Most Patients With HER2+ Breast Cancer Miss Standard Treatment, Study Shows

Cleveland Clinic researchers have found that nearly two-thirds of patients with HER2-positive metastatic breast cancer did not receive the guideline-recommended standard of care treatment between 2015 and 2024, a decision often driven by age and disease recurrence that resulted in shorter times to disease progression.

The study, findings of which were presented at the San Antonio Breast Cancer Symposium in December 2025, used real-world data to examine why patients receive alternative therapies instead of the preferred first-line regimen of taxane, Herceptin (trastuzumab) and Perjeta (pertuzumab), known as THP.

“We’ve got a first-line standard of care, but are patients even getting it in the real world? 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," Dr. Azka Ali, a medical oncologist at the Cleveland Clinic Taussig Cancer Institute, stated in a news release from the institution.

Main data that support the findings

The retrospective analysis, which was detailed in an article published by the Cleveland Clinic, revealed a significant gap between medical guidelines and clinical practice. While THP is the established first-line standard of care, only 35.5% of the 3,277 patients in the study received it. The remaining 64.5% of patients were treated with alternative regimens. Within that group, 17.1% received HER2-targeted therapy alone and 36.8% received a combination of HER2-targeted therapies.

Patients who received the standard THP regimen experienced significantly better long-term outcomes than those on alternative treatments. The median time to third-line treatment or death was 30.1 months for those receiving standard care, compared to 17.4 months for those receiving other regimens.

Furthermore, the study measured real-world progression-free survival through the second line of treatment. Patients who started on the standard THP regimen had a median progression-free survival of 26.1 months. In contrast, patients who began with alternative therapies saw a median progression-free survival of 18.9 months.

Researchers noted that patient outcomes were closely tied to the specific characteristics of their disease at the time treatment began. 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 were more likely to have cancer that had spread to the brain (11.1% versus 7.6%).

The timing of the diagnosis also played a major role in which treatment a patient received. In the group receiving alternative therapies, 57.2% of patients had recurrent cancer, meaning they had been previously treated for an earlier stage of breast cancer before it returned as metastatic disease. In the standard care group, only 34.5% had recurrent disease, while 61.3% were "de novo" cases, meaning the cancer was already stage 4 at the time of their first diagnosis.

Trial details

This large-scale observational study was a collaboration between Cleveland Clinic and AstraZeneca Pharmaceuticals. To capture a "real-world" picture of cancer care, researchers analyzed de-identified electronic health records from the Flatiron Health database.

The study population included 3,277 patients aged 18 and older who were treated for HER2-positive metastatic breast cancer at more than 280 oncology clinics across the United States. The data reflects a broad cross-section of care, as approximately 75% of these patients were treated in community-based settings rather than major academic medical centers.

To be included in the analysis, patients must have had a confirmed HER2-positive biomarker test result before starting their first-line treatment between January 2015 and February 2024. Researchers followed the patients' progress through September 2024.

Standard of care was strictly defined as the use of THP followed by maintenance Herceptin and Perjeta, with the addition of endocrine therapy for those with HR-positive disease. The researchers monitored how many patients eventually moved to a third line of treatment or passed away. Among those who started on standard care, 32.9% moved to a third-line treatment and 26.5% died during the follow-up period. Among those on alternative regimens, 37.1% moved to a third-line treatment and 33.3% died.

Safety

While the study focused on treatment patterns and survival outcomes, researchers identified several health and safety factors that likely influenced why doctors chose alternative regimens over the standard of care.

Patients in the alternative therapy group were generally older, with a mean age of 61.4 years compared to 58.7 years for those receiving standard care. Senior author Dr. Azka Ali noted that some patients may not be able to tolerate the intensive chemotherapy required by the standard THP regimen.

Specific safety concerns that may make standard chemotherapy unsuitable for certain patients include:

• Pre-existing conditions such as neuropathy (nerve damage)
• General frailty or a lower performance status
• High risk of side effects
• Prior exposure to similar treatments during earlier stages of cancer

In the alternative treatment group, 3% of patients had a performance status score indicating significant impairment in daily activities, compared to 1.5% in the standard care group. Additionally, a much higher percentage of patients in the alternative group (43.1%) had an unknown or undocumented performance status at the start of treatment.

The researchers suggested that if patients cannot tolerate standard chemotherapy or if their cancer has returned quickly after previous treatments, they may be candidates for newer approaches, such as antibody-drug conjugates, earlier in their care.

References:

1. “Real-World Data Reveals Gap Between Guidelines and Practice in HER2+ Breast Cancer Care,” news release; https://consultqd.clevelandclinic.org/real-world-data-reveals-gap-between-guidelines-and-practice-in-her2-breast-cancer-care
2. “Long-term outcomes of first-line (1L), guideline-recommended treatment versus alternative regimens in HER2+ metastatic breast cancer (mBC): a retrospective observational study of US electronic health records” by Maki Inoue-Choi et al., presented at the San Antonio Breast Cancer Symposium.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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