Metastatic breast cancer

What is tumor seeding in metastatic breast cancer?

Metastatic breast cancer (MBC) occurs when tumor cells from the primary site move through the body and seed or implant in another location in your body. According to recent studies, 6% of breast cancer patients may have metastatic lesions and not even know it. Of women diagnosed with primary breast cancer, between 12% to 30% will develop metastasis in their lifetime.

The mechanisms and routes of metastasis vary and are known as tumor seeding. Understanding the specific type of tumor seeding in your clinical diagnosis guides your provider and treatment plan. Most tumor seeding occurs as part of the metastatic process; however, some procedures are also associated with seeding.

What is tumor seeding?

Tumor seeding occurs when cells from the tumor slough off and invade the immediate surrounding tissues or are transported throughout the body in the blood or lymph fluid. To fully invade the area, the following conditions must exist:

The tumor cells break away from the primary or site of origin. This can be through the sloughing of tumor cells or invasive DNA proteins exiting the cancer cell and implanting in a healthy cell.
Tumor cells must have a route of travel throughout the body. These routes consist of local invasion, displacement of tumor cells during a procedure, invasion of the blood, invasion of the lymphatic system, or invasion of the endocrine system, where hormones and other body chemicals can activate tumor cell growth.
Once the cancer cells reach the new location, known as the tumor microenvironment (TME), they must attach to healthy cells and avoid the body’s immune system. Tumor seeding is opportunistic and occurs more frequently in patients who are immunocompromised.

What are the mechanisms of tumor seeding?

There are four primary mechanisms of tumor seeding:

Local invasion: This occurs in three different ways:
Pressure from the tumor on surrounding structures allows the cancer cells to invade.
Sloughing enzymes and DNA called tumor markers invade healthy cells and cause cancerous mutations.
The tumor grows directly into another organ or tissue touching the primary tumor.
Intravasation: The cancer cells use enzymes to break down the membranes of the blood or lymph vessels and enter the circulatory system. The cells travel throughout the body to all organs and tissues. Once a suitable TME is found for the cancer cells, they will invade the area and grow as a secondary tumor.
Extravasation: When in circulation, the cancer cells invade the blood vessel walls and spill into the surrounding tissues. Once seeded, the cancer cells grow into a secondary tumor.
Angiogenesis: As tumors grow, they require a supplemental blood supply, and angiogenesis creates new localized blood vessels to feed the cancer. This causes the healthy cells in the area to starve for blood and oxygen, allowing the tumor to take over the area.

Cancer cells can also travel back to the primary tumor site and feed the primary tumor, causing rapid growth. This is a process known as tumor self-seeding. Tumor seeding and the resulting metastasis are the primary indicators of mortality in breast cancer patients, decreasing the five-year survival rate to 37% in patients with distant secondary tumors.

What factors contribute to tumor seeding?

Factors contributing to tumor seeding include the tumor microenvironment (TME), the extracellular matrix (ECM) and basement membranes (BM) of local structures, tumor cell adhesion factors, and tumor cell mechanical displacement.

TME: Local healthy cell types, immune system cells, and cancer fibroblasts or growth cells make up the environment suitable for tumor growth and invasion. The new cells in the region have weak ECMs or BMs, allowing the cancer cell's DNA to take over. If the TME is suitable for tumor cell growth, local invasion, intravasation, and extravasation begin.
Adhesion factors: Tumor cells with low or absent adhesion factors allow the cells to break off or slough from the primary tumor and travel through the body, searching for a suitable TME for metastatic growth.
Tumor cell mechanical displacement: In rare cases, the displacement of tumor cells collected during a biopsy or surgical procedure can introduce the cancer cells into local structures, the bloodstream, or the lymphatic system. Core needle or vacuum-assisted biopsy procedures pull tumor cells out of the site and drag them through healthy tissue. In some cases, this causes the cancer cells to invade the area and give rise to a secondary tumor. Metastatic tumor growth due to mechanical displacement is rare and occurs in approximately 3% to 4% of patients.

Tumor seeding prevention strategies.

Supporting your body’s immune system through nutrition, hydration, and lifestyle changes may help your quality of life when dealing with tumor seeding. When the immune system is healthy, killer cells destroy cancer cells and prevent metastasis.

Nutrition: A diet high in fruits and vegetables, whole grain carbohydrates, and healthy fats support the immune system. While these foods do not kill cancer cells, they bolster your immune system, improving your natural defense mechanisms.
Hydration: Water is the primary hydration liquid your body needs. Other liquids are also helpful, but avoid processed foods, sugar and artificial sweeteners, fad diets, or extreme diets as they can tax the body and further dehydrate you.
Dietary supplements: Vitamin C, probiotics, certain amino acids, and sleep-supportive herbs are some of the building blocks of a healthy immune system. Take as advised by your provider.

New techniques include using a chemotherapeutic medication, doxorubicin, to prevent tumor seeding. The development of gelatin-doxorubicin sticks (GDSs) for tumor implantation during core needle biopsies shows promise in preventing tumor seeding secondary to mechanical displacement. During the procedure, the biopsy needle is soaked in doxorubicin, and the GDS is inserted into the lumen of the needle and implanted in the tumor. Because the chemotherapy delivery system is gelatin, the stick dissolves slowly in the tumor, killing cancer cells while dragging them out through aspiration. These studies are in the early phases and are not yet available for human use.

If you or a loved one has metastatic breast cancer, there is help available. Join the Inspire Communities for Breast Cancer, Advanced Breast Cancer, Women and Cancer, and the Cancer Immunotherapy Community for support.

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Disclaimer

Member comments have been lightly edited for length and clarity. This content is for general informational purposes only and does not necessarily reflect the views and opinions of any organization or individual. The content should not be used as a substitute for professional medical advice, diagnosis, or treatment. Please consult your healthcare provider about any questions you may have regarding a medical condition.

Written by: Becky E. Zook RN, BSN, MS

Published on 4/16/24

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