Capecitabine monotherapy as first-line treatment in advanced HER2-normal breast cancer - a nationwide, retrospective study.

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.

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.

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).

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.

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.