What are the treatment options for stage 4 (metastatic) breast cancer?

From the Guidelines

Treatment for stage 4 breast cancer should prioritize systemic therapies to control cancer growth, with the goal of prolonging survival while maintaining quality of life, as stage 4 breast cancer is generally considered incurable but often manageable as a chronic condition for extended periods. The treatment approach depends on several factors including hormone receptor status, HER2 status, location and extent of metastases, previous treatments, and the patient's overall health.

Key Considerations

• Hormone receptor-positive breast cancers may be treated with endocrine therapies such as tamoxifen, aromatase inhibitors (letrozole, anastrozole, exemestane), or fulvestrant, often combined with CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) 1.
• For HER2-positive cancers, anti-HER2 therapies like trastuzumab, pertuzumab, T-DM1, or tucatinib are typically used, with pertuzumab plus trastuzumab in combination with a taxane being a preferred option for first-line treatment 1.
• Triple-negative breast cancers often require chemotherapy, with options including taxanes (paclitaxel, docetaxel), anthracyclines (doxorubicin), capecitabine, eribulin, or platinum agents, and immunotherapy with pembrolizumab may be added for PD-L1 positive triple-negative disease 1.
• Local treatments such as surgery or radiation therapy may be used to address specific symptoms or complications, and supportive care, including pain management and bone-strengthening medications like bisphosphonates or denosumab, is also essential 1.

Treatment Options

• The NCCN panel recommends pertuzumab plus trastuzumab in combination with a taxane as a preferred option for first-line treatment of patients with HER2-positive metastatic breast cancer 1.
• For patients with triple-negative breast cancer, combination chemotherapy regimens containing a platinum agent or a taxane have been shown to be efficacious, with albumin-bound paclitaxel plus carboplatin being a recommended option 1.
• The NCCN panel has classified chemotherapy agents into 3 categories: “preferred,” “other recommended,” and “useful in certain circumstances,” with taxanes, anthracyclines, antimetabolites, microtubule inhibitors, and platinum agents being preferred single agents for patients with metastatic breast cancer 1.

From the FDA Drug Label

Table 11 H0648g: Efficacy Results inFirst-Line Treatment for Metastatic Breast Cancer Combined ResultsPaclitaxel SubgroupACa Subgroup trastuzumab + All Chemo- therapy (n = 235) All Chemo- therapy (n = 234) trastuzumab + Paclitaxel (n = 92) Paclitaxel (n = 96) trastuzumab + ACa (n = 143) ACa (n = 138) Time to Disease Progression (TTP) Median (months)b,c 7.2 4.5 6.7 2.5 7.6 5.7 95% CI 7,8 4,5 5,9 5,10 2,4 7,9 5,7 p-valued < 0.0001 < 0.0001 0.002 Overall Response Rate (ORR)b Events (n) 45 29 38 20 55 23 95% CI 39,51 23,35 28,48 9,22 42,67 8,24 p-valuee < 0.001 < 0.001 0.10 Duration of Response (DoR) Median (months)b,c 8.3 5.8 8.3 4.3 8.4 6.4 25%, 75% Quartile 6,15 4,8 5,11 4,8 6,15 4,9 Overall Survival (OS) Median (months)c 25.1 20.3 22.1 18.4 26.8 21.4 95% CI 22,30 17,24 17,29 13,24 23,33 18,27 p-valued 0.050 0.170 0.16

Stage 4 breast cancer treatment with trastuzumab and paclitaxel may be effective, as shown in the efficacy results of the H0648g study.

• The median time to disease progression was 7.2 months for patients receiving trastuzumab and chemotherapy, compared to 4.5 months for those receiving chemotherapy alone.
• The overall response rate was 45% for patients receiving trastuzumab and chemotherapy, compared to 29% for those receiving chemotherapy alone.
• The median duration of response was 8.3 months for patients receiving trastuzumab and chemotherapy, compared to 5.8 months for those receiving chemotherapy alone.
• The median overall survival was 25.1 months for patients receiving trastuzumab and chemotherapy, compared to 20.3 months for those receiving chemotherapy alone 2. Paclitaxel dosing for breast cancer is recommended at 175 mg/m2 administered intravenously over 3 hours every 3 weeks 3.

From the Research

Stage 4 Breast Cancer Treatment Options

• Systemic therapy is the cornerstone of treatment for stage IV breast cancer, with surgery and radiation therapy also playing a role in certain cases 4, 5
• The addition of surgery to systemic therapy has been shown to improve overall survival in patients with stage IV breast cancer, particularly those with hormone receptor-positive and HER2-positive disease 4, 5
• Neoadjuvant chemotherapy, which involves administering chemotherapy before surgery, has been shown to improve survival outcomes in patients with stage IV breast cancer 4, 6

Treatment Considerations by Tumor Subtype

• For patients with HER2-positive stage IV breast cancer, treatment with trastuzumab and pertuzumab in combination with chemotherapy has been shown to improve overall survival and progression-free survival 7, 6
• For patients with hormone receptor-positive and HER2-negative stage IV breast cancer, endocrine therapy is the mainstay of treatment, with combinations of cyclin-dependent kinase 4/6 inhibitors and chemotherapy also being used 8
• For patients with triple-negative stage IV breast cancer, chemotherapy is the primary treatment option, although new therapies such as antibody-drug conjugates are being developed 8

Factors Influencing Treatment Outcomes

• The timing of surgery and the efficacy of systemic therapy have been shown to influence treatment outcomes in patients with stage IV breast cancer 5
• The sequence of chemotherapy in relation to surgery is also significant, with neoadjuvant chemotherapy being associated with improved survival outcomes in certain cases 4, 6