Understanding breast cancer metastasis

Metastasis is a complex process by which the malignant cancer cells from the breast expand into other regions of the body. Once metastasis has occurred, it is much more difficult to effectively treat breast cancer. If breast cancer has metastasized to other areas of the body, it is termed a ‘stage IV‘ breast cancer. Sometimes metastasis has occurred at the same time the original breast cancer is diagnosed. But in other cases the metastasis of breast cancer is found months or even years after the initial treatment. This would be termed a ‘recurrent‘ breast cancer.

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Breast Cancer cells migrate through the blood vessels or lymphatic channels

Breast cancer cells will typically travel wither through the lymphatic system or through blood vessels to reach distant areas of the body. When breast cancer metastasize to the axillary lymph nodes (under the arm) it is still considered to be a relatively early stage of metastasis, and is potentially curable. But once the breast cancer moves beyond the lymph nodes into other areas of the body, it is usually termed a ‘distant‘ metastasis, and a patient is unfortunately usually not curable at that point.

Metastatic breast cancer is called ‘systemic’

If breast cancer has metastasized beyond the lymph nodes it is termed a ‘systemic‘ disease. That means that the ‘whole body‘ must be treated and not just a particular spot. The only way to effectively treat the whole body is through chemotherapy and hormonal therapy.

Breast cancer metastasizes primarily to the bone, lungs, and brain

Breast cancer tends to metastasize primarily to the lungs, liver, brain, and regional lymph nodes, and the bone. About 70% of breast cancer deaths are due to breast cancer metastasis to the bone, with the next most common site of breast cancer metastasis is the brain, at close to 10%.

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Mechanisms of breast cancer metastasis: current research

No one really knows what factors will make a certain patient more or less susceptible to breast cancer metastasis. There is growing awareness that part of that susceptibility is due to the ‘host factors‘; characteristics of the non-malignant cells and the general biological environment surrounding the malignant breast tumor. Sometimes this is referred to as the ‘pre-metastatic niche‘, and it is thought that bone-marrow-derived progenitor cells may directly influence the dissemination of malignant cells to distant areas. Non-neoplastichost cells‘ within the tumor may also play a key role in the regulation of breast cancer metastasis.

Regulatory T-cells and RANKL proteins may play a role in breast cancer metastasis

Recent breast cancer research suggest that the body’s regulatory T cells, which are an integral part of the immune-response system, may play a key role in metastasis. It is speculated that the T cells produce a protein which seems to accelerate the spread of breast cancer cells to other areas of the body. The inflammatory protein RANKL seems to influence the T-cells’ ability to spread cancer cells to distant areas of the body. It is believed that by interfering with RANKL’s ability to interact with the T-cells, the early metastasis of breast cancer cells can be significantly inhibited.

Statistically, 20% to 40% of all breast cancers will metastasize at some point

According to some estimates, between 20% to 30% of all women first diagnosed with localized breast cancer will usually develop it in other areas of the body. In about 10% of original breast cancer diagnoses metastasizes has already occurred. Following breast cancer treatment, it has been estimated that up to 40% of women will experience a relapse and develop a distant metastasis. In the United States in 2011 there are an estimated 16200 women living with metastatic breast cancer.

Breast cancer metastasis may occur more than 10 years after the original treatment

Some estimates suggest that between 10% to 15% of all diagnoses will be of aggressive forms of the breast cancer which will potentially metastasize within three years following the original diagnosis. However, breast cancer metastasis can take place 10 years or even longer after the original treatment. Metastasized or potentially metastatic breast cancer treatment usually takes the form of adjuvant chemotherapy (also called ‘systemic‘ therapy).

While the choice to undergo chemotherapy will always be determined on an individual basis, the fact remains that approximately 80% of all breast cancer patients are treated with some degree of adjuvant chemotherapy. Statistically, the use of adjuvant chemotherapy to treat and prevent the spread of metastatic breast cancer can lead to a 3% to 10% increase in the 15 year breast cancer survival rate overall.

