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How Does Breast Cancer Metastasis

Myth #: Metastatic Breast Cancer Is A Single Type Of Cancer That Will Be Treated The Same Way For Every Person

Breast Cancer Metastasis, When Can It Happen?

The label metastatic contributes to the myth that it is one kind of breast cancer. But like earlier-stage breast cancers, stage IV cancers can have different characteristics that will guide treatment choices. They can test positive or negative for hormone receptors and/or an abnormal HER2 gene the gene that causes the cells to make too many copies of HER2 proteins that can fuel cancer growth. These test results guide treatment choices.

For triple-negative stage IV cancers meaning they test negative for hormone receptors and an abnormal HER2 gene testing for PD-L1 is becoming more common. PD-L1 is a checkpoint protein found on the surface of healthy cells that prevents the bodys immune system T-cells from attacking them. Some breast cancer cells also have large amounts of PD-L1 on their surfaces, which helps shield them from the bodys immune response. Newer immunotherapies are being used to treat PD-L1-positive MBC.

Furthermore, treatment choices can depend on a persons age, overall health, and whether there are other medical conditions present.

The bottom line? Treatments vary. DivineMrsM of Ohio says it well: There is the misconception that there is one standardized treatment for every case of MBC, like a one size fits all. But there are different approaches and it cant always be said that one approach is better than another. Most people dont realize different subcategories of this disease.

What Is Stage Ii Breast Cancer

Stage II describes cancer that is in a limited region of the breast but has grown larger. It reflects how many lymph nodes may contain cancer cells. This stage is divided into two subcategories.

Stage IIA is based on one of the following:

  • Either there is no tumor in the breast or there is a breast tumor up to 20 millimeters , plus cancer has spread to the lymph nodes under the arm.
  • A tumor of 20 to 50 millimeters is present in the breast, but cancer has not spread to the lymph nodes.

Stage IIB is based on one of these criteria:

  • A tumor of 20 to 50 millimeters is present in the breast, along with cancer that has spread to between one and three nearby lymph nodes.
  • A tumor in the breast is larger than 50 millimeters, but cancer has not spread to any lymph nodes.

Looking For More Of An Introduction

If you would like more of an introduction, explore these related items. Please note that these links will take you to other sections on Cancer.Net:

  • ASCO AnswersFact Sheet: Read a 1-page fact sheet that offers an introduction to metastatic breast cancer. This free fact sheet is available as a PDF, so it is easy to print.
  • ASCO AnswersGuide:Get this free 52-page booklet that helps you better understand breast cancer. The booklet is available as a PDF, so it is easy to print.
  • Cancer.Net Patient Education Video: View a short video led by an ASCO expert in metastatic breast cancer that provides basic information and areas of research.

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Regulatory Factors Of The Rankl Pathway

RANKL clearly holds the key to the osteolytic process. In fact, a new drug, denosumab , a fully human monoclonal antibody to RANKL, has been approved by the US Food and Drug Administration for the treatment of postmenopausal women with high risk of osteoporotic fractures, and is under priority review for patients with bone metastases. Osteoblasts and bone stromal cells can respond to a variety of substances that upregulate RANKL. PTH/PTHrP, TNF-, prostaglandins , IL-1, IL-11, FGF-2, and IGF-1 have been reported to increase RANKL production. Cells of the immune system, T cells and dendritic cells can also express RANKL. In this context, RANKL increases in the presence of inflammatory agents from infectious organisms, such as lipopolysaccharide, CpGpDNA and viral double-stranded DNA . Several of these RANKL inducers merit further discussion with respect to metastatic breast cancer-induced osteolysis.

Local Or Regional Treatments For Stage Iv Breast Cancer

Cancers Spread to Bone

Although systemic drugs are the main treatment for stage IV breast cancer, local and regional treatments such as surgery, radiation therapy, or regional chemotherapy are sometimes used as well. These can help treat breast cancer in a specific part of the body, but they are very unlikely to get rid of all of the cancer. These treatments are more likely to be used to help prevent or treat symptoms or complications from the cancer.

