated with a lower risk of recurrence (hazard ratio [HR]: 0.92, p = 0.03). Regarding secondary endpoints, HER2-low disease was linked to improved overall OS (HR: 0.94, p = 0.02). No statistically significant effect of HER2-low was found for DRFI, along with no differential effect of HER2-low according to estrogen receptor (ER) status. INTERPRETATION: HER2-low BC was found to show an improved HR for OS and DRFI compared with HER2 0 BC; however, further studies are need to establish whether it represents a separate biological entity.

Background For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. Methods In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. Findings 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 4·3/1000 person-years of foll, Background: For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. Methods: In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. Findings: 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 4·3/1000 person-years of follow-up) and 170

Background: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results. Methods: We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses. Results: A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01–1.08) and shorter survival (HR, 1.13; 95% CI, 1.09–1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17–1.45 and 1.65; 95% CI, 1.39–1.95, respectively. Conclusions: Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. Impact: CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer., BACKGROUND: Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results. METHODS: We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses. RESULTS: A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01-1.08) and shorter survival (HR, 1.13; 95% CI, 1.09-1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17-1.45 and 1.65; 95% CI, 1.39-1.95, respectively. CONCLUSIONS: Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. IMPACT: CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer.

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., 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.

BACKGROUND. Intrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation. METHODS. The 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. RESULTS. In 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. CONCLUSION. Our 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., BACKGROUND. Intrinsic molecular subtypes define distinct biological breast cancers and can be used to further improve diagnosis and risk allocation. METHODS. The 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. RESULTS. In 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. CONCLUSION. Our 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.

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, 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%); an

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.

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 o