What Is The Term For The Time It Takes For A Tumor To Double In Size
Tumor doubling time is the period of time that it takes for the tumor to double in size. Since it would be unethical to leave a cancer untreated to see how rapidly it grew, doubling time is estimated in a number of ways. Looking at these estimates, however, doubling times have varied widely from study to study.
Microenvironmental Regulation Of Tumor Dormancy
Increasing experimental evidence suggests that local microenvironmental influences on the primary tumor have persistent effects on tumor cell homing, dormancy status, and chemotherapy resistance in the bone metastatic site. The C-X-C motif chemokine ligand 12 :C-X-C motif chemokine receptor 4 signaling axis is one of the most well-established mechanisms that promotes breast cancer cell homing and colonization from the primary tumor to the bone . This signaling cascade is often initiated by CXCR4 overexpression on breast cancer cells, making them more susceptible to priming by CXCL12-expressing cancer-associated fibroblasts in the primary tumor and colonization of the CXCL12-rich bone marrow . Hypoxia, or low oxygen tensions, in the primary tumor has been shown to generate a sub-population of post-hypoxic DTCs in breast cancer that, following dissemination, highly express a NR2F1-driven pro-dormancy gene program and are capable of evading chemo-therapy . Recently, breast cancer cells that survived adjuvant chemotherapy treatment in vitro exhibited sustained activation of the interferon regulatory factor 7 /interferon beta /interferon alpha and beta receptor signaling axis, which elicited a state of immunological dormancy and chemotherapy resistance . Together, these findings begin to reveal the significant influence of the primary tumor microenvironment and adjuvant therapy on the subsequent dormancy phenotype and survival of DTCs at distant sites.
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
- Feeling thirsty all the time and drinking lots of liquids
- Muscle weakness
- 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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Extracellular Matrix Metalloproteinase Inducer
A newly discovered molecule downstream of RANKL is extracellular matrix metalloproteinase inducer /CD147, a cell surface glycoprotein that is known to induce MMPs and VEGF . While EMMPRIN is produced normally during tissue remodeling, it increases during tumor progression and metastasis. This molecule is also produced by metastatic breast cancer