Radiation therapy and/or surgery may also be used in certain situations, such as:

  • When the breast tumor is causing an open wound in the breast
  • To treat a small number of metastases in a certain area, such as the brain
  • To help prevent bone fractures
  • When an area of cancer spread is pressing on the spinal cord
  • To treat a blood vessel blockage in the liver
  • To provide relief of pain or other symptoms

In some cases, regional chemo may be useful as well.

If your doctor recommends such local or regional treatments, it is important that you understand their goalwhether it is to try to cure the cancer or to prevent or treat symptoms.

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Disseminated Tumour Cells As Culprits For Metastatic Recurrence

Metastatic relapse is attributed to the outgrowth of cancer cells that have escaped from the primary tumour and take up residence in secondary sites. Cancer cells that physically detach from a primary source and seed distant sites are known as disseminated tumour cells . The process whereby DTCs transform a localised cancer into a systemic disease is called the metastatic cascade . In the next few sections, the seven key steps comprising this complex biological process are discussed with the goal to shed light on the when and how of DTC dissemination. Importantly, while depicting the metastatic cascade as an orderly series of sequential eventsstarting from the primary tumour and ending in a distant metastatic siteit should be noted that DTC spread can take place through multiple routes and different directions. Accordingly, clinical evidence of self-seedingwhereby a metastatic cell re-infiltrates its primary tumourand of metastasis-to-metastasis spread, has been documented, with one such study in HR+ breast cancer patients reporting a common origin between lymph node and distant metastases in up to 25% of cases.

Fig. 2: Tumour cell dissemination: the route to metastatic success or failure.

The Stages Of Breast Cancer

NOTE: Although a lot of this information is still valid, The American Joint Committee on Cancer has recently updated their classifications for staging breast tumors.

We will be updating all our articles on staging in the near future. In the meantime, please click HERE for a brief summary of the major changes in January 2018.

If a breast biopsy confirms that breast cancer is indeed the diagnosis, the staging process begins.

The stages of breast cancer are really the extent of breast cancer. So, in order to choose and begin the best treatment, it is necessary to stage breast cancer. The staging process shows the progression of breast cancer.

Breast cancer progresses in relatively predictable and consistent ways, so it is possible to categorize breast cancer in terms of stages.

There are basically five stages of breast cancer, with some subcategories .

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How Is Metastatic Breast Cancer Diagnosed

If you have symptoms of metastatic breast cancer, your provider may recommend tests including:

  • Blood tests, including complete blood count and comprehensive metabolic panel.
  • Imaging studies, including MRI, CT, bone scan and PET.
  • Bronchoscopy, which uses a scope to look inside your lungs this can be done if there is a concerning spot in the lungs.
  • Biopsy to remove tissue from a suspicious area and analyze it.
  • A tap to remove fluid from an area with symptoms. For example, pleural tap removes fluid from the lung area. Spinal tap removes fluid from the spinal cord area.

Statistics Dont Account For Late Recurrences

Spying On Breast Cancer Metastasis

When comparing triple-negative breast cancer to positive tumors, its important to keep in mind late recurrences. Most statistics are presented as five-year survival rate, and in this setting, triple-negative breast cancer can look more ominous. But looking at longer periods of time, say 20 years following diagnosis, this may be different.

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Alternative And Complementary Therapies

Some patients with metastatic breast cancer opt to try alternative therapies that are claimed to achieve healing effects similar to scientifically-tested medical approaches, but lack scientific evidence to support those claims. Approaches that are considered alternative therapies when applied to cancer treatment include vitamin therapies, homeopathic treatments, extreme diets, chiropractic treatment and acupuncture.

Some alternative treatments are harmful or even life-threatening. Amygdalin, an extract derived from apricot kernels, exposes the patient to cyanide. Bee venom can cause a life-threatening allergic reaction. Severe dietary restrictions such as Macrobiotic diets can disrupt the bodyâs metabolism and cause dangerous weight loss. People should be aware that foods, vitamins, and other treatments may interfere with the effectiveness of surgery, chemotherapy or radiation. It is essential that patients work with their doctors and openly discuss possible effects of any treatment they are considering. Alternative and complementary therapies are not regulated by the U.S. federal government and may lack quality controls.

