Majority of HER2-Positive Breast Cancer Patients Miss Out on Standard Care, Study Finds
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Nearly two-thirds of patients diagnosed with HER2-positive metastatic breast cancer between 2015 and 2024 did not receive the guideline-recommended first-line treatment, a concerning trend linked to poorer outcomes and often influenced by factors like age and disease recurrence. The findings, presented at the San Antonio Breast Cancer Symposium in December 2025, underscore a significant gap between established medical guidelines and real-world clinical practice.
Real-World Data Reveals Treatment Disparities
Researchers at the Cleveland Clinic analyzed de-identified electronic health records to understand why patients often deviate from the preferred initial regimen of taxane, Herceptin (trastuzumab), and Perjeta (pertuzumab) – commonly known as THP. The retrospective study, detailed in a recent Cleveland Clinic publication, examined the records of 3,277 patients.
“We’ve got a first-line standard of care, but are patients even getting it in the real world?” stated a medical oncologist at the Cleveland Clinic Taussig Cancer Institute in a news release. “And if they’re not getting it because they’re recurrent breast cancers or can’t tolerate chemotherapy, that could be a reason they should be getting a more novel approach like an antibody drug conjugate.”
THP Underutilized Despite Proven Benefits
The analysis revealed that only 35.5% of patients received the THP regimen. The remaining 64.5% were treated with alternative approaches, including HER2-targeted therapy alone (17.1%) or a combination of HER2-targeted therapies (36.8%).
Patients who received the standard THP treatment experienced significantly improved outcomes. The median time to needing a third-line treatment or death was 30.1 months for those on THP, compared to just 17.4 months for those receiving alternative regimens. Furthermore, median progression-free survival through the second line of treatment was 26.1 months with THP, versus 18.9 months with alternative therapies.
Patient Characteristics Influence Treatment Decisions
The study highlighted that specific disease characteristics played a crucial role in treatment selection. Patients receiving alternative therapies were more likely to have hormone receptor-positive (HR+) status (74.9% versus 61.1% in the standard care group) and evidence of cancer spreading to the brain (11.1% versus 7.6%).
A patient’s history also proved significant. Over half (57.2%) of those receiving alternative therapies had recurrent cancer, meaning they had previously been treated for an earlier stage of the disease. In contrast, only 34.5% of patients in the standard care group had recurrent disease, with the majority (61.3%) receiving a “de novo” stage 4 diagnosis.
Collaborative Study Leverages Broad Dataset
This large-scale observational study was a collaborative effort between the Cleveland Clinic and AstraZeneca Pharmaceuticals. Researchers analyzed data from the Flatiron Health database, encompassing electronic health records from over 280 oncology clinics across the United States. Approximately 75% of the patients included in the study received care in community-based settings, providing a representative picture of cancer treatment across the country.
To participate, patients needed a confirmed HER2-positive biomarker test result prior to initiating first-line treatment between January 2015 and February 2024. Patient progress was then tracked through September 2024. Standard of care was defined as THP followed by maintenance Herceptin and Perjeta, with endocrine therapy added for HR-positive disease. During the follow-up period, 32.9% of those on standard care progressed to a third-line treatment, while 26.5% died. Among those on alternative regimens, 37.1% moved to a third-line treatment and 33.3% died.
Safety Concerns and Alternative Approaches
Researchers identified several safety factors influencing treatment choices. Patients in the alternative therapy group were, on average, older (61.4 years) than those receiving standard care (58.7 years). A senior author noted that some patients may be unable to tolerate the intensive chemotherapy required by the THP regimen.
Specific concerns included pre-existing conditions like neuropathy, general frailty, a high risk of side effects, and prior exposure to similar treatments. A small percentage (3%) of patients in the alternative therapy group had a performance status score indicating significant impairment in daily activities, compared to 1.5% in the standard care group. Notably, a substantial proportion (43.1%) of the alternative therapy group had an unknown or undocumented performance status at the start of treatment.
The researchers suggest that newer treatments, such as antibody-drug conjugates, may be appropriate for patients who cannot tolerate standard chemotherapy or experience rapid disease recurrence.
This study underscores the need for a more nuanced approach to HER2-positive metastatic breast cancer treatment, balancing adherence to guidelines with individualized patient considerations to optimize outcomes.
