Can Breast Cancer Metastasis To Bone

Local Or Regional Treatments For Stage Iv Breast Cancer

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.

Box 1 How Rapid Autopsy Studies Can Inform On Metastatic Dissemination And Relapse

Definitions

• Rapid autopsy: rapid post-mortem collection, examination and biobanking of tissuesfresh, snap-frozen and fixedfrom deceased patients shortly after death.

• Rapid autopsy cancer programme: coordinated effort among oncologists, pathologists and scientists aimed at collecting specimens from cancer patients within a post-mortem interval of 68h before key biological information within the tissues of interest is lost.

Advantages

• Multiregional biopsies: to conduct extensive, spatial sampling of tissuesprimary and metastatic, cancerous and normalfor in-depth, high-resolution multi-omics analysis.

• Physiological model: to analyse DTCs in their natural metastatic niche.

• to generate novel, ex vivo living patient-derived modelsautopsy-derived xenografts and organoids of metastatic tumours from sites that would otherwise be difficult to sample for functional evaluation .

• Cancer evolution: to study the phylogenetic relationship of each sampled site to each other and infer the complete clonal evolution of a neoplasm.

• Dormancy: to examine why some DTCs lodged in certain organs of the human body become dormant for years to decades.

• Drug resistance: to study why DTC spread across different sites responds differently to therapy, with some developing resistance and others remaining sensitive to treatment.

• Recurrence: to understand why only some DTCs residing in certain sites of the human body give rise to active metastases, ultimately responsible for patients relapse.

Advanced Cancer That Progresses During Treatment

Treatment for advanced breast cancer can often shrink the cancer or slow its growth , but after a time, it tends to stop working. Further treatment options at this point depend on several factors, including previous treatments, where the cancer is located, and a woman’s age, general health, and desire to continue getting treatment.

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Symptoms Of Secondary Breast Cancer

Secondary breast cancer means that a cancer that began in the breast has spread to another part of the body. Secondary cancer can also be called advanced or metastatic cancer.

It might not mean that you have secondary breast cancer if you have the symptoms described below. They can be caused by other conditions.

Origin And Characterization Of Cafs In The Tumor Microenvironment

The origin of CAFs in the tumor microenvironment remains to be elucidated, but they might be derived from resident fibroblasts , actively recruited bone marrow-derived cells or cells that undergo epithelial-mesenchymal transition .

Due to the phenotypical and functional heterogeneity of CAFs there are no unique markers to identify them but commonly used ones include SMA, fibroblast-specific protein1 , fibroblast activation protein , platelet derived growth factor receptors , vimentin, and tenascin C . Several in vitro studies demonstrate that MSCs can differentiate into SMA -expressing myofibroblasts upon cancer cell stimulation . For instance, studies by Mishra and colleagues show that human bone marrow-derived MSCs can acquire a CAF-like, myofibroblastic phenotype upon prolonged stimulation with conditioned medium from MDA-MB-231 breast cancer cells. Importantly, these cells expressed CAF markers including SMA, SDF-1, vimentin, and FSP as determined by immunofluorescence staining. Gene expression analysis revealed that cancer-conditioned medium upregulated the expression of CAF-associated genes including SDF-1, platelet derived growth factor and MMP9, suggesting that exposure to cancer cells induces hMSC differentiation into a CAF-resembling state .

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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.

High Blood Calcium Levels

When cancer spreads to the bones, too much calcium from the bones can be released into the bloodstream. This is called hypercalcemia.

High blood calcium levels can cause problems such as

• Constipation
• Feeling thirsty all the time and drinking lots of liquids
• Muscle weakness
• Coma
• Kidney failure.

Treatment includes giving large amounts of intravenous fluids to protect the affected kidneys and medicines such as bisphosphonate drugs to bring blood calcium levels down quickly. Once the calcium level is back to normal, treating the cancer can help keep the calcium level from getting too high again.

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Signs That Breast Cancer Has Spread To The Bone

Most aches and pains arent cancer, stresses Huston. But its important to keep an open and honest dialogue with your doctor about any unusual or persistent discomfort you may be having. He or she can determine if getting images is appropriate to rule out bone metastasis. Here are the symptoms of bone metastasis to look out for:

If you report any of the above symptoms to your doctor, he or she may want to do a thorough physical exam, blood tests, and a bone scan to check for bone metastasis. Depending on the results and where or how severe the bone pain is, he or she may also order an X-ray, PET scan, or CT scan. In some cases, a tissue biopsy is also done to confirm the diagnosis.

