Real-World Treatment Patterns and Outcomes in HER2-Altered Metastatic Breast Cancer Patients in the United States

Real-World Treatment Patterns and Outcomes of Patients With HER2-Altered Metastatic Breast Cancer in the United States

This study aims to address the following key objectives in patients with HER2-altered mBC:

Primary objectives

• Estimate the prevalence of human epidermal growth factor receptor 2 positive (HER2+), human epidermal growth factor receptor 2 (HER2) mutation, cooccurrence of HER2+ and HER2 mutation among adult patients with metastatic breast cancer (mBC)

• Among mBC patients with HER2+ and HER2 mutation, describe the following:

  • Baseline demographic and clinical characteristics
  • Treatment patterns during follow-up including 1L through fifth-line (5L) settings
  • Real-world overall survival (rwOS) for 1L through 5L

Secondary objectives

- Among mBC patients with HER2+ and HER2 mutation, examine the following (as permissible in the study data):

• Real-world progression-free survival (rwPFS)
• Real-world time to discontinuation (rwTTD)
• Real-world time to next treatment (rwTTNT)
• Real-world overall response rate (rwORR)

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer

• Study Type: Observational
• Enrollment (Estimated): 7933

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Ridgefield, Connecticut, United States, 06877
      • Ridgefield

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (>=18 years) with confirmed diagnosis of recurrent or de novo metastatic breast cancer (mBC) who were diagnosed between January 1, 2018, through March 31, 2024 (1 year prior to the data cutoff date, March 31, 2025) in the Flatiron Solid Tumor Discovery Clinico-Genomic Database (CGDB).

Description

Inclusion criteria:

Overall metastatic breast cancer (mBC) cohort (total population):

• Histologically or cytologically confirmed diagnosis of breast cancer (BC)
• Patient has at least 2 documented clinical visits in the Flatiron network, on different days, during the study period from 1 January 2011 through 31 March 2025

• Initial diagnosis of de novo or recurrent mBC established during the case selection window from 1 January 2018 through 31 March 2024 (1 year prior to the data cutoff date, 31 March 2025)

  -- The date of initial mBC diagnosis will define the study index date

• Aged ≥ 18 years at the study index date

Human epidermal growth factor receptor 2 (HER2)-positive subcohort (mBC HER2+):

• Patients meeting eligibility for the mBC cohort
• Patients can be HER2-mutant or HER2 nonmutant

• Evidence of HER2+ as defined by immunohistochemistry (IHC)/in situ hybridization (ISH) based on a test performed within 180 days before or 180 days after the index date. If a patient does not have any IHC/ISH test during the 180-day periods before or after the index date, then tests performed at any time in the pre-index date period will be examined and any evidence of HER2+ status will classify the patient as HER2+.

  • IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH or ISH+ (without further information on IHC) according to American Society of Clinical Oncology/College of American Pathologists guidelines.
  • The sample date will be used to define biomarker status. If the sample date is missing, the report date will be used.

HER2-mutant subcohort (mBC HER2-mutant):

• Patients meeting eligibility for the mBC cohort
• HER2-mutant: Patients are classified as having an HER2 mutation if there is evidence of NGS short variant alterations at any time in the database, regardless of the functional type, which includes missense, nonsense, frameshift, nonframeshift, or splice variants.

Exclusion criteria

mBC cohort (total population):

-To ensure adequate treatment and outcome data, any patient without a visit or medication record (i.e., medication order/administration or LOT) within 90 days of mBC diagnosis (i.e., the time window from 90 days before to 90 days after the mBC diagnosis).

HER2+ subcohort (mBC HER2+):

- None (other than those applicable for the mBC cohort).

HER2-mutant subcohort (mBC HER2-mutant):

- Patients who are included in the HER2+ subcohort.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Metastatic breast cancer cohort (mBC); Adult patients (>=18 years) with confirmed diagnosis of recurrent or de novo metastatic breast cancer (mBC) who were diagnosed between January 1, 2018, through March 31, 2024 (1 year prior to the data cutoff date, March 31, 2025) in the Flatiron Solid Tumor Discovery Clinico-Genomic Database (CGDB).
HER2-positive subcohort (mBC HER2+); Patients meeting eligibility of the mBC cohort. Evidence of HER2 positive (HER2+) as defined by immunohistochemistry (IHC)/in situ hybridization (ISH); IHC 3+ or; IHC 2+ and evidence of HER2 amplification by ISH or; ISH+ without further information on IHC.
HER2-mutant subcohort (mBC HER2-mutant); Patients meeting eligibility of the mBC cohort. Evidence of NGS short variant alterations at any time in the database, regardless of the functional type, which includes missense, nonsense, frameshift, nonframeshift, or splice variants. Patients who are not included in the HER2+ subcohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world overall survival (rwOS)	OS as an event for each patient will be defined as the date of death minus the index date + 1. For patients with no record of death, OS will be censored at the last visit date, defined as the date of the last visit of any type prior to data cutoff. Month and year of death are noted in the Flatiron Discovery Clinico-Genomic Database (CGDB); the day of death will be imputed as the midpoint (15 th) of the month of death. Endpoint will be assessed separately from the study index date (mBC diagnosis) and each of the line of therapy (LOT) index dates.	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world time to treatment discontinuation (rwTTD)	rwTTD is defined as the time from the LOT start date to the end of the LOT + 1 (inclusive of maintenance therapies associated with the main therapeutic regimen). End of LOT will be defined as a composite of discontinuation (with or without subsequent LOT) or death. Patients on treatment at the end of the study period will be censored at that date.	Up to 15 years
Real-world time to next treatment (rwTTNT)	rwTTNT is defined as the difference between subsequent LOT index dates (e.g., time from the 1L start date to the 2L start date, time from 2L start date to the 3L start date). Patients not receiving a subsequent treatment line will be censored at the last visit date.	Up to 15 years
Real-world overall response rate (rwORR)	rwORR will be computed as the proportion of patients who achieved either a complete response or a partial response at any time during the therapy line. Distribution of best responses will be reported only for patients with known clinical responses (excluding unknown and missing/not available) for each treatment line. Endpoint will be assessed separately for each LOT.	Up to 15 years
Real-world progression-free survival (rwPFS)	rwPFS will be defined as the difference between the index date and first record of disease progression or death after the index date + 1. For patients with no record of disease progression, rwPFS will be censored at the start of a subsequent LOT or the date of the last clinical note before the end of the study period, whichever is earlier. Endpoint will be assessed separately from each of the LOT index dates.	Up to 15 years

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Actual): January 15, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

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: 1479-0045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore, limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency