Overview: A New Era in Advanced Breast Cancer Care

In 2025, the treatment of advanced breast cancer is undergoing a revolutionary transformation. Driven by advances in precision medicine, targeted therapies, immunotherapy, and cellular treatments, patients with metastatic and recurrent breast cancer now have access to highly personalized and effective treatment options.

From AI-assisted decision-making to novel CAR T-cell therapies, these innovations are reshaping the clinical landscape and offering renewed hope for long-term disease control and improved quality of life. This article provides a comprehensive overview of the most promising therapeutic breakthroughs available in 2025 for advanced and metastatic breast cancer.

Latest 2025 Therapeutic Approaches for Advanced Breast Cancer

I. Endocrine Therapy for Hormone Receptor-Positive (HR+) Breast Cancer

For patients with ER+/PR+/HER2- breast cancer, endocrine therapy remains the cornerstone of treatment, particularly in early-stage disease and in metastatic settings.

• Early-stage: Surgical intervention followed by adjuvant endocrine therapy.
• Advanced-stage: Prolonging survival and maintaining quality of life through endocrine therapy plus targeted agents.

Key Principles:

• Tailor treatment based on tumor biology, molecular characteristics, menopausal status, and patient comorbidities.
• Monitor for adverse effects and adjust treatment for long-term management.

II. First-Line Therapy for Recurrent or Metastatic Breast Cancer

Endocrine Therapy Plus Targeted Therapy

Goal: Delay or avoid chemotherapy, especially for patients without visceral crisis or rapid disease progression.

Preferred Regimen: CDK4/6 Inhibitors + Endocrine Therapy

• CDK4/6 inhibitors: Palbociclib, Abemaciclib, Ribociclib
• Combination Regimens:
  • Premenopausal: CDK4/6 inhibitor + Tamoxifen or Aromatase Inhibitor (AI) + Ovarian Function Suppression (OFS)
  • Postmenopausal: CDK4/6 inhibitor + AI (e.g., Letrozole) or Fulvestrant

Other Options:

• Fulvestrant Monotherapy: For patients with prior AI resistance.
• PIK3CA-mutated tumors: Alpelisib + Fulvestrant.
• mTOR inhibitors (e.g., Everolimus): For AI-resistant cases. Requires monitoring for pneumonitis and mucositis.

III. Second-Line and Later Therapies

• Sequential Endocrine Therapy: Switch agents upon resistance (e.g., AI → Fulvestrant).
• Chemotherapy: Used when endocrine therapy fails or rapid disease progression occurs. Options include:
  • Paclitaxel
  • Capecitabine
  • Gemcitabine
• Emerging Drugs:
  • Giredestrant: Investigational estrogen receptor degrader targeting ESR1 mutations.
• Immunotherapy: Trials combining PD-1 inhibitors with chemotherapy are ongoing, though data is still limited.

IV. Symptom Management and Supportive Care

• Bone Metastases:
  • Bisphosphonates (e.g., Zoledronic acid)
  • Denosumab
• Side Effect Management:
  • Addressing hot flashes, osteoporosis (Calcium, Vitamin D, Zoledronic acid), dyslipidemia
  • CDK4/6 inhibitors may cause neutropenia and fatigue, requiring blood count monitoring

V. Considerations for Special Populations

Menopausal Status Assessment

• Premenopausal: Regular menses, low FSH
• Postmenopausal: Amenorrhea ≥12 months, high FSH

Pregnancy-Associated Breast Cancer

• Tamoxifen and AIs are contraindicated in pregnancy
• Treatment can resume postpartum

Genetic Testing

• PIK3CA, ESR1, BRCA1/2 mutations should be assessed to guide targeted therapy

Surveillance and Monitoring

• Routine follow-ups with breast ultrasound, CT scan, bone scan to track metastasis and recurrence

VI. Cutting-Edge Innovations in 2025

1. Expanded Use of CDK4/6 Inhibitors

• Approved for adjuvant therapy in high-risk early breast cancer (e.g., Abemaciclib)

2. Epigenetic Therapy

• HDAC inhibitors in clinical trials combined with endocrine therapy

3. Personalized Medicine

• Liquid biopsy (ctDNA) used to monitor dynamic tumor mutations for real-time treatment adjustment

VII. Cellular Therapy Breakthrough: CAR-T for Solid Tumors

BZD1901: CAR-T Therapy for Mesothelin-Positive Breast Cancer

What is BZD1901?

• The first CAR-T therapy engineered to release its own PD-1 nanobody, enhancing persistence and antitumor activity.
• Targets mesothelin, a surface antigen expressed in ~50% of breast cancers, as well as other solid tumors.

Key Clinical Trial Outcomes:

• Conducted under Good Clinical Practice (GCP) standards
• 100% Disease Control Rate (DCR) in malignant mesothelioma
• 63.6% Objective Response Rate (ORR) including:
  • 1 Complete Response (CR) maintained for 24 months
  • 6 Partial Responses (PR)
• No severe adverse events reported, indicating excellent safety

Scientific Significance

• Mesothelin is widely expressed in cancers such as:
  • Lung
  • Gastric
  • Ovarian
  • Pancreatic
  • Breast
• PD-1 nanobody helps overcome tumor immune evasion and improves CAR-T cell functionality in the tumor microenvironment

Implications for Breast Cancer

• Offers a promising solution to challenges in solid tumor immunotherapy, such as poor T-cell infiltration and immunosuppressive environments
• Particularly valuable for triple-negative breast cancer (TNBC) with mesothelin expression

VIII. The Future: BZD1901 and Beyond

• Further trials aim to test BZD1901 in broader tumor types and explore combinations with checkpoint inhibitors and chemotherapy
• Part of the Bai Ze Plan, targeting 60% accessibility of advanced cellular therapies in the next decade
• Aligned with global precision oncology goals to boost survival and reduce the burden of metastatic breast cancer

Conclusion

The landscape of advanced breast cancer treatment in 2025 is marked by groundbreaking innovations—from CDK4/6 inhibitors and personalized endocrine therapy regimens to next-generation CAR T-cell therapies like BZD1901. These advancements represent not just therapeutic progress but a shift toward personalized, hope-driven oncology care.

Patients and healthcare providers now have more options than ever to manage and even potentially overcome one of the world’s most challenging cancers.

By Dr. Nishant Mittal, PhD
Published: June 22, 2025