Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.
It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer.
Breast cancer can metastasize anywhere in body but primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain, with the most common site being the bone. Treatment of metastatic breast cancer depends on location of the metastatic tumours and includes surgery, radiation, chemotherapy, biological, and hormonal therapy.
Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components. Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues. The targeting by cancer cells of specific organs is probably regulated by chemo-attractant factors and adhesion molecules produced by the target organ, along with cell-surface receptors expressed by the tumor cells.
The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:
- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.
- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.
- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting.
- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.
- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.
BC Cancer - Breast Cancer Management Guidelines
6.9 Metastatic Breast Cancer
The introduction of population based screening and adjuvant treatment are important contributors to declining breast cancer mortality rates observed in western countries over the last 4 decades.1 Despite these advances, metastatic breast cancer remains one of the leading causes of cancer related mortality in women. The majority of women with metastatic breast cancer have relapsed after curative-intent therapy for early breast cancer; a smaller proportion present with distant metastases at initial diagnosis. Breast cancer is distinctly uncommon in men, however treatment principles are similar to those described below.
6.9.2 Patterns of Spread
Most patients with metastatic breast cancer have widespread disease, with bone being the commonest site. Lung, liver, and soft tissue (nodes, skin) are also commonly involved. Parenchymal brain metastases are common during the course of metastatic her2+ breast cancer and triple negative (hormone receptor and her2 negative) breast cancers, less so among ER+ cancers. Lobular histology cancers can spread to the ovaries, peritoneal cavity, and pleura.
Metastatic breast cancer is incurable with currently available therapies. The median survival is approximately 24 months. However, there is a wide range of survival, from several months in extreme cases, to 5 or more years. In general, patients with a long interval between early breast cancer diagnosis and metastatic relapse live longer than those with shorter disease free intervals. A small but significant fraction of patients achieves long-term disease control and survives more than 10 years. Survival patterns differ by type of breast cancer: patients with metastatic her2+ or metastatic ER+ cancers survive 4 to 5 years on average, while patients with metastatic ER-/her2- (triple negative cancers) typically survive a year or less.