How Are They Treated

Treatment for bone mets is multi-faceted and often involves pain medication, bisphosphonate treatments, radiation, systemic chemotherapy and, occasionally, surgery. Treatment varies per individual, based on need for symptom alleviation, extent of bone mets, the presence or absence of soft-tissue involvement as well as particular characteristics of the tumor . Because bone mets can be painful and even disabling, pain management is critical to maintaining well-being. It is important to report discomfort to treatment providers. In treating bone mets, the goals include restoring comfort and mobility, preventing new tumors from developing and maintaining stability. Even though bones mets may cause considerable pain and cannot be cured, effective treatment allows people to live well with bone mets.

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Osteoclasts And The Vicious Cycle Model Of Bone Loss

The entry of breast cancer cells into the bone micro-environment synergistically increases the complexity of cell-cell interactions. A working model to describe the bone remodeling compartment in the presence of metastatic cancer cells has been referred to as the ‘vicious cycle of bone metastasis’ . There are many excellent reviews describing this paradigm from its inception in the 1990 s. The minimal essential components are osteoblasts, osteoclasts, tumor cells and the mineralized bone matrix. According to this paradigm, the tumor cells produce a variety of growth factors, most notably parathyroid hormone-related protein . The role of PTHrP in bone metabolism is not fully understood, but it is known to cause upregulation of RANKL and downregulation of OPG , thus enhancing osteoclast function leading to bone degradation. In the process, growth factors stored in the matrix, such as transforming growth factor -, vascular endothelial growth factor , insulin-like growth factors , bone morphogenic proteins and fibroblast-derived factors, as well as calcium, are released into the bone microenvironment. These factors can stimulate the tumor cells to proliferate and produce more growth factors and more PTHrP, further perpetuating the vicious cycle of bone metastasis.

Symptoms If Cancer Has Spread To The Bones

You may have any of these symptoms if your cancer has spread to the bones:

• an ache or pain in the affected bone
• breaks in the bones because they are weaker
• breathlessness, looking pale, bruising and bleeding due to low levels of blood cells – blood cells are made in the bone marrow and can be crowded out by the cancer cells

Sometimes when bones are damaged by advanced cancer, the bones release calcium into the blood. This is called hypercalcaemia and can cause various symptoms such as:

• tiredness

• Find out more about cancer that has spread to the bones

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Can Metastatic Breast Cancer Go Into Remission

Metastatic breast cancer may never go away completely. But treatment can control its spread. Cancer may even go into remission at some points. This means you have fewer signs and symptoms of cancer.

A treatment break may be considered in certain situations, including if remission occurs or if someone is experiencing intolerable side effects. A pause in treatment can help you feel your best and improve your quality of life.

Osteoblasts As Novel Target To Treat Bone Metastasesbone Anabolic Treatment

Advancements have been made in limiting progression of breast cancer bone metastasis and novel therapeutic agents are emerging . However, once osteolytic lesions have been developed, the disease remains incurable and treatment is restricted to palliative care. This often includes the administration of the anti-resorptive bisphosphonate Zoledronic acid, or of the RANKL inhibitor Denosumab to reduce the cancer-induced bone destruction . Further experimental approaches to target osteoclasts in metastatic bone disease include Cathepsin-K and c-Src inhibitors . However, these agents are not able to restore the cancer-induced bone destruction. Therefore, augmenting osteoblast function has been proposed as a potential approach to restore bone integrity in the context of metastasis-induced osteolytic lesions .

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Can Earlier Detection Of Recurrence Improve Breast Cancer Outcomes

The risk of metastatic relapse weighs heavily on the minds of patients, physicians and caregivers for years, sometimes decades, after treatment of the primary tumour is complete. Nearly 17 million cancer survivors are living in the United States, 3.9 million of whom are breast cancer survivors, and repeated monitoring for cancer recurrence in these individuals presents a significant challenge to healthcare delivery systems. For breast cancer patients, current American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines limit follow-up care to mammography, medical history and physical exam, stating that in the absence of clinical signs and symptoms suggestive of recurrent disease, there is no indication for laboratory or imaging studies for metastases screening., Despite these guidelines, however, many patients receive high-cost imaging analysis and tumour marker blood tests during routine follow-up exams, exposing them to radiation and increasing healthcare costs.,,, So, what has led to the current precarious balance between the desire to detect recurrence early and clinical guidelines that limit the use of diagnostic tests?

Table 1 Exploiting tumour dormancy as a window of therapeutic opportunity to target MRD.

