HER2-negativeiRetroBCNCT06131424
NIS Study Determining Prevalence of HER2-low in Metastatic Breast Cancer Patients
An observational study of HER2-negative, run by AstraZeneca at 31 sites in 13 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-negative
- How many people
- 1,151 participants
- Where
- 31 sitesin 13 countries
- Study dates
- 23 Apr 2024to 19 May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Eligible patients from sites will be selected in a consecutive manner ie, patients with dates closest to but on or after 01 January 2019 will be selected first.
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
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Trial locations and contacts
31 sites in 13 countries.
31 sites in 13 countries
India10 sites
Research Site
Bengaluru, Karnataka, 560017
Research Site
Bhubaneswar, Odisha, 751003
Research Site
Delhi, 110005
Research Site
Delhi, 110029
Research Site
Delhi, 110085
Research Site
Hyderabad, Telangana, 500034
Research Site
Kochi, Kerala, 682041
Research Site
Mohali, Punjab, 160055
Research Site
Mumbai, Maharashtra, 400012
Research Site
Varanasi, Uttar Pradesh, 221005
Singapore4 sites
Research Site
Singapore, 168583
Research Site
Singapore, 229899
Research Site
Singapore, 258499
Research Site
Singapore, 308433
Malaysia3 sites
Research Site
Kaula Lumpur, 47500
Research Site
Subang Jaya, 47500
Research Site
Subang Jaya, 59100
Thailand3 sites
Research Site
Bangkok, 10330
Research Site
Bangkok, 10400
Research Site
Bangkok, 10700
Vietnam3 sites
Research Site
Hanoi
Research Site
Ho Chi Minh City
Research Site
Huế
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- HER2-negative
- Keywords
- HER2 Low, Metastatic breast cancer, HR:Hormone Receptor, IHC:mmunohistochemistry, ISH: in situ hybridization, Anticancer therapy, Prognostic and Predictive Biomarker, Formalin-fixed, paraffin-embedded (FFPE), endocrine therapy(ET), Subsets
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with IHC 1+ or IHC 2+/ISH- HER2 expression.
- 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.
Measured: 6 months from the Last subject In
Proportion of patients with HER2 ultra-low (IHC 0 (pattern 0+) with membrane staining ie, incomplete and faint/barely perceptible in ≤10% tumor cells) HER2 expression and IHC null (IHC 0 ie, absent membrane staining),
Proportion of patients with HER2 ultra-low (IHC 0 (pattern 0+) with membrane staining ie, incomplete and faint/barely perceptible in ≤10% tumor cells) HER2 expression and IHC null (IHC 0 ie, absent membrane staining), expanded biomarker association with HER2-low patient characteristics, change in HER2 and HR expressions between diagnosis and treatment, concordance of HER2 IHC scores between manual rescoring and digital scoring.
Measured: 6 months from the Last subject In
Secondary outcomes (4)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 6 months fromthe last subject In
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2023
- Study start23 Apr 2024
- Primary completion19 May 2025
- Study completion19 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-negativeStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,151 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06131424
- Sponsor's protocol ID
- D9673R00037
- Acronym
- iRetroBC
- Status last verified
- Sep 2025
- First submitted
- 9 Nov 2023
- Last updated
- 18 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06131424
- Acronym / sponsor ID
- iRetroBC / D9673R00037
- Conditions
- HER2-negative
- Keywords
- HER2 Low, Metastatic breast cancer, HR:Hormone Receptor, IHC:mmunohistochemistry, ISH: in situ hybridization, Anticancer therapy, Prognostic and Predictive Biomarker, Formalin-fixed, paraffin-embedded (FFPE), endocrine therapy(ET), Subsets
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,151 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 23 Apr 2024 (actual)
- Primary completion
- 19 May 2025 (actual)
- Study completion
- 19 May 2025 (actual)
- First posted
- 14 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible patients from sites will be selected in a consecutive manner ie, patients with dates closest to but on or after 01 January 2019 will be selected first.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Proportion of patients with IHC 1+ or IHC 2+/ISH- HER2 expression.
Time frame: 6 months from the Last subject In
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.
Proportion of patients with HER2 ultra-low (IHC 0 (pattern 0+) with membrane staining ie, incomplete and faint/barely perceptible in ≤10% tumor cells) HER2 expression and IHC null (IHC 0 ie, absent membrane staining),
Time frame: 6 months from the Last subject In
Proportion of patients with HER2 ultra-low (IHC 0 (pattern 0+) with membrane staining ie, incomplete and faint/barely perceptible in ≤10% tumor cells) HER2 expression and IHC null (IHC 0 ie, absent membrane staining), expanded biomarker association with HER2-low patient characteristics, change in HER2 and HR expressions between diagnosis and treatment, concordance of HER2 IHC scores between manual rescoring and digital scoring.
4 secondary outcomes
Sociodemographic (age, gender, smoking status, country, ethnicity, site type [community hospital, academic hospital, biobank, research institute], family history of BC) and clinical pathological characteristics
Time frame: 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
Time frame: 6 months from the Last subject In
Clinical outcomes
Time frame: 6 months from the Last subject In
Concordance between rescoring IHC status as HER2-low by central laboratory and/or local laboratory
Time frame: 6 months fromthe last subject In
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
31 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HER2-negative, run by AstraZeneca at 31 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in India, Singapore, Malaysia, Thailand, Vietnam and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with IHC 1+ or IHC 2+/ISH- HER2 expression. (time frame: 6 months from the Last subject In). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.