Are Micrometastatic Cells Metastatic Progenitors
Bone marrow is the host organ of breast cancer metastases, which is the most accessible tissue for analysis, as liquid aspirates can be performed under local anaesthesia or during primary surgery. It is of critical importance to determine whether DTC are the metastatic progenitors of bone and/or distant non-bone metastasis. A negative answer would limit the accuracy of bone marrow DTC as a biological model, a target for adjuvant treatment and a marker of response. Paget was the first to describe the non-random growth of metastases, and the sustaining molecular determinants of cancer cell homing have been recently characterised. If BM DTC are derived from the specific spread of a few tumour subclones into flat bones, their ability to recirculate to other organs would be somehow limited. Consequently, their detection would be linked to an increase of bone metastasis at primary relapse in patients, but not to that of other metastatic sites. Micrometastases retained their clonogenic and tumourigenic capacities in many biological reports. Clinical studies have reported a link between BM DTC and the onset of bone metastasis, strongly supporting the idea of local growth of DTC into macrometastases.
Micrometastasis And Cancer Stem Cells
The role of cancer stem cells in the establishment of metastasis remains controversial in many theoretical proposals and reviews. Experimentally, CD44+/CD24/low cancer cells, a phenotype associated with a stem cell pattern, exhibit an invasive phenotype, which is a prerequisite to metastasis. In a report on 50 cases, most BM micrometastatic breast cancer cells exhibited a stem cell-like immunohistochemical phenotype.
Symptoms Of Bone Marrow Cancer
Some of the other bone marrow cancer symptoms are: pain, a hard lump on the affected bone tenderness, stiffness, or swelling in the bone, usually near or inside a joint, frequent fractures for no reason, anemia, or low red blood cells, a lowering in the resistance to infections, dizziness, shortness of breath, and general weakness.
- Weight loss
- Nausea or vomiting
- Loss of appetite
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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, the HER2 status of the cancer, and sometimes gene mutations that might be found.
Deployment Of Chemotherapy/radiation Therapy
Next, elevated doses of chemotherapy are given to the person or doctors opt for radiation therapy. This essentially eliminates abnormal stem cells along with blood cells. Your regular bone marrow is eliminated. Then the blood counts diminish to low levels.
At this stage, IV fluids are given to flush out the kidneys and reduce damage. Nausea control drugs are also administered at this time. Chemotherapy sometimes leads to vomiting. After this, the doctors tend to keep the patient isolated in a medical facility since the health state is fragile. This is necessary until the new bone marrow develops in a body.
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Metastatic Breast Cancer: What You Should Know
What does it mean to have metastatic, or stage 4, breast cancer? A Rogel Cancer Center oncologist explains the diagnosis and how its treated.
After hearing a diagnosis of metastatic breast cancer, a rush of questions emerges. But often, its not until long after leaving the doctors office.
Metastatic means the cancer has spread beyond the breast and immediate lymph nodes to other organs or tissues in the body, most often the bones, brain, lungs or liver. Its considered stage 4 breast cancer, which means the cancer has progressed to its most advanced stage.
But even though its moved to other organs, it still behaves like breast cancer and is treated with breast cancer therapies.
More than 154,000 U.S. women are estimated to have metastatic breast cancer, according to the Susan G. Komen organization. Men can have metastatic breast cancer too, but its rare.
To help patients fill in information gaps, N. Lynn Henry, M.D., Ph.D., the breast oncology disease lead for the University of Michigan Rogel Cancer Center, explains the nuances of stage 4 metastatic breast cancer.
What are the differences between metastatic breast cancer, stage 4 breast cancer and advanced cancer?
If any doctor uses the term advanced, ask for clarification, Henry adds.
When does metastatic breast cancer appear?
What are the symptoms?
Symptoms of bone metastases:
Can Metastatic Breast Cancer Be Cured
There is no cure for metastatic breast cancer. Once the cancer cells have spread to another distant area of the body, its impossible to get rid of them all. However, the right treatment plan can help extend your life and improve its quality.
Metastatic breast cancer treatment aims to shrink tumors, slow their growth and improve your symptoms.
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What Happens Before The Transplant
A number of tests are performed before the bone marrow transplant procedure to make sure you are physically able to undergo a transplant. These tests also help the transplant team identify and treat any potential problems before the transplant.
Your heart, lungs and kidney function will be tested. Your doctor may also order blood tests, a CAT scan, and a bone marrow biopsy. A complete dental examination is required before the procedure to minimize your risk of infection, and other precautions will be taken as necessary to minimize the risk of infection.
The tests required before the bone marrow transplant are usually done on an outpatient basis. Your transplant coordinator will help arrange these tests for you.
Osteonecrosis Of The Jaw
In rare cases, with either bisphosphonates or denosumab, a disorder called osteonecrosis of the jaw may occur . This is mostly a concern for people who take frequent doses of one of these drugs for long periods of time.
To reduce the risk of osteonecrosis of the jaw, its recommend you have a dental exam and take care of any dental work before starting treatment with bisphosphonates or denosumab .
Talk with your oncologist before getting any dental work while youre on bone-strengthening therapy. Also, tell your dentist you are on these medications.
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How Is Stage 4 Breast Cancer Treated
The aim of treatment is to improve the quality and length of life of people with stage 4 breast cancer. Each person will be treated differently based on the disease characteristics and the intended goals of treatment.
Most treatments aim at decreasing the tumor burden and stabilizing the disease. In general, stage 4 cancer treatmentsalthough they may extend life in a significant number of peopleare considered palliative . This is because only a handful of people treated at this stage are cured of their disease.
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.
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The 4 Stages Of Breast Cancer
The four stages of breast cancer include
- Stage I: It is divided into two groups.
