Metastasis Breast Cancer Notes

Metastasis Breast Cancer General Biology of Tumors

The biology of tumors is described in certain steps:

1. Aggressive Clonal Proliferation and Angiogenesis: The spread of cancer cells is the development of rapidly proliferating clones of cancer cells. Tumor angiogenesis plays a significant role in metastasis since new vessels formed as part of growing tumors are more vulnerable to invasion because these evolving vessels are in direct contact with cancer cells.

2. Tumor Cell Loosening: Normal cells remain glued to each other due to the presence of cell adhesion molecules, i.e. E-cadherin. In epithelial tumors, the cell adhesion molecules are lost which results in the loosening of cancer cells. There is also a loss of integrins, the transmembrane receptors further favor invasion.

Read And Learn More: Pathology Question And Answers

3. Tumor Cells-ECM Interaction: Loosened cancer cells are now attached to ECM proteins mainly laminin and fibronectin. There is also a loss of integrins, the transmembrane receptors which further favor invasion.

4. Degradation of ECM: Certain enzymes like metalloproteinases bring about the dissolution of ECM then make way for tumor cells through the interstitial matrix, and finally dissolve the basement membrane of the vessel wall.

5. Entry ofTumor Cells into Capillary Lumen: The tumor cells after degenerating the basement membrane are ready to migrate to the lumen of capillaries or venules for which the following mechanisms play a role:

• Autocrine motility factor: This is a cytokine derived from the tumor cells which stimulates receptor-mediated motility of tumor cells.
• Cleavage products of matrix components: These are formed following the degradation of the extracellular matrix and have properties of tumor cell chemotaxis, growth promotion, and angiogenesis in cancer. As malignant cells migrated through breached basement membranes, these cells enter the lumen of lymphatic and capillary channels.

6. Thrombus Formation: The tumor cells protruding in the lumen of the capillary are covered with constituents of circulating blood and form a thrombus. Thrombus provides nourishment to tumor cells and also prevents them from immune attack by circulating host cells.

Normally a large number of tumor cells are released in circulation but they are attacked by host immune cells. A very small proportion of malignant cells in the bloodstream survive to develop metastasis.

7. Extravasation of Tumor Cells: Tumor cells may mechanically block vascular channels and attach to vascular endothelium and then extravasate to extravascular space. In this way, the sequence similar to local invasion is repeated and the basement membrane is exposed.

8. Survival and Growth of Metastatic Deposit: The extravasated malignant cells on lodgment in the right environment grow further under the influence of growth factors produced by host tissues, tumor cells, and by cleavage products of matrix components. The metastatic deposits grow further if the host’s immune defense mechanism fails to eliminate them.

Metastatic deposits may further metastasize to some organs or to other sites by forming emboli.

Metastasis Breast Cancer  Spread of Malignant Tumors

Generally, the spread of malignant tumors is in two ways:

Local Invasion or Direct Spread: The malignant tumors invade via the route of least resistance, though eventually, more cancers recognize no anatomic boundaries. Often, cancers extend through tissue spaces, permeate lymphatics, blood vessels, and perineural spaces, and may penetrate a bone by growing through nutrient foramina. More commonly, the tumors invade thin wall capillaries and veins than thick-walled arteries.

Metastasis or Distant Spread

Metastasis is defined as the spread of a tumor by invasion in such a way that a discontinuous secondary tumor mass is formed at the site of lodgment. Cancers may spread to distant sites by the following pathways:

• Lymphatic spread
• Hematogenous spread
• Spread along body cavities and natural passages.

Metastasis Breast Cancer  – Lymphatic Spread

• Carcinomas metastasize by the lymphatic route. A few sarcomas can also spread by the lymphatic route.
• The involvement of lymph nodes by malignant cells is of two forms, i.e. lymphatic permeation and lymphatic emboli.
• Lymphatic permeation: Walls of lymphatics is invaded by cancer cells and can form a continuous growth in lymphatic channels.
• Lymphatic emboli: Malignant cells can detach to form tumor emboli to carry the lymph to the next draining lymph node. Tumor emboli enter the lymph node and its convex surface is lodged in the subcapsular sinus where it grows. Later on, the whole lymph node is replaced and enlarged by a metastatic tumor.
• At times due to obstruction of lymphatics by tumor cells, the lymph flow is disturbed and tumor cells spread against the flow of the limb leading to retrograde metastasis at unusual sites.
• Generally, regional lymph nodes draining tumors are invariably involved in producing regional metastasis for, for example, Carcinoma breast to axillary lymph node carcinoma thyroid to lateral cervical lymph nodes.
• Virchow’s lymph node is nodal metastasis preferentially to supraclavicular lymph node from cancers of abdominal organs, for example, Cancer stomach, colon, and gallbladder.

Metastasis Breast Cancer  – Hematogenous Spread

• This is a common route for sarcomas but a few carcinomas can also metastasize by this route. The common site for blood-borne metastasis are the lung, breast, thyroid, kidney,
• liver, prostate, and ovary.
• Systemic veins drain blood into the vena cava from the limb, head, and neck, and cancers of these sites metastasize to the lungs.
• Portal veins drain blood from the bowel, spleen, and liver, tumors of these organs frequently have secondaries in the liver.
• Arterial spread of tumors is less because they are thick-walled and have elastic tissue which is resistant to invasion.
• Arterial spread can occur when a tumor cell passes through the pulmonary capillary bed or via pulmonary arterial branches which have thin walls.
• Retrograde spread by blood route can occur at various unusual sites because of retrograde spread after venous obstruction as with lymphatic metastasis.

Spread Along Body Cavities and Natural Passages

• Transcoelomic spread: Certain cancers invade through the serosal wall of the coelomic cavity so that tumor fragments or clusters of tumor cells break off the Peritoneal cavity is involved most often. For example, carcinoma of the stomach seeding to both ovaries, carcinoma of the ovary spread to the entire peritoneal cavity.
• Spread along epithelium-lined surfaces: It is unusual for a malignant tumor to spread through the epithelial-lined surfaces since intact epithelium is resistant to penetration of tumor cells. But exceptionally a malignant tumor can spread through a fallopian tube from the endometrium to the ovaries or vice versa, through bronchus into the alveoli.
• Spread via CSF: Malignant tumors of ependyma and leptomeninges may spread by the release of tumor fragments and tumor cells into CSF, they also lead to metastasis at other sites in CNS.
• Implantation: It is very rare that a tumor spread by implantation, i.e. by surgeon’s scalpel, needle, suture, etc. It can also be not implanted by direct contact, i.e. cancer of the upper lip transferred to the lower lip.