PURPOSE We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. METHODS We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growt...

Human Epidermal Growth Factor Receptor 2-positive (HER2(+)) breast cancer (BC) is a highly aggressive disease commonly treated with chemotherapy and anti-HER2 drugs, including trastuzumab. There is currently no way to predict which HER2(+) BC patients will benefit from these treatments. Previous prognostic signatures for HER2(+) BC were developed irrespective of the subtype or the hierarchical ...

BACKGROUND HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance o...

The HER2 oncoprotein has emerged as an essential biomarker in the treatment of breast cancer patients. Once the primary breast cancer is removed, there is an increasing need to detect breast cancer recurrence as early as possible with the hope that earlier intervention with new anti-HER2 therapies will improve quality of life and increase overall survival. Numerous publications have shown that ...

HER2 is overexpressed in about 20% of breast cancers and contributes to poor prognosis. Unfortunately, a large fraction of patients have primary or acquired resistance to the HER2-targeted therapy trastuzumab, thus a multi-drug combination is utilized in the clinic, putting significant burden on patients. We systematically identified an optimal HER2 siRNA from 76 potential sequences and demonst...

UNLABELLED Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven of these mutations are activating muta...

SYD985 is a HER2-targeting antibody-drug conjugate (ADC) based on trastuzumab and vc-seco-DUBA, a cleavable linker-duocarmycin payload. To evaluate the therapeutic potential of this new ADC, mechanistic in vitro studies and in vivo patient-derived xenograft (PDX) studies were conducted to compare SYD985 head-to-head with T-DM1 (Kadcyla), another trastuzumab-based ADC. SYD985 and T-DM1 had simil...

There is an urgent need to refine the prognostic taxonomy of HER2+ breast carcinomas and develop easy-to-use, clinic-based prediction algorithms to distinguish between good- and poor- responders to trastuzumab-based therapy. Building on earlier studies suggesting that HER2+ tumors enriched with molecular and morpho-immunohistochemical features classically ascribed to basal-like tumors are highl...

The function of human epidermal growth factor receptor 2 (HER2) in the chemosensitivity of ovarian carcinoma has not been fully investigated, therefore, the present study aimed to analyze the potential role of HER2 in ovarian carcinoma chemosensitivity in further detail. SKOV3 cells were transfected with lentiviral-mediated HER2-small hairpin RNA (shRNA) molecules to establish the stable expres...

BACKGROUND The efficacy and tolerability of the epidermal growth factor receptor/human epidermal growth factor receptor type 2 (HER2) tyrosine kinase inhibitor lapatinib in refractory metastatic breast cancer were assessed. PATIENTS AND METHODS In a phase II, open-label study, patients with previously treated HER2-positive (n = 140) or HER2-negative (n = 89) metastatic breast cancer received ...