Will I Need More Than One Treatment For Metastatic Breast Cancer

Medications are important for metastatic breast cancer to help control its spread. Resistance to therapies may develop, which can lead your care team to recommend a change in treatment.

When you start a treatment regimen, you and your care team will see how:

• The cancer responds to the therapy.
• The side effects impact you.

If the treatment isnt working or the side effects are unbearable, your care team can discuss switching the treatment method. They may recommend a different drug, dosage or schedule.

There are many treatments available. If one therapy isnt working for you for whatever reason, there is usually another one you can try.

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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

Cellular And Tumour Mass Dormancy

Two different models of tumour dormancycellular and tumour mass dormancyhave been proposed. Cellular dormancy refers to the presence of solitary or small cell clusters of DTCs that exist in a G0/G1 growth-arrested state and result from quiescence, senescence or differentiation. An inability to properly adhere to the ECM,, reduced signalling through the phosphatidylinositol 3-kinase /AKT pathway and a low ratio of the extracellular signal-regulated kinase to the stress-induced kinase p38, are some of the plethoras of predominantly cell-intrinsic mechanisms that have been reported to induce cellular dormancy. On the other hand, escape from cellular dormancy has been shown to occur upon increased matrix stiffness through TGF1 expression, following the release of neutrophil extracellular traps by inflammatory neutrophils, and as a result of aberrant activation of the adhesion protein vascular cell adhesion protein 1 in indolent breast DTCs lodged in the bone marrow via engaging 41-expressing osteoclasts.

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Systemic Treatments For Stage Iv Breast Cancer

Treatment often continues until the cancer starts growing again or until side effects become unacceptable. If this happens, other drugs might be tried. The types of drugs used for stage IV breast cancer depend on the hormone receptor status and the HER2 status of the cancer:

Hormone receptor-positive cancers

Women with hormone receptor-positive cancers are often treated first with hormone therapy . This may be combined with a targeted drug such as a CDK4/6 inhibitor, everolimus or a PI3K inhibitor.

Women who havent yet gone through menopause are often treated with tamoxifen or with medicines that keep the ovaries from making hormones along with other drugs. Because hormone therapy can take months to work, chemo is often the first treatment for patients with serious problems from their cancer spread, such as breathing problems.

Hormone receptor-negative cancers

Chemo is the main treatment for women with hormone receptor-negative cancers, because hormone therapy isnt helpful for these cancers.

HER2-positive cancers

Trastuzumab may help women with HER2-positive cancers live longer if its given along with chemo or with other medications such as hormonal therapy or other anti-HER2 drugs. Pertuzumab , another targeted drug, might be added as well. Other options might include targeted drugs such as lapatinib or ado-trastuzumab emtansine .

HER2-negative cancers in women with a BRCA gene mutation

HER2-negative breast cancers in women with a PIK3CA mutation

Relieving Symptoms Of Advanced Breast Cancer

Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases may be treated with radiation therapy, drugs called bisphosphonates such as pamidronate or zoledronic acid , or the drug denosumab . For more, see our information about the treatment of bone metastases.

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What Is A Metastasis

Metastasis is a word that describes the spread of cancer from its original site to another part of the body. Metastasis happens when cells break away from the original cancer site and travel to other areas of the body through the bloodstream or the lymph system. Cancer cells then settle in different tissues or organs, where they grow and form a new tumour . When breast cancer is found in parts of the body other than the breast it is called metastatic breast cancer.

A bone metastasis from breast cancer is made up of breast cancer cells. Bone is one of the most common places for breast cancer to spread.

Is Stage 4 Breast Cancer Curable

Theres currently no cure for stage 4 breast cancer, but with treatments it can be kept under control, often for years at a time.

People with metastatic breast cancer need to receive treatments for the rest of their lives. If a certain treatment stops being effective, another treatment regimen may be tried.

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Focusing On Next Steps

The researchers will continue to investigate the mechanisms uncovered in this study using the mouse model and tissue from patients with breast cancer. We are interested in seeing whether disconnecting breast cancer cells from an environment that harbors them in a clinically dormant state could expose the vulnerabilities of these cells, said Dr. Sipkins.

Future studies, added Dr. Price, will also look at what happens to breast cancer cells that are mobilized out of the bone marrow.

More research is needed to ensure that breast cancer cells forced out of the bone marrow do not travel through the bloodstream to another organ, such as the brain, noted Dr. Dunbar. The current study, she continued, will inform the direction of future research.

The more we know about how breast cancer cells spread to bone, the more we will be able to explore ways to prevent and treat bone metastases, she said.

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