When Can Metastatic Breast Cancer Occur

Some people have metastatic breast cancer when they are first diagnosed with breast cancer . This is called de novo metastatic breast cancer.

Most often, metastatic breast cancer arises years after a person has completed treatment for early or locally advanced breast cancer. This may be called a distant recurrence.

A diagnosis of metastatic breast cancer is not your fault. You did nothing to cause the cancer to spread.

Metastatic breast cancers come from breast cancer cells that remained in the body after treatment for early breast cancer. The breast cancer cells were always there but were dormant and could not be detected. For some unknown reason, the cancer cells began to grow again. This process is not well-understood.

Also Check: How Likely Am I To Get Breast Cancer

Functional Stratification: A New Way To Look At Breast Cancer

As mentioned above, current breast cancer staging is heavily dependent upon the evaluation of pathology specimens. However, recent findings suggest that functional classification of breast tumours may become an important addition to risk prediction and prognosis. Results from preclinical animal models suggest that it might be possible to classify breast cancers on a functional basis, as determined by their ability to promote outgrowth of micrometastatic tumour populations at distant sites. Of note, as presented at the recent Nobel Conference on Breast Cancer, we have the ability to use human tumour cell lines and fresh surgical specimens in our xenograft model to test their ability to promote systemic instigation and/or respond to a protumorigenic host systemic environment .

The ability to determine whether or not a given tumour has the potential to promote the dissemination of tumour cells from the primary tumour, support the proliferation of otherwise indolent disseminated cells or activate systemic signalling pathways that recruit bone marrow cells to the developing tumour stroma of a metastatic lesion would have significant implications for treatment strategies . The ability to use tumour tissue in functional assays to predict tumour behaviour may enable more accurate identification of patients with a high likelihood of future relapse, thereby allowing for potentially curative treatment during the therapeutic window in which the disease can be controlled.

Local And Regional Recurrence Of Breast Cancer

7.1: Chapter Introduction

Breast cancer that comes back in the breast, chest, scar or lymph nodes nearby is called a local or regional recurrence. This is not secondary breast cancer. If you have a local or regional recurrence, you may have tests to check the cancer has not spread to other parts of the body.

We have more information about breast cancer recurrence.

See also

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What Investigations Are Necessary For Staging Breast Cancer

Breast cancer staging almost always involves a bone scan, as breast cancer is highly prone to metastasize to the bones.

During this test, medics inject a small amount of a radioactive substance into the bloodstream, where it eventually collects in the bones. A radiation scanner is then able to detect accumulations of tracer substance in the bones.

If breast cancer spreads beyond the breast, 25% of the time it goes into bones first.

Hormone Therapy For Premenopausal Women

For premenopausal women with metastatic breast cancer, hormone therapy almost always begins with ovarian suppression and either an aromatase inhibitor, tamoxifen or other hormone therapy drug.

Ovarian suppression lowers hormone levels in the body so the tumor cant get the estrogen it needs to grow. This may involve surgery to remove the ovaries or, more often, drugs to stop the ovaries from producing hormones.

Combining ovarian suppression and a hormone therapy drug improves survival over either treatment alone .

If breast cancer progressed during past treatment with a hormone therapy drug, the same hormone therapy drug may not be an option for treatment.

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What Should I Ask My Healthcare Provider About Metastatic Breast Cancer

If youve been diagnosed with metastatic breast cancer, ask your provider:

  • What are my treatment options?
  • What is my prognosis?
  • What side effects can I expect?
  • Will complementary therapy help me feel better?
  • What if I want to stop treatment?
  • How can I feel my best during treatment?

A note from Cleveland Clinic

Metastatic breast cancer is advanced breast cancer. Providers classify it as stage 4 breast cancer. It happens when cancer cells, often left behind after previous breast cancer treatment, start to spread to other parts of the body. While there is no cure for metastatic breast cancer, treatment can prolong your life and help you feel better. There are many medications available, so if one treatment isnt working, your care team can try a different approach. If you notice any symptoms or dont feel your best, especially if youve undergone breast cancer treatment in the past, talk to your healthcare provider.

