2025’s Breakthrough Breast Cancer Treatments: What New Approaches Mean for Your Care and Outcomes

In 2025, breast cancer treatments in the US are highly personalized and depend on the molecular subtype of the tumor—whether it is triple negative, hormone receptor positive, HER2-positive, or HER2-low. Recent advances include antibody-drug conjugates (ADCs), next-generation hormone and targeted therapies, and expanded use of immunotherapy for select patients. Below, the latest standards and emerging options for each major subtype are outlined, including chemotherapy, immunotherapy, HER2-directed therapy, and hormone therapy, as well as innovations for metastatic and advanced disease.

Chemotherapy for Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) refers to tumors lacking estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. Chemotherapy is a primary approach for both early-stage and metastatic TNBC. Standard regimens typically include:

• Anthracyclines and taxanes (doxorubicin, paclitaxel, etc.) as commonly used agents.
• Neoadjuvant chemotherapy (chemotherapy before surgery) is routinely offered in higher-risk, early-stage TNBC, with the pathologic response guiding subsequent therapy decisions.
• For metastatic TNBC, patients whose tumors express PD-L1 (a biomarker) may be eligible for immunotherapy with pembrolizumab (Keytruda) combined with chemotherapy, currently the only checkpoint inhibitor FDA-approved specifically for breast cancer.

While ongoing research explores immunotherapy combinations, immunotherapy with chemotherapy outside PD-L1-positive TNBC is not currently standard for HER2-positive or hormone receptor-positive subtypes [1][2].

Hormone Therapy for Hormone Receptor-Positive Breast Cancer

Hormone (endocrine) therapies are a cornerstone for HR-positive, HER2-negative breast cancers, the most common subtype (about 70% of cases): - Aromatase inhibitors (letrozole, anastrozole, exemestane), tamoxifen, and fulvestrant (Faslodex) are frequently used and are tailored to menopausal status and other risk factors. - Oral selective estrogen receptor degraders (SERDs) such as elacestrant (Orserdu) provide an additional option, particularly after menopause or after resistance to other endocrine agents. - CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are commonly combined with hormone therapies for advanced or metastatic disease and have been shown to delay disease progression and reduce the need for chemotherapy. - Targeted agents: For tumors with PI3K/AKT pathway mutations, agents like alpelisib (Piqray) or capivasertib (Truqap) are used in combination with hormone therapy where indicated. - Research directions: Next-generation agents such as CDK7 inhibitors and other SERDs are under study in clinical trials, seeking to expand available treatment choices.

Advances in HER2-Directed Therapies

HER2-Positive (IHC 3+ or ISH+)

HER2-positive breast cancer is treated with therapies that specifically target the HER2 protein:

• Trastuzumab (Herceptin) and pertuzumab (Perjeta) are used in combination with chemotherapy for early and metastatic disease.
• Antibody-drug conjugates (ADCs), including trastuzumab emtansine (T-DM1, Kadcyla) and trastuzumab deruxtecan (Enhertu), are used after progression or in certain advanced cases. These medications deliver chemotherapy directly to HER2-expressing cells, helping to limit side effects to other tissues [2][3].
• Studies have reported median progression-free survival in metastatic HER2-positive disease now often exceeds one year with these approaches, with consistently high response rates.

HER2-Low and HER2-Ultralow

As of 2025, Enhertu (trastuzumab deruxtecan) has been approved for adults with metastatic, HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, after progression on at least one prior endocrine therapy. Data supporting this include [3]:

• Median progression-free survival of 13.2 months for those receiving Enhertu, versus 8.1 months for those on standard chemotherapy.
• Objective response rates exceeded 60%, compared to about 34% for chemotherapy.
• Eligibility depends on HER2 expression testing by FDA-approved assays; it is estimated that up to 85–90% of HR-positive, HER2-negative metastatic breast cancers may qualify as HER2-low or ultralow and thus become eligible for this therapy.

This expansion of treatment indications offers more options for those who may not have previously been considered for HER2-directed therapies.

Immunotherapy in HER2-Positive Metastatic Disease

Currently, immunotherapy (pembrolizumab) is FDA-approved only for select metastatic TNBC cases. It is not a standard of care for HER2-positive subtypes outside clinical trials, though ongoing research is evaluating combinations of HER2-targeted therapies and immunotherapy [2].

PARP Inhibitors and Targeted Approaches for Mutation-Driven Cancers

Patients with inherited BRCA1/2 or PALB2 mutations may benefit from PARP inhibitors:

• Olaparib (Lynparza) and talazoparib (Talzenna) are FDA-approved for individuals with advanced HER2-negative breast cancer and specific genetic backgrounds.
• These drugs are often used after other standard therapies, such as anthracycline/taxane chemotherapy, or when standard endocrine/HER2-directed agents are not effective.

For those with PI3K (PIK3CA) or AKT1/AKT pathway mutations, targeted therapies like alpelisib, capivasertib, and inavolisib (recent FDA approval in select settings) are now used alongside hormone therapy for appropriate HR-positive, HER2-negative breast cancers [2].

Multimodal and Individualized Treatment Strategies

• Local treatments, including surgery and radiation, remain important for patients with operable early-stage or select metastatic diseases.
• Systemic therapy selection factors include:
  • Tumor subtype (triple negative, HER2 status, hormone receptor status)
  • Specific gene mutations
  • Prior therapy responses and individual patient considerations

Advances in Care for Advanced and Metastatic Breast Cancer

Ongoing clinical trials in 2025 are exploring:

• New uses for immunotherapies beyond TNBC
• Next-generation ADCs for different patterns of HER2 expression
• Innovative combination therapies
• Monitoring of disease through “liquid biopsies” (circulating tumor DNA or cells)—currently under research and not yet part of routine care.

Participation in clinical trials may be recommended when existing treatments are not sufficient or in order to access investigational therapies [2]. Most large cancer centers can help patients identify trial opportunities.

Information on Access, Eligibility, and Cost

• Eligibility: Access to many therapies requires confirmation of tumor markers (ER, PR, HER2 via IHC/ISH, BRCA, and other gene testing).
• Cost and insurance: Most FDA-approved treatments are typically covered by insurance, but out-of-pocket costs, particularly for new ADCs, may vary. Financial counseling and pharmaceutical assistance programs may offer support.
• Clinical trials: Many studies cover the cost of the investigational drug; patients may still have costs related to standard care and potentially travel, depending on the specifics of the trial.

Looking Forward: The Evolving Landscape

Treatment approaches in 2025 are increasingly personalized, with greater numbers of patients now eligible for HER2-targeted therapies and expanding options for hormone-based and targeted treatments. Ongoing innovations in ADCs and other areas continue to contribute to improvements in care. Collaboration with multidisciplinary care teams and up-to-date molecular testing are important for accessing the most current and appropriate treatment options. Ongoing follow-up is recommended, as clinical standards continue to evolve with emerging research.

Sources

• National Cancer Institute: Breast Cancer Treatment (PDQ®)
• Susan G. Komen®: Emerging Areas in Research on Metastatic Breast Cancer Treatment
• AstraZeneca Press Release: Enhertu approved in the US as first HER2-directed therapy for HER2-low/ultralow metastatic breast cancer

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