Could You Be Eligible for New Targeted Breast Cancer Treatments? Here’s What 2025 Breakthroughs Mean for You

In 2025, breast cancer treatments in the US are increasingly personalized according to the tumor’s specific molecular markers, such as HER2 status (including HER2-positive, HER2-low, and HER2-ultralow), hormone receptor (HR) status, and for some patients, triple negative biology. Updates in FDA approvals, targeted agents, and clinical studies have influenced the standard of care for various breast cancer subtypes, with many patients experiencing improved progression-free survival and quality of life.

Advances for HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer

HER2 status testing has undergone significant refinement, enabling more precise treatment recommendations. In addition to therapies for traditional HER2-positive cancers, recent approvals have broadened options for patients previously classified as HER2-negative.

Enhertu for HER2-Low and HER2-Ultralow Breast Cancer

Enhertu (trastuzumab deruxtecan) was FDA-approved in 2025 for:

• Adults with unresectable or metastatic HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer
• Patients whose disease has progressed after at least one prior endocrine therapy

Highlights from DESTINY-Breast06 trial:

• Median progression-free survival (PFS): 13.2 months with Enhertu compared to 8.1 months with chemotherapy
• Objective response rate (ORR): 62.6% for Enhertu versus 34.4% for chemotherapy
• Consistency: Benefits also observed in HER2-ultralow populations (patients previously considered HER2-negative)

Eligibility and Next Steps:

• All metastatic breast cancer patients can consider updated HER2 testing (FDA-approved immunohistochemistry [IHC]), even after previous “HER2-negative” results. Patients with low or minimal HER2 expression may qualify for targeted therapies.
• HER2-positive brain metastases: Clinical data indicate Enhertu has efficacy for some patients with brain involvement.

Emerging Antibody-Drug Conjugates (ADCs) and Pipeline Therapies

For cancers that progress after Enhertu or standard therapies, clinical trials in 2025 are evaluating promising agents:

• ARX788, SHR-A1811, GQ-1005, and disitamab vedotin: These investigational therapies are being studied for HER2-positive, HER2-low, and patients with prior exposure to Enhertu. Early results show activity in brain and liver metastases and indicate favorable safety profiles, but broader use awaits further validation.
• Additional approaches: Early-stage development includes bi-specific antibodies and small molecule conjugates intended to address a wider range of patients, with ongoing research into minimizing side effects.

Evolving Hormone-Positive (HR+/HER2-) Breast Cancer Treatments

Endocrine therapies continue to be fundamental for HR+ breast cancer, though resistance may develop over time. The current landscape features:

CDK4/6 Inhibitors and Combination Strategies

• Kisqali (ribociclib) and similar CDK4/6 inhibitors: FDA-approved for certain early-stage and metastatic breast cancer patients, often used in combination with aromatase inhibitors.
• Ongoing research: Studies are testing new therapy combinations, including next-generation SERDs and strategies in resistant disease, with the goal of extending remission periods and postponing chemotherapy when possible.

Next-Generation SERDs and PROTACs

• Imlunestrant: An oral SERD that, according to pivotal EMBER3 trial data, has demonstrated improved outcomes in estrogen receptor–positive disease, notably for ESR1 mutations. Approval is anticipated, potentially providing a daily pill alternative to injectable SERDs.
• PROTACs (e.g., vepdegestrant): These therapies are designed to degrade estrogen receptors to address resistance mechanisms. Currently under evaluation with FDA Fast Track status, they may play a role as frontline or subsequent therapies pending further study results.

Other Targeted Treatments:

• PI3K and AKT inhibitors, PARP inhibitors: These targeted therapies are options for select patients with gene mutations (such as PIK3CA or BRCA mutations), complementing existing treatment paths for eligible individuals.

Triple-Negative Breast Cancer (TNBC): Recent Developments and Ongoing Research

Recent data from 2025 highlight continued research in TNBC, although fewer new approvals have been made compared to other subtypes:

• Standard treatment: Chemotherapy combined with immunotherapy (e.g., immune checkpoint inhibitors) remains standard for eligible advanced or metastatic TNBC cases.
• Emerging therapies: Agents such as Datroway (TROP2-directed ADCs) are under evaluation and may impact future progression-free survival rates as research continues.
• Clinical trials: Ongoing studies combining chemotherapy, immunotherapy, and new ADCs may expand options for TNBC patients in the near future.

Managing Advanced and Metastatic Breast Cancer: Individualized Approaches

For those with metastatic or treatment-resistant breast cancer:

• Recommended steps in 2025:
• Re-evaluate tumor HER2 and HR status, particularly if the initial assessment occurred several years prior.
• Consult with a multidisciplinary oncology team to determine eligibility for next-generation ADCs, oral SERDs, or suitable clinical trials.
• Consider treatment de-escalation strategies when supported by clinical evidence, and discuss new therapies as emerging data allow.

Cost and Access: FDA-approved therapies are frequently covered by insurance, though benefit levels may differ. For new or investigational options, coverage might be limited or require appeals. Financial assistance programs and nonprofit organizations can provide information on support resources for eligible patients.

Looking Ahead: More Personalized and Tolerable Options

Looking to 2025 and beyond, breast cancer management is shifting toward more individualized, targeted, and less toxic approaches. HER2 and hormone receptor testing, including newer distinctions like “low” and “ultralow” HER2, alongside genetic screening, are important for guiding treatment. The expansion of next-generation ADCs and hormone therapies is creating new opportunities, while clinical trial participation is encouraged for those interested in contributing to and accessing innovative treatment modalities.

Sources

• Top Breast Cancer Research in 2024 – Breastcancer.org
• Enhertu approved in the US for HER2-low or ultralow breast cancer after endocrine therapy – AstraZeneca
• SABCS 2024: Promising Breast Cancer Treatments and Approaches – BCRF

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