The pathophysiology of breast cancer involves understanding the functional changes that occur within the body due to this disease. Breast cancer is characterized by the uncontrolled growth of cells originating in the breast tissue. This article will explore the biological mechanisms governing how breast cancer develops and progresses within the body.
The Cellular Origins of Breast Cancer
Normal cells in breast tissue follow a regulated cycle of growth, division, and programmed death, known as apoptosis. This precise cellular choreography ensures tissue maintenance and repair. However, in breast cancer, this intricate process becomes disrupted, leading to unchecked cell proliferation and a failure of abnormal cells to undergo self-destruction.
The root of this disruption often lies in genetic mutations, which are alterations in a cell’s DNA. These mutations can be inherited from parents, known as germline mutations, or acquired during a person’s lifetime due to environmental factors or errors in DNA replication. Such genetic changes affect two main categories of genes that regulate cell growth.
One category includes oncogenes, which, when mutated, act like an accelerator, constantly promoting cell division and growth. The other comprises tumor suppressor genes, which normally function like brakes to halt uncontrolled cell growth and initiate DNA repair or cell death. When these tumor suppressor genes acquire harmful mutations, their braking function is lost, allowing abnormal cells to multiply without restraint.
Prominent examples of tumor suppressor genes linked to breast cancer are BRCA1 and BRCA2. When these genes are mutated, they significantly increase a person’s susceptibility to developing breast and ovarian cancers because their ability to repair damaged DNA is compromised. While hereditary factors account for a smaller percentage, approximately 5% to 10%, of all breast cancer cases, these mutations can lead to cancer development at younger ages.
Hormonal Influence on Tumor Growth
Beyond genetic alterations, certain hormones play a significant role in fueling the growth of many breast cancers. Some breast cancer cells possess specific proteins on their surface called estrogen receptors (ER) and progesterone receptors (PR). These receptors act as binding sites for the body’s natural hormones, estrogen and progesterone, which normally regulate breast development and function.
When estrogen or progesterone hormones bind to these receptors on cancer cells, they send signals that stimulate the cell to grow and divide. This interaction essentially provides the “fuel” necessary for the cancer to proliferate. Approximately 60% to 70% of all breast cancers are estrogen receptor-positive (ER+), meaning they rely on estrogen for growth.
Cancers are classified as hormone receptor-positive (HR+) if they have either estrogen or progesterone receptors, or both. This distinction is important because HR+ cancers can often be treated with therapies that block the effects of these hormones or reduce their levels. In contrast, hormone receptor-negative (HR-) cancers lack these receptors and do not rely on hormonal stimulation for growth, requiring different treatment approaches.
Tumor Progression and Invasion
Once mutated cells proliferate unchecked, they can form a primary tumor. For this tumor to grow, it requires its own dedicated supply of oxygen and nutrients. This demand triggers a crucial process called angiogenesis, where the tumor stimulates the formation of new blood vessels from existing ones within the surrounding tissue.
Tumor cells, along with cells in the surrounding tumor microenvironment, release specific signaling molecules like vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGFs). These molecules promote the proliferation and migration of endothelial cells, which are the cells lining blood vessels, leading to a new, often disorganized, vascular network that feeds the growing tumor. This new blood supply allows the tumor to expand and provides pathways for potential spread.
Breast cancers are categorized based on whether they remain confined to their original location or have invaded surrounding tissues. Ductal carcinoma in situ (DCIS) is a non-invasive form where abnormal cells are contained within milk ducts and have not broken through the duct wall. It is an early-stage cancer, often curable, with a very low risk of metastasis.
In contrast, invasive ductal carcinoma (IDC) is the most common type of invasive breast cancer, accounting for about 80% of all invasive cases. In IDC, cancer cells have broken through duct walls and infiltrated surrounding breast tissue. This invasion into adjacent tissue marks a significant step in the disease’s progression, increasing the potential for the cancer to spread to distant parts of the body.
The Process of Metastasis
Metastasis is the advanced stage of breast cancer, characterized by the spread of cancer cells from the primary tumor in the breast to distant organs or tissues in the body. This process begins with cancer cells breaking away from the primary tumor site.
Following local invasion, these detached cancer cells enter nearby lymphatic or blood vessels, a step known as intravasation. Once inside the circulatory or lymphatic system, they travel through the body. While circulating, many cells perish, but some survive.
Upon reaching a new, distant location, surviving cancer cells exit the vessel, a process called extravasation. The cells then adapt to the new tissue and multiply, forming a secondary tumor. This cascade is an inefficient process, meaning only a small fraction of cells that break away successfully form new tumors.
Breast cancer commonly metastasizes to specific organs. The most frequent sites for secondary tumors include:
- Bones
- Lungs
- Liver
- Brain
Less common sites include the skin, female reproductive tract, digestive tract, pancreas, kidneys, and eyes. Understanding this spread pattern is important for monitoring and managing the disease in its advanced stages.