NIS Study Determining Prevalence of HER2-low in Metastatic Breast Cancer Patients

Study Overview
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Brief Summary
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This noninterventional, multicenter,retrospective study has been proposed to estimate the prevalence, clinicopathological characteristics,treatment patterns and clinical outcomes of human epidermal growth factor receptor 2 -(HER2)low locally-advanced or metastatic breast cancer(mBC) by accurate rescoring of archived IHC-stained formalin-fixed paraffin-embedded (FFPE) slides for HER2 in patients previously identified as HER2-negative from emerging markets of international regions (non-US and non-European region) with largely unknown prevalence estimates of HER2 low mBCs. Patients with a confirmed diagnosis of HER2-negative, locally-advanced or mBC regardless of Hormone receptor (HR)status between 01 January 2019 and 31 December 2022 who progressed on any systematic anticancer therapy (eg, ET, chemotherapy, CDK4/6 inhibitor, targeted therapies other than anti-HER2, or immunotherapy) in advanced disease with availability of atleast 12 months of follow-up data (from the index date) in the medical records at the participating site, unless patient died within the first 12 months of diagnosis of locally-advanced or mBC will be enrolled in the study. The HR positive patients will be considered eligible for the study if they have received ET as adjuvant therapy in the early BC setting and progressed within 24 months. This scenario will be considered as progression on systematic treatment in the advanced or metastatic setting.

Detailed Description
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Multicenter, noninterventional, retrospective study, aimed to determine the prevalence of HER2-low and HER2>0<1+ by rescoring of archived IHC-stained FFPE slides for HER2 in patients previously identified as having HER2-negative locally-advanced or mBC who progressed on any systemic anticancer therapy.The study will also describe the baseline sociodemographic and clinicopathological characteristics, treatment patterns, clinical outcomes and concordance between historical IHC status and rescored IHC status of archived IHC-stained FFPE slides. The study will not have any study-specific patient visits, procedures, or a longitudinal follow-up. All available data will be extracted from patients' medical records. The study will consist of 2 components: rescoring of archived IHC-stained FFPE slides and secondary data collection from patients' medical records. Human epidermal growth factor receptor 2 IHC historical scores, HER2 rescoring results of archived IHC-stained FFPE slides by qualified laboratory (local and/or independent central laboratory), other biomarker testing results based on historical testing and/or testing of archived tissue samples when available. The data on different types of treatment received by the patients and sociodemographics and clinicopathological characteristics will be extracted from patients' medical records from the date of diagnosis of HER2-negative BC up to the date of data extraction. The patients identified for the current study will be a convenience sample of all patients in the relevant electronic health record/electronic medical record databases and biobanks who meet the inclusion and exclusion criteria; no a priori power analysis will be conducted. The study aims to capture approximately minimal 150 to 200 HER2-negative mBC patients per participating country/cluster, in order to generate data on 2100 to 2700 patients overall, with the aim to identify approximately 1050 HER2-low patients (at least 600 patients in Asia cohort and 450 patients in Latin America [LATAM] cohort) for analysis, subject to revision based on preliminary data analysis. Clinical outcomes will be assessed as per the HER2 subsets identified after rescoring (HER2 low-IHC1+ or IHC2+/ISH-, HER2 IHC>0<1+, HER2 null, and HER2 zero-HER2 IHC>0<1+ and HER2 null). The study will be conducted in 8 Asian countries including Hong Kong, India, Indonesia, Malaysia, Philippines, Thailand, Singapore, and Vietnam and 6 Latin American (LATAM) countries including Argentina, Brazil, Chile, Dominican Republic, Mexico, and Panamá. Regions and countries may be added based on feasibility assessment as per AstraZeneca's standard operating procedures. A total of approximately 2100 to 2700 patients with a confirmed diagnosis of HER2-negative, locally-advanced or mBC regardless of HR status between 01 January 2019 and 31 December 2022 with the availability of medical records of at least 12 months of follow-up data (from the index date), and deemed eligible as per the study eligibility criteria will be enrolled in the study at approximately 28-58 study sites. The study protocol and informed consent form (ICF) will be approved by local Institutional Review Boards (IRBs)/(Institutional) Ethics Committees (IECs) before the commencement of recruitment.

