From the Guidelines
Stage 4 breast cancer in the US refers to metastatic breast cancer that has spread beyond the breast and nearby lymph nodes to distant organs such as the lungs, liver, bones, or brain, and treatment typically involves systemic therapies rather than focusing on local control, with the goal of palliating symptoms, prolonging survival, and maintaining or improving quality of life, as stated in the NCCN Guidelines 1. The standard approach includes:
- Hormone therapy (such as tamoxifen, aromatase inhibitors, or fulvestrant) for hormone receptor-positive cancers
- Targeted therapies (like trastuzumab, pertuzumab, or T-DM1) for HER2-positive cancers
- Chemotherapy (including taxanes, anthracyclines, capecitabine, or eribulin) for triple-negative or rapidly progressing disease
- CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) are often combined with hormone therapy Treatment is typically continuous until disease progression or unacceptable toxicity, and the choice of therapy should be made after consideration of factors such as tumor biology, patient preferences, and previous therapies, as recommended by the NCCN Guidelines 1. The 5-year survival rate for stage 4 breast cancer is approximately 29%, though this varies based on cancer subtype, patient age, overall health, and response to treatment, as mentioned in the study by 1. While stage 4 breast cancer is generally considered incurable, many patients live for years with good quality of life through sequential lines of therapy, supportive care, and management of symptoms and side effects, as stated in the study by 1. Some key considerations in the treatment of stage 4 breast cancer include:
- The use of bisphosphonates for the treatment of hypercalcemia and clinically evident bone metastases, as recommended by the ESMO clinical practice guidelines 1
- The role of radiation therapy in palliative treatment, including the treatment of bone metastases, brain metastases, and painful or fungating soft tissue masses, as mentioned in the study by 1
- The potential benefits and risks of different treatment options, including the use of single cytotoxic drugs versus combination chemotherapy, and the impact of treatment on quality of life, as discussed in the study by 1.
From the FDA Drug Label
KISQALI is a kinase inhibitor indicated: for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with: an aromatase inhibitor as initial endocrine-based therapy; or fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy
Ogivri is indicated in adults: In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
The characteristics and treatment options for Stage 4 (metastatic) breast cancer in the United States (US) include:
- Hormone Receptor (HR)-positive, HER2-negative metastatic breast cancer can be treated with kinase inhibitors such as ribociclib in combination with aromatase inhibitors or fulvestrant 2
- HER2-overexpressing metastatic breast cancer can be treated with trastuzumab in combination with paclitaxel or as a single agent 3 Key considerations for treatment include:
- Patient selection based on HER2 protein overexpression or HER2 gene amplification 3
- Monitoring for cardiac function, infusion reactions, and pulmonary toxicity 3
- Dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability 2
From the Research
Characteristics of Stage 4 (Metastatic) Breast Cancer
- Stage 4 breast cancer is the most advanced stage of breast cancer, where the cancer has spread to distant parts of the body [ 4 ].
- The characteristics of stage 4 breast cancer include the presence of metastases in organs such as the liver, lungs, and bones [ 4 ].
- Hormone receptor and HER2 status are important factors in determining the treatment options for stage 4 breast cancer [ 4 ].
Treatment Options for Stage 4 (Metastatic) Breast Cancer
- Systemic therapy is the cornerstone of treatment for stage 4 breast cancer, with surgery and radiation therapy playing a secondary role [ 4 ].
- The treatment options for stage 4 breast cancer include:
- Systemic therapy alone (ST)
- Systemic therapy and surgery (ST + Surg)
- Systemic therapy, surgery, and radiation (Trimodality)
- The choice of treatment option depends on the hormone receptor and HER2 status of the patient [ 4 ].
- For patients with HER2-positive and hormone receptor-positive metastatic breast cancer, treatment options include trastuzumab, leuprorelin, letrozole, and palbociclib [ 5 ].
- For patients with hormone receptor-positive and HER2-negative metastatic breast cancer, treatment options include ribociclib, palbociclib, and letrozole [ 6,7,8 ].
Survival Benefits of Treatment Options
- The addition of surgery to systemic therapy has been shown to improve survival outcomes for patients with stage 4 breast cancer [ 4 ].
- The sequence of chemotherapy in relation to surgery is significant, with neoadjuvant chemotherapy (NAC) showing a greater survival advantage compared to adjuvant chemotherapy [ 4 ].
- The combination of palbociclib and letrozole has been shown to improve progression-free survival and overall survival outcomes compared to letrozole alone in patients with hormone receptor-positive and HER2-negative metastatic breast cancer [ 8 ].