Breakthrough Treatments for Advanced Breast Cancer in 2025

Latest breakthroughs in the treatment of breast cancer

By 2025, the domain of advanced breast cancer treatment is swiftly transforming, providing renewed optimism to patients globally. Recent advancements in precision medicine, targeted therapies, immunotherapy, and cellular treatments have equipped oncologists with an unprecedented array of tools to customize care and enhance survival rates.

New antibody-drug combinations, advanced CAR T-cell treatments, and AI-supported decision-making are changing previously untreatable conditions into ones that can be managed. This article examines the most promising and recent therapeutic options accessible in 2025 for individuals with advanced or metastatic breast cancer.

Latest therapies in 2025 for breast cancer treatment

I. Endocrine therapy

The treatment of ER+, PR+, HER2 0 breast cancer is based on endocrine therapy. Early-stage patients pursue a cure through surgery combined with adjuvant therapy, while advanced-stage patients prolong survival and improve quality of life through endocrine therapy combined with targeted therapy.

Treatment should be individualized according to the stage, molecular characteristics, and patient status, with attention paid to drug side effects and long-term management.

II. Treatment of Advanced Breast Cancer (Recurrent/Metastatic)

1. First-line Therapy: Endocrine Therapy Combined with Targeted Drugs

• Principle: Prioritize endocrine therapy to avoid excessive chemotherapy, unless the tumor progresses rapidly or shows endocrine resistance.
• Regimen Selection:
◦ CDK4/6 Inhibitors + Endocrine Therapy (Current Standard Regimen):
▪ Drugs: Palbociclib, Abemaciclib, Ribociclib (oral targeted drugs that inhibit the cell cycle and prolong survival).
▪ Combination Regimens:
• Premenopausal patients: CDK4/6 inhibitor + tamoxifen + ovarian function suppression (OFS), or CDK4/6 inhibitor + aromatase inhibitor (AI) + OFS.
• Postmenopausal patients: CDK4/6 inhibitor + AI (e.g., letrozole), or CDK4/6 inhibitor + fulvestrant (estrogen receptor antagonist).
◦ Fulvestrant monotherapy: Indicated for patients with failed endocrine therapy or AI resistance.
◦ Other targeted combinations:
▪ For patients with PIK3CA mutations: alpelisib + fulvestrant (targeting PI3K-AKT pathway mutations).
▪ mTOR inhibitors, such as everolimus, can be combined with aromatase inhibitors (AIs) for patients who are resistant to AIs; however, the side effects, including stomatitis and pneumonia, require careful monitoring.

III. Second-line and Subsequent Therapies

• Adjustment of endocrine therapy: Switch to different types of endocrine drugs (e.g., switch to AI after tamoxifen resistance, or switch to fulvestrant after AI resistance).
• Chemotherapy: We can select single-agent or combination chemotherapy (e.g., paclitaxel, capecitabine, gemcitabine) for patients with failed endocrine therapy and rapid tumor progression.
• Novel targeted drugs for ESR1 mutations include investigational estrogen receptor degraders, such as Giredestrant.
Some patients have attempted immunotherapy, combining PD-1 inhibitors with chemotherapy, but the evidence for this approach remains limited.

3. Supportive Therapy and Symptomatic Management

• Bone metastasis management: Bisphosphonates (e.g., zoledronic acid) or denosumab to prevent bone-related events (fractures, bone pain).
• Side effect management for endocrine therapy includes addressing hot flashes, osteoporosis (by supplementing with calcium and vitamin D and using zoledronic acid if necessary), and dyslipidemia. CDK4/6 inhibitors can cause neutropenia, which requires regular blood count monitoring, as well as fatigue.

III. Special Populations and Precautions
• Menopausal status assessment:
◦ Premenopausal: Normal menstrual cycle, low FSH level; postmenopausal: The menopause lasts less than 12 months, and the FSH level rises.

Pregnancy-associated breast cancer:

Avoid endocrine therapy during pregnancy (tamoxifen is teratogenic); treatment can begin after delivery.
• Genetic testing: Advanced patients are recommended to test for gene mutations such as PIK3CA, ESR1, BRCA1/2 to guide targeted therapy.
• Follow-up: Regular reviews of breast ultrasound, chest CT, bone scan, etc., to monitor recurrence and metastasis.

IV. Treatment Advances and Cutting-edge Directions

• New indications for CDK4/6 inhibitors: Approved for adjuvant therapy in high-risk early-stage patients (e.g., abemaciclib).
• Epigenetic therapy: Clinical trials of HDAC inhibitors combined with endocrine therapy are ongoing.
• Personalized medicine: Monitor tumor mutations via liquid biopsy (ctDNA) to dynamically adjust treatment regimens.

V. CAR-T therapy

BZD1901: A Breakthrough CAR-T Therapy Targeting Mesothelin-Positive Advanced Solid Tumors

BZD1901 is the first CAR-T drug that can release its own PD-1 nanobody and is made to treat advanced solid tumors that have mesothelin, which is found in about 50% of these tumors. Clinical trials have proven its remarkable efficacy, signaling a significant milestone in the group’s Bai Ze Plan and ushering in a new phase of cellular therapy development.

Key Clinical Findings

Data from investigator-initiated non-registered clinical studies (conducted in compliance with Good Clinical Practice, GCP) revealed:

• 100% Disease Control Rate (DCR) in 11 malignant mesothelioma patients, with 63.6%
• Objective Response Rate (ORR)
• 1 complete response (CR): Sustained CR for 24 months
• 6 partial responses (PR): Post-infusion tumor regression
• No severe adverse events were reported during the trials, highlighting its safety profile

Milestones and Publications

Scientific Rationale and Therapeutic Potential

Mesothelin Targeting: Various malignancies, such as lung, gastric, pancreatic, ovarian, and breast cancers, as well as mesothelioma, widely express mesothelin. This broad expression makes BZD1901 a promising therapy for multiple solid tumors.
The self-releasing PD-1 nanobody helps CAR-T cells last longer and work better against tumors by fighting off environments that suppress the immune system.

Innovation in Solid Tumor Therapy

The complete disease control rate and high overall response rate in mesothelioma patients show that BZD1901 could effectively address problems in solid tumor immunotherapy, like low T-cell presence and immune evasion.

Future Directions

BZD1901’s success paves the way for personalized cancer treatments. Ongoing research is intended to investigate new uses for BZD1901 in other tumors that have mesothelin and to improve treatment combinations with immune checkpoint inhibitors or chemotherapy. The group’s Bai Ze Plan aims to make advanced cellular therapies accessible to 60% of cancer patients within a decade, aligning with global efforts to improve cancer survival rates.