Last reviewed by a Cleveland Clinic medical professional on 04/14/2021.

References

Mechanism In Brain Metastasis

What Does Metastatic Breast Cancer Mean To You?

The brain is a unique organ for metastasis, since the breast-tumor cells have to pass the bloodâbrain barrier to form micrometastases.

CD44

CD44 is a receptor for hyaluronic acid, involved in cell adhesion by binding to specific extracellular matrix components. A proposed mechanism for the function of CD44 is to regulate the adhesion of circulating cancer cells in the brain to the endothelium at the secondary site with the help of a hyaluronate matrix ligand or by its cytoplasmic attachments to actin-associated proteins of the merlin/ezrin/radixin/moesin family.

Sialyl transferase

Cell-surface sialylation has been implicated in cellâto-cell interactions, and over-expression of a brain sialyltransferase in breast-cancer cells is a mechanism highlighting the role of cell-surface glycosylation in organ-specific metastatic interactions. Breast-cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of BBB-crossing and brain colonization.

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Drugs Targeting Metabolism In Metastatic Breast Cancer

Table 2 Current metabolic interventions in metastatic breast cancer.

Metabolic inhibitors combined with checkpoint inhibitors holds promise to enhance the efficacy of immunotherapy and the relationship of tumor-intrinsic metabolism and successful immunotherapy is being explored. Tumor-imposed metabolic restrictions can mediate T cell hyporesponsiveness during cancer. Checkpoint blockade antibodies against CTLA-4, PD-1, and PD-L1, can restore glucose in tumor microenvironment, permitting T cell glycolysis and IFN- production, and blocking PD-L1 directly on tumors dampens glycolysis by inhibiting mTOR activity and decreasing expression of glycolysis enzymes . Because breast cancer immunotherapy is in the ascendant, understanding the metabolic dependence between infiltrating immune cells and cancer is an important direction for future research.

How Breast Cancer Spreads

Breast cancer can spread through the lymphatic system, the bloodstream, or by local invasionfor instance, when cancer cells actually invade nearby tissues, such as the chest wall or ribs.

When breast cancers spread and enter the lymphatic system, they usually first arrive at nearby lymph nodes and may still be early-stage.

Metastatic breast cancer is the same thing as stage 4 breast cancer and is considered the most advanced stage. It refers to breast cancers that have spread beyond the breast and nearby lymph nodes to other regions of the body, which are called distant metastases.

While treatment options for metastatic breast cancer are similar no matter where cancer has spread, some treatments are used for specific sites of metastasis as well .

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Cancer Invasion And Metastasis: The Role Of Cell Adhesion Molecules

Cancer metastasis is the spread of cancer cells to tissues and organs beyond where the tumor originated and the formation of new tumors is the single event that results in the death of most patients with cancer. At the time of cancer diagnosis, at least half of the patients already present clinically detectable metastatic disease. A higher number of patients will also have micrometastases that would be beyond conventional detection techniques. Thus, metastasis is the most life threatening event in patients with cancer. The process is composed of a number of sequential events which must be completed in order for the tumor cell to successfully metastasize, the so called metastatic cascade. This process contributes to the complexity of cancer as a multiplex disease. During the metastatic cascade, changes in cell-cell and cell-matrix adhesion are of paramount importance.

The metastatic cascade is therefore dependent on the loss of adhesion between cells, which results in the dissociation of the cell from the primary tumor, and subsequently the ability of the cell to attain a motile phenotype via changes in cell to matrix interaction.

Most Common Places It Spreads

Schematics of the process of metastasis. (a) Formation ...

It’s still breast cancer, even if it’s in another organ. For example, if breast cancer spreads to your lungs, that doesn’t mean you have lung cancer. Although it can spread to any part of your body, there are certain places it’s most likely to go to, including the lymph nodes, bones, liver, lungs, and brain.

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