- Stage IA: Cancer is 2 cm or smaller and has not spread outside the breast.
- Stage IB: Cancer has spread to the lymph node and is between 0.2 and 2 mm in size.
There is one more stage called stage 0 or carcinoma in situ. It means the initial stage where the cancerous cells are confined to their origin and have not acquired the invasive character yet.
The staging system most often used for breast cancer is the TNM system of the American Joint Committee on Cancer . In this, breast cancer staging may be of two types.
Exploring Mechanisms Of Metastasis
In humans, breast cancer can recur in patients more than a decade after the disease has been treated. In most of these cases, the cancer has metastasized to bone.
Our study addresses a difficult clinical problemthe disease can recur in patients who thought they had been cured of breast cancer years earlier, explained Dorothy A. Sipkins, M.D., Ph.D., of the Duke Cancer Institute, who led the research.
Past work had suggested that these late recurrences may be caused by the emergence of breast cancer cells that had previously spread to the boneknown as micrometastasesbut had remained dormant. But the mechanisms involved in the spread of breast cancer to bone are poorly understood.
E-selectin is an adhesion proteina protein that helps cells bind to other cells and to their surroundingsthat is present on the surfaces of cells lining blood vessels. Because the protein has been associated with the homing of hematopoietic stem cells into the bone marrow at certain regions, or niches, where it is highly expressed, the researchers investigated whether breast cancer cells could co-opt E-selectin to also mediate their movement into the bone.
E-selectin is a sticky protein expressed by certain blood vessels that serves as a portal into the bone marrow, explained Cynthia Dunbar, M.D., of the Hematology Branch at the National Heart, Lung, and Blood Institute, who was not involved in the research. The bone marrow seems to provide a protective home for breast cancer cells.
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What Is The Prognosis For Stage Iv Breast Cancer
Whether a patients metastatic breast cancer is the oligometastatic type or the most challenging, widespread sort, the best possible care addresses the patient as a unique individual. And according to Habibi, there are more reasons for hope than ever before.
Advancements in treatment options have extended the survival of patients with metastatic breast cancer, which had a stigma of being untreatable just a generation ago.
Even within the last decade, all aspects of care have seen a good amount of progress. Better diagnostic tests such as improved PET and CT scans are helping us find cancers faster and initiate treatment. And targeted therapies such as radiation, surgery and systemic treatments have seen improvements as well.
Aggressive And Advanced Metastatic Breast Cancer
Habibi says the most extreme situations involve patients who are diagnosed with a very fast, aggressive breast cancer that has already spread to multiple organs and begins to overwhelm the body. For those patients, palliative care is important, concentrating on local control, pain management and avoiding bleeding and infection.
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Breast Cancer Subtypes Hormonal And Her2 Status
Although the term breast cancer is used in general, there are many different sub-types of breast cancers. The sub-types behave in different ways, with some responding better to treatments and some growing and spreading at faster rates.
Obviously, the sub-type of breast cancer affects survival rates.
There are 5 molecular types of breast cancer:-
Why Does My Provider Need To Test The Metastatic Tumor
Your care team will test the metastases to figure out the biology of the tumor, which can help guide your treatment plan. Providers may test tumors for:
- Hormone receptor status: If the cancer is hormone receptor-positive, hormonal therapy may be your first treatment.
- HER2 status: Human epidermal growth factor receptor 2 is a protein that is overexpressed on some breast cancer cells. HER2-positive cancer responds to specific HER2-targeted therapies.
- PIK3CA gene mutation: If a tumor is hormone receptor-positive and HER2-negative, your provider may test for this gene mutation. Specific targeted therapies can be used to treat tumors with this mutation.
- PD-L1 status: Tumors that are hormone receptive-negative and HER2-negative may be tested for PD-L1 status. If the PD-L1 test is positive, you may be recommended to receive a combination of immunotherapy and chemotherapy.
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Mechanisms Of Breast Cancer Metastasis
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 host factors. The host factors are the characteristics of the non-malignant cells and the general biological environment surrounding the malignant breast tumor.
Sometimes the host factors are 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.
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.
What’s The Life Expectancy Of Bone Metastasis
The prognosis of cancer that has spread to the bones varies according to many factors. With bone metastases, life expectancy depends on the type of primary cancer, your response to treatment, bones affected, severity of bone damage, etc. Various treatments for bone metastases can help relieve symptoms and prolong life.
However, it should be noted that when cancer has invaded the bones, the chances for living more than 5 years are generally poor. Patients may be able to survive 6 months to 2 years with proper treatments. In general, patients with bone metastases from breast or prostate cancer tend to survive longer than those from lung cancer. In addition, emotional support from family members and friends plays an important role in longer life expectancy.
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. Also, the patients age and general health and the types of treatment the patient has had in the past.
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- 1Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico , Roma, Italy
- 2Universita Cattolica Del Sacro Cuore, Roma, Italy
- 3Division of Gynecologic Oncology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
Bone Marrow Cancer Stages
Bone marrow cancer is usually divided into 3 stages by doctors, depending upon the condition of the person.
- Stage 1: Patients suffering from multiple myeloma dont show any symptoms initially as the number of cancer cells in the body is not very high. In the first stage, the number of red blood cells maybe just within or below the required range. Another symptom could be lower level of M protein in the blood and urine.
- Stage 2: The number of cancer cells in the body during this stage is much higher than the first stage. In case the functioning of the kidneys get affected, the prognosis gets worse. This stage patients are those whose symptoms lie neither in the first or third stage.
- Stage 3: This is usually the most harmful and terminal stage of the cancer, wherein the number of cancer cells in the body is very high. Symptoms of this stage include Anemia, Hypercalcemia, bone damage and high levels of M protein in the blood and urine.
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