Statistics for metastatic breast cancer are not favorable, but each case will be unique

It is important to be realistic about survival of metastatic breast cancer. Approximately 90% of deaths due to breast cancer are from metastasis, and the overall survival rate for metastasized breast cancer is only about 16%. Still, almost 20% of women with metastatic breast cancer may still live more than five years. Above all one should remember that the situation for each woman will be unique, and ultimately statistics are meaningless. No one can predict with any degree of certainty whether or not the body will either experience or be able to recover from metastatic breast cancer.


For further reading, I suggest you visit this page on Breast Cancer Treatment.
Below is a little quiz regarding Breast Cancer Metastasis…:

  • Can any type of cancer form a metastatic tumor? Virtually all cancers, including the cancers of the blood and the lymphatic system can form metastatic tumors. Although rare, the metastasis of blood and lymphatic system cancers to the lung, heart, central nervous system, and other tissues have been reported.
  • Where does the cancer spread to? The most common sites of cancer metastasis are to the bone, liver and the lung. Although most cancers have the ability to spread to many different parts of the body, they usually spread to one site more often than others.
  • How does cancer spread? Cancer cell metastasis usually involves the following steps: local invasion, intravasation, circulation, arrest and extravasation, proliferation, and angiogenesis. Because cancers to the lymphatic system or the blood system are already present inside lymph vessels, lymph nodes, or blood vessels not all of these steps are needed for their metastasis. Also, the lymphatic system drains into the blood system at two locations on the neck. The ability of a cancer cell to metastasize successfully depends on it’s individual properties.
  • Does metastatic breast cancer have any symptoms? The symptoms produced by metastatic breast cancer vary by the location of the metastases. For example, 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 persistent, progressively worsening headache, visual changes, seizures, nausea, 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. And other non specific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss and poor appetite.
  • Can someone have a metastatic tumor without having primary cancer? No. A metastatic tumor is always caused by cancer cells from another part of the body.
  • If a person who was previously treated for cancer gets diagnosed with cancer a second time, is the new cancer a new primary cancer or metastatic cancer? The cancer may be a primary cancer, but, in most cases, it is metastatic cancer.
  • What treatments are used for metastatic cancer? Metastatic cancer may be treated with chemotherapy, biological therapy, targeted therapy, hormonal therapy, radiation therapy, surgery, or a combination of these treatments. The choice of treatment generally depends on the type of primary cancer; the size, location, and the number of metastatic tumors; the patient’s age and general health; and the types of treatment the patient has had in the past.
  • Are new treatments for metastatic cancer being developed? Yes. Researchers are now studying new ways to kill or stop the growth of primary cancer cells and metastatic cancer cells, including new ways to boost the strength of immune responses against tumors.

References

  1. Costelloe, C. M.; Rohren, E. M.; Madewell, J. E.; Hamaoka, T.; Theriault, R. L.; Yu, T. K.; Lewis, V. O.; Ma, J. et al. (2009). Imaging bone metastases in breast cancer: Techniques and recommendations for diagnosis. The Lancet Oncology 10 (6): 606–614
  2. Elston CW, Ellis IO. Pathologic prognostic factors in breast cancer. I. The value of histological grades in breast cancer. Experience from a large study with long-term follow-up. Histopathology (1991), 19:403-410.
  3. Tan, W., Zhang, W., Stranser, A., Grivennivov, S., Chen, JQ., Hoffman, RM., Karin, M. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL–RANK signalling. Nature, 2011
  4. Talmadge JE, Fidler IJ. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. (July 2010)70(14):5649-69.
  5. Disibio G, French SW. Metastatic patterns of cancers: results from a large autopsy study. Arch Pathol Lab Med. (Jun 2008) 132(6):931-9.
  6. Coghlin C, Murray GI. Current and emerging concepts in tumour metastasis. J Pathol. (Spet. 2010) 222(1):1-15.
  7. Kreisman H,Wolkove N,Finkelstein HS, et al. Breast cancer and thoracic metastases: review of 119 patients. Thorax. (1983);38:175–179.
  8. Vollmer, RT.,Primary Lung Cancer vs Metastatic Breast Cancer: A Probabilistic Approach. Am J Clin Pathol (2009) 132:391-395

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