Metastatic Breast Cancer: Symptoms, Treatment & Prognosis

Doctor explaining to a patient the result of her mammogram.

By Kevin FamuyiroSenior Content Strategist

March 13, 2025 12:08 PM PT

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Metastatic breast cancer (MBC) or stage IV breast cancer is when cancer spreads beyond the breast and regional lymph nodes to distant sites like bones, liver, lungs or brain. Breast cancer cells travel through the blood stream and establish new tumors in various organs. This stage of breast cancer is a big clinical challenge as it’s not curable in most cases. But with systemic therapy, targeted therapies and personalized treatment, many patients are living longer and better.

Despite all these advances, metastatic breast cancer still accounts for a big chunk of cancer morbidity and mortality worldwide. This article will go into the epidemiology, prognosis, metastatic patterns, treatment options and emerging trends, so clinicians can apply to patient care.

Table of Contents

Epidemiology and Prognosis
Patterns of Metastasis and Survival
Symptoms and Diagnosis
Treatment
Emerging Data and New Therapies
Patient Care: Psychosocial Considerations
Closing Thoughts
References

Epidemiology and Prognosis

Globally, metastatic breast cancer diagnosed at initial presentation is 6-10% in high income countries. Over 685,000 women worldwide live with metastatic breast cancer, that’s the burden of the disease and the growing number of patients who are living longer due to better treatments. But this percentage is higher in low and middle income countries because of delayed diagnosis and limited access to healthcare. Screening and early detection have reduced stage IV diagnosis in developed countries but metastatic recurrence is common even after treatment of earlier stage disease.

Prognosis

Prognosis for metastatic breast cancer is variable depending on factors like tumor subtype, metastatic site, response to treatment and extent of cancer growth:

70-80% of patients will die from the disease within 5 years of diagnosis. But survival rates vary greatly depending on tumor subtype. For example, patients with HER2 positive metastatic breast cancer do better because of HER2 targeted therapies and some patients can live more than 10 years. Patients with triple negative breast cancer (TNBC) have a more aggressive clinical course and shorter survival as there are limited treatment options outside of chemotherapy and immunotherapy.
But a subset of patients, especially those with specific biomarker profiles can live more than 10 years. For example, patients with HER2 positive disease have benefited a lot from HER2 targeted therapies.

Breast Cancer Progression

Breast cancer progression is when cancer cells break away from the primary tumor or nearby lymph nodes and enter the bloodstream or lymphatic system. These rogue cells can travel to other parts of the body and establish new tumors. This process is called metastasis and can happen at any stage of breast cancer but is more common in advanced stages. Understanding how cancer cells disseminate is key to developing treatment strategies and improving patient outcomes.

Patterns of Metastasis and Survival

The pattern of metastatic spread in secondary breast cancer affects prognosis and treatment decisions. Common sites are:

Bone Metastases: Most common, 37.5-39.8% of cases. Imaging modalities like positron emission tomography (PET), magnetic resonance imaging (MRI) and bone scans are used to detect and characterize bone metastases. PET scans are very sensitive in detecting active metabolic lesions while MRI provides detailed visualization of bone marrow involvement. Bone only metastases means more indolent disease.
Visceral Metastases: Involvement of liver, lungs or other organs is seen in 21.9% of patients. These metastases means more aggressive disease.
Brain Metastases: Less common but more morbid site of spread, poor survival.
Multiple Metastases: 33% of patients present with multiple sites of disease.

Survival by Metastatic Site

Bone Metastases: OS is around 38 months, best prognosis among metastatic sites.
Visceral Metastases: OS is around 21 months.
Brain Metastases: Patients with brain metastases have the worst outcomes, median survival less than 12 months even with aggressive treatment.

Recognizing secondary breast cancer symptoms is important as symptoms can vary depending on the metastatic site and will lead to further testing and evaluation by healthcare professionals.

Symptoms and Diagnosis

Symptoms of metastatic breast cancer can vary greatly depending on where the cancer has spread. Common symptoms are:

Bone pain or tenderness: Means cancer has spread to the bones.
Fatigue or weakness: Feeling tired that doesn’t go away with rest.
Weight loss or loss of appetite: Unintended weight loss or decrease in appetite.
Nausea or vomiting: Caused by cancer spreading to the liver or other organs.
Difficulty breathing: Lung involvement.
Coughing or wheezing: Persistent cough or wheezing means lung metastasis.
Abdominal pain or swelling: Liver or abdominal metastasis.
Headaches or seizures: Neurological symptoms if cancer has spread to the brain.

If you experience any of these symptoms, see a doctor immediately. Early detection and treatment of metastatic breast cancer can improve prognosis and quality of life.

Treatment

Systemic Therapy

Systemic therapy is the main stay of management for metastatic breast cancer patients. Treatment is tailored to the tumor biology, hormone receptor status, HER2 expression and genetic markers like BRCA mutations.

Hormone Therapy

For ER+ HER2- disease.
Agents include aromatase inhibitors, SERMs and SERDs.
CDK4/6 inhibitors like palbociclib have improved outcomes when combined with hormone therapy. ^[³^] However, resistance mechanisms like alterations in RB1 pathway, upregulation of cyclin E1 and activation of alternative pathways (e.g. PI3K/AKT/mTOR) can limit their long term efficacy. Emerging approaches to overcome resistance include combining CDK4/6 inhibitors with targeted agents like PI3K or mTOR inhibitors and next generation CDK inhibitors with broader activity. Ongoing trials are looking to define optimal sequencing to delay resistance and improve outcomes. ^[⁷^]

Targeted Therapy

HER2 targeted therapies (e.g. trastuzumab, pertuzumab, trastuzumab deruxtecan) have changed the landscape for HER2+ metastatic breast cancer and some patients can achieve long term remission. ^[⁹^]
PARP inhibitors for BRCA mutated cancers. ^[5^]
Newer agents like PI3K inhibitors (e.g. alpelisib) target specific genetic alterations. ^[⁸^]

Chemotherapy

Chemotherapy is the mainstay for triple negative breast cancer (TNBC) and visceral crisis.
Agents like sacituzumab govitecan have shown activity in heavily pretreated TNBC.

Local Therapy

While systemic therapy is first line, local therapy can provide palliation or address oligometastatic disease:

Surgery: Metastasectomy may be considered for isolated metastases in the liver or lungs. Note the SABR-COMET trial showed that stereotactic ablative radiotherapy (SABR) can improve overall survival in oligometastatic disease including breast cancer. ^[²^] The MF07-01 trial also showed a survival benefit for patients who underwent locoregional surgery in de novo metastatic breast cancer. These trials suggest aggressive local therapy may be useful in selected patients but more trials are needed to confirm and define patient selection. ^[¹^]
Radiation Therapy: For symptom control of pain or spinal cord compression from bone metastases.
Locoregional Therapy: Treatment of the primary breast tumor in de novo metastatic disease is controversial but may provide local symptom relief.

Oligometastatic Disease

Oligometastatic disease is defined as limited metastatic burden, typically less than 5 sites. Survival outcomes for oligometastatic disease patients can vary greatly depending on the extent of treatment. For example the SABR-COMET trial showed a 13 month improvement in overall survival when stereotactic body radiotherapy (SBRT) was added to standard care, so there is potential for durable disease control in select patients. These studies emphasize the importance of precise imaging and multidisciplinary evaluation to identify patients for aggressive therapy. Precise imaging is key in metastatic breast cancer to identify patients for aggressive therapy. Aggressive approaches including surgery and stereotactic body radiotherapy (SBRT) have been explored to achieve durable control. But more trials are needed to confirm the benefit of these strategies.

Emerging Data and New Therapies

Early data suggests breast reconstruction in de novo metastatic disease patients may be associated with longer survival. But more data is needed to account for potential biases (healthier patients are more likely to get reconstructed).

Systemic therapies:

Antibody-drug conjugates (ADCs) trastuzumab deruxtecan
Immune checkpoint inhibitors: Pembrolizumab in PD-L1 positive TNBC ^[⁴^]
New targets: Agents against Trop-2 and other emerging biomarkers.

Biomarker Driven Therapies for Breast Cancer Cells

Next generation sequencing (NGS) allows clinicians to identify actionable mutations and get patients into clinical trials of targeted therapy. Personalized medicine is becoming increasingly important in metastatic breast cancer management. ^[⁶^]

Patient Care: Psychosocial Considerations

Living with metastatic breast cancer is mentally and emotionally challenging for patients. Common issues:

Anxiety and depression related to prognosis.
Financial toxicity from long treatment.
Social isolation and need for support networks.

Interdisciplinary teams including oncology social workers and mental health professionals are key to addressing these issues.

Palliative and End of Life Care

Since metastatic breast cancer is incurable for most patients, palliative care is important for:

Symptom management (e.g. pain, fatigue, dyspnea).
Emotional and spiritual needs.
End of life discussions and advance care planning.

Closing Thoughts

While metastatic breast cancer remains a clinical challenge, treatment and personalized medicine have improved outcomes for many patients. Metastasis is when cancer cells travel to other parts of the body and create tumors. The prognosis of metastatic breast cancer varies based on the site of the tumors. Of the types of metastasis, bone metastasis has the best prognosis, while visceral and brain metastasis have the worst prognosis. The pattern and biology of the tumor, along with personalized medicine, drive the most positive outcomes.

References

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