Official Title
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Multicentre NIS Retrospective Study to Know the Prevalence of HER2- Low,Clinical Characteristics,Treatment Patterns,Associated Outcome in Patient With HER2-negative in Metastatic Breast Cancer Who Progressed on Systemic Anticancer Therapy

Conditions
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HER2-negative

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:1. Men or women, ≥18 years of age 2. Provision of informed consent by the patient or next of kin/legal representative (for deceased patients at study entry, unless a waiver was granted) according to local regulations 3. Must have a histological or cytological confirmed previous diagnosis as HER2-negative (IHC zero, 1+, 2+/ISH-) locally-advanced or mBC between 01 January 2019 and 31 December 2022, regardless of HR status 4. Must have progressed on any systemic anticancer therapy (eg, ET, chemotherapy, CDK4/6 inhibitor, targeted therapies other than anti-HER2, or immunotherapy) in the metastatic setting with the availability of at least 12 months of follow-up data (from the index date) in the medical records at the participating site, unless patient died within the first 12 months of diagnosis a) The HR positive patients will be considered eligible for the study if they have received ET as adjuvant therapy in the early BC setting and progressed within 24 months, this scenario will be considered as progression on systematic treatment in the advanced or metastatic setting 5. Must have historical IHC-stained FFPE tissue from locally-advanced or mBC slides for HER2 in an acceptable quality to allow for accurate rescoring of HER2 expression - Exclusion Criteria:1. Have a history of other malignancies, other than basal cell carcinoma of the skin and squamous cell carcinoma of the skin until 3 years prior to diagnosis of locally-advanced or mBC 2. Patients with historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with IHC 1+ or IHC 2+/ISH- HER2 expression. | 1. Proportion of patients with IHC 1+ or IHC 2+/ISH- HER2 expression among previously identified HER2-negative locally-advanced or mBC patients based on rescoring of archived IHC-stained FFPE slides. | 6 months from the Last subject In | 
| Proportion of patients with IHC>0<1+ or IHC null (no stain at all) HER2 expression | Proportion of patients with IHC>0<1+ or IHC null (no stain at all) HER2 expression among previously identified HER2-negative locally-advanced or mBC patients based on rescoring of archived IHC-stained FFPE slides | 6 months from the Last subject In | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sociodemographic (age, gender, smoking status, country, ethnicity, site type [community hospital, academic hospital, biobank, research institute], family history of BC) and clinical pathological characteristics | Menopausal status Age at initial diagnosis of BC Eastern Cooperative Oncology Group (ECOG) performance status (0 = fully active to 4 = completely disabled) at index date Tumor, nodes, metastases (TNM) staging at initial diagnosis of BC and locally-advanced or mBC stage Tumor grade at first diagnosis, and at index date (if available) HR status (ER/PR - positive/negative) BRCA mutation status Histological type (ductal, lobular, mixed, other) Comorbidities (diabetes mellitus, hypertension, cardiovascular disease, osteoporosis) Treatment for early-stage BC with duration (if available) Locoregional treatment received (yes/no) after index date • Diagnostic tests/investigations (radiological, laboratory) Oncotype or MammaPrint status/results (if available) • Endocrine refractory/sensitive status (if available) • Date of diagnosis and duration of each LOT in locally-advanced or mBC setting | 6 months from the Last subject In | 
| Proportions of patients in the overall study population and each study subset receiving the following treatments for early-stage BC (if available), locally-advanced or mBC | Anti-HER2 targeted therapy ([Antibody: trastuzumab, pertuzumab], [ADC: trastuzumab emtansine, T-DXd], [tyrosine kinase inhibitor: lapatinib, neratinib, and tucatinib]) Standard chemotherapy Hormonal/endocrine therapies (aromatase inhibitor, alpelisib, ethinyl estradiol, fluoxymesterone, megestrol acetate, fulvestrant [selective ER degrader, SERD], tamoxifen) Immunotherapy Targeted therapy (CDK4/6 inhibitor, everolimus, AKT inhibitor) Other | 6 months from the Last subject In | 
| Clinical outcomes | Following outcomes for locally-advanced or mBC in the overall study population and HER-2 subsets identified after rescoring (HER2 low-IHC1+ or IHC2+/ISH-, HER2 IHC>0<1+; HER2 null, and HER2 zero-HER2 IHC>0<1+ and HER2 null). (a) Median OS Following outcomes will also be assessed by each LOT (b) Median TFST and Median TTD (c) Median rwPFS (d) rwORR | 6 months from the Last subject In | 
| Concordance between rescoring IHC status as HER2-low by central laboratory and/or local laboratory | Historical scoring and local laboratory rescoring of HER2 IHC status | 6 months fromthe last subject In | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subsets, ISH: in situ hybridization, Prognostic and Predictive Biomarker, Formalin-fixed, paraffin-embedded (FFPE), endocrine therapy(ET), HER2 Low, Metastatic breast cancer, HR:Hormone Receptor, IHC:mmunohistochemistry, Anticancer therapy