UNFOLD Study Egypt

A Multicenter, Observational, Secondary Data Collection, Retrospective, National Study to Assess the Prevalence of HER2-low Breast Cancer Among Patients Previously Diagnosed With Unresectable and/or Metastatic HER2-Negative Breast Cancer in Egypt - UNFOLD

Breast cancer is a major public health concern worldwide. In Egypt, it was the most diagnosed cancer among females in 2020 with an incidence rate of 32.4%. Its age-standardized incidence and mortality rates were 48.7 and 20.4 per 100,000 population, respectively. The status quo of HER2 testing in Egypt is that all breast cancer cases are tested for HER2 protein expression on the surface of tumor cells by immunohistochemistry (IHC), and only those with score 2 (equivocal) and selected cases of score 3 are subjected for further analysis using in-situ hybridization technique (ISH) to detect HER2 gene amplification in tumor nuclei.

Study Overview

• Status: Completed
• Conditions: Breast Cancer

Detailed Description

Besides its role in the prognostic assessment of breast cancer, accurate determination of HER2 status is critical for appropriate selection of eligible patients for targeted therapy. In 2018, the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) had a revised guideline for HER2 testing in breast cancer. Breast cancers were traditionally classified as HER2-pos and HER2-neg. HER2-positive BCs are those with either IHC3+ -characterized as complete, intense circumferential membrane staining in >10% of cells-, or equivocal IHC (i.e., IHC2+) -characterized as weak to moderate/complete membrane staining in >10% of cells- and ISH+. While HER2-negative BCs were considered those with one of the following results: IHC0 (No staining or incomplete, faint/barely perceptible staining in ≤10% of cells), IHC1+ (No staining or incomplete, faint/barely perceptible staining in >10% of cells), or IHC2+ and ISH-. Recently, the HER2 categorization of BC has been differentiated into 3 subgroups: those with no detectable IHC staining (referred to herein as HER2 null), those with detectable HER2 staining in less than 10% of tumor cells (referred to herein as IHC>0<1+), and those with IHC1+ or IHC2+/ISH- results (collectively referred to herein as HER2-low). Little is known about the prevalence and clinical implications of HER2-neg BC subgroups that express low levels of HER2; these cancers have traditionally not been considered as separate subgroups and consequently there has been a lack of HER2-directed treatment options for these patients.

Treatment options for mBC depend on several factors including, but not limited to, the patient's overall health and the levels of hormone receptor (HR) and HER2 in the tumor. Current SoC that is based on HER2 expression only considers BCs as being either HER2-pos or HER2-neg. For HER2-pos cancers, therapies that target HER2 combined with chemotherapy or other anti-HER2 agents can significantly improve survival. Although there are no therapies specifically for patients with HER2-low BC, preliminary evidence has demonstrated antitumor activity of T-DXd, an anti-HER2 agent, in HER2-low BCs. Hence, applying the most recent cut-off values when testing for HER2 expression is critical for maximizing treatment benefit for the highest number of patients (HER2-low & HER2-pos).

This national, multicenter, non-interventional, secondary data collection, retrospective study aims to describe the prevalence of HER2-low BC in Egypt by accurate categorization of HER2 status in HER2 reports of patients previously determined as HER2-neg and analyzing the SoC and clinical outcomes of HER2-low patients from medical chart abstraction.

• Study Type: Observational
• Enrollment (Actual): 405

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Research Site
  • Asyut, Egypt
    • Research Site
  • Cairo, Egypt
    • Research Site
  • Gharbia, Egypt
    • Research Site
  • Giza, Egypt
    • Research Site
  • Luxor, Egypt
    • Research Site
  • Sohag, Egypt
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed diagnosis of HER2-negative, unresectable and/or mBC (regardless of HR status) between 01 January 2017 and 31 December 2020 who progressed on any systematic anticancer therapy (eg, ET, chemotherapy, CDK4/6i, targeted therapies other than anti-HER2, or immunotherapy). Patients' clinical outcomes will be followed up for 2 years after the date of their diagnosis.

Description

Inclusion Criteria:

1. Men or women ≥ 18 years of age,
2. Must have a histological, cytological, or radiological confirmed diagnosis of unresectable or/and mBC between 01 January 2017 and 31 December 2020, with at least 2 years of follow-up data unless patient's death is confirmed,
3. Diagnosed as HER2-neg (HER2 IHC 0, 1+, 2+/ISH-), regardless of hormone status,
4. Must have a report in her file with HER2 scoring with IHC/ISH or both,
5. Progressed on any systemic anti-cancer therapy (eg, ET, chemotherapy, CDK4/6i, targeted therapies other than anti-HER2, or immunotherapy) in the metastatic setting.
6. Due to the retrospective nature of the study a waiver grant of the consent will be requested from the IRB/IEC for the study participants, if waiver not granted Patient or next of kin/legal representative (for deceased patients at study entry) willing and able to provide written informed consent according to the local regulations.

Exclusion Criteria:

• Records of patients who meet any of the following criteria will be excluded:

  1. History of other malignancies than mBC,
  2. Historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HER2-low prevalence	HER2-low prevalence based on reviewing historical HER2 reports of HER2-neg mBC patients.	3 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HER2-low Breast Cancer Patient Baseline characteristics	Baseline characteristics for patients identified as having HER2-low BC.	3 Years
HER2 IHC Null Breast Cancer Patient Baseline Characteristics	Baseline characteristics for patients identified as having HER2 IHC Null BC.	3 Years
The overall prevalence of HER2-low among unresectable and/or mBC patients	The overall prevalence of HER2-low among unresectable and/or mBC patients identified as HER2-neg, regardless of assays used, will also be summarized descriptively for HR-pos and HR-neg population, respectively.	3 Years
Treatment patterns	Types of therapies for patients will be summarized descriptively for HR-pos and HR-neg population, respectively.	3 Years
HER2-low Breast Cancer Clinical presentation for patients	clinical presentation for patients identified as having HER2-low BC.	3 Years
HER2 IHC Null Breast Cancer clinical presentation for patients	clinical presentation for patients identified as having HER2 IHC Null BC.	3 Years
HER2-low Breast Cancer Patients Clinical outcomes	Clinical outcomes for patients identified as having HER2-low BC.	3 Years
HER2 IHC Null Breast Cancer Patients Clinical outcome	Clinical outcomes for patients identified as having HER2 IHC Null BC.	3 Years
Treatment Patterns	Duration on treatment therapies for patients will be summarized descriptively for HR-pos and HR-neg population, respectively.	3 Years

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSR Synopsis redacted

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2024
• Primary Completion (Actual): September 16, 2024
• Study Completion (Actual): September 16, 2024

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: D133FR00199

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No