When breast cancer spreads from its original site to the liver, it is known as metastatic HER2-positive breast cancer. The presence of HER2-positive status influences both the disease’s behavior and treatment strategies.
Understanding HER2-Positive Breast Cancer and Its Spread to the Liver
HER2-positive breast cancer involves an overexpression of the human epidermal growth factor receptor 2 (HER2) protein on the surface of cancer cells. When an excess of HER2 receptors is present due to a gene abnormality, breast cells can multiply uncontrollably, leading to tumor formation. Approximately 15% to 20% of breast cancers are classified as HER2-positive, and these tend to be more aggressive and grow faster than other breast cancer types.
The liver is a common site for breast cancer metastasis, ranking as the third most frequent location after bones and lungs. This spread occurs as breast cancer cells enter the bloodstream or lymphatic system and are then carried to the liver, where they can settle and grow. The liver’s extensive blood supply and filtering function make it a susceptible organ for these circulating cancer cells.
When breast cancer spreads to the liver, it is still considered breast cancer, not liver cancer, and is treated with breast cancer therapies. The original breast cancer’s HER2 status continues to guide treatment decisions for the metastatic disease. About half of individuals diagnosed with metastatic breast cancer develop liver metastases.
Identifying Symptoms and Diagnosis
Breast cancer that has spread to the liver may present with various symptoms. Common indicators include pain or discomfort in the abdomen, particularly on the right side under the ribs, which may extend to the right shoulder. Other general symptoms include persistent tiredness, nausea or vomiting, loss of appetite, and unexplained weight loss. A swollen abdomen due to fluid buildup (ascites) and hiccups can also occur.
More specific signs of liver involvement include jaundice (a yellowing of the skin and whites of the eyes) and itchy skin. These symptoms arise when the liver’s function is impacted by cancer cells or if bile ducts become blocked.
To diagnose liver metastasis, doctors employ various imaging tests and procedures. Computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans are frequently used to visualize the liver and detect the presence of tumors.
A liver biopsy is often performed to confirm the diagnosis and verify that the liver tumors originated from breast cancer cells. Blood tests can also provide clues, as they may reveal changes in liver enzyme levels or the presence of tumor markers, which can suggest growing or spreading cancer.
Treatment Options
Treatment for HER2-positive breast cancer that has spread to the liver involves systemic therapies, which work throughout the entire body, along with potential local treatments for liver metastases. The specific approach is personalized, considering factors such as the cancer’s characteristics, prior treatments, overall health, and symptoms. The primary goal of treatment is to control the cancer, manage symptoms, and enhance quality of life.
Targeted therapies for HER2-positive metastatic breast cancer specifically block the HER2 protein that drives cancer cell growth. Trastuzumab (Herceptin) and pertuzumab (Perjeta) are monoclonal antibodies that bind to HER2 receptors, inhibiting cancer cell proliferation. These are often given with chemotherapy, forming a standard first-line regimen for HER2-positive metastatic disease. For instance, pertuzumab combined with trastuzumab and docetaxel has demonstrated improved progression-free and overall survival.
Other targeted therapies include antibody-drug conjugates (ADCs) like ado-trastuzumab emtansine (T-DM1 or Kadcyla) and fam-trastuzumab deruxtecan-nxki (Enhertu). ADCs combine a targeted antibody with a chemotherapy drug for more specific delivery to cancer cells. T-DM1 is approved for patients previously treated with trastuzumab and chemotherapy, while fam-trastuzumab deruxtecan-nxki is used for those who have progressed on at least one prior HER2-targeted therapy.
Tyrosine kinase inhibitors (TKIs) such as lapatinib, neratinib, and tucatinib also play a role in treatment. Tucatinib, when combined with trastuzumab and capecitabine, has shown improvements in progression-free and overall survival, including activity against brain metastases. Margetuximab, a newer anti-HER2 monoclonal antibody, combined with chemotherapy has also shown benefits in pretreated patients.
Chemotherapy is frequently used alongside targeted therapies to destroy or slow down cancer cell growth. Chemotherapy agents work broadly to attack rapidly dividing cells. The choice of chemotherapy agent may depend on prior treatments and the patient’s liver function, as some drugs are metabolized by the liver.
Hormone therapy may be included if the HER2-positive breast cancer also tests positive for hormone receptors (estrogen and/or progesterone receptors). These therapies work by blocking hormones or lowering their levels to prevent cancer cells from growing. This is often a long-term treatment.
Radiation therapy and surgery are considered local treatments. Radiation therapy can deliver high-dose beams to cancerous areas to control tumor growth and manage symptoms. Selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) is an option for liver metastases. Surgery to remove liver metastases may be considered in selected cases. Ablation techniques, using heat or cold, can also destroy cancer cells in the liver.
Managing Life with the Condition
Living with HER2-positive breast cancer that has spread to the liver involves ongoing management. Treatment is often continuous and tailored to the individual’s specific needs and how the cancer responds. Supportive care addresses side effects from treatments and symptoms of the disease, which can include fatigue, nausea, and pain.
Managing symptoms like fatigue involves medical interventions and lifestyle adjustments. Nausea and loss of appetite can be addressed with medication and dietary modifications. Treatments can also alleviate discomfort, hiccups, or a feeling of fullness if the liver is enlarged.
The prognosis for HER2-positive breast cancer with liver metastasis has improved with advancements in targeted therapies. While metastatic breast cancer is considered incurable, treatments can control the disease for extended periods, allowing individuals to live for years with a good quality of life. For instance, HER2-positive, hormone receptor-positive patients with liver metastases have shown longer median overall survival compared to other subtypes.
A multidisciplinary care team, including oncologists, nurses, dietitians, and social workers, plays a role in managing the condition. Emotional support is also important, as living with metastatic cancer can be challenging. While overall survival rates for distant HER2-positive breast cancer are around 46% at five years, individual outcomes vary based on treatment response, overall health, and specific cancer characteristics. Clinical trials also offer opportunities to access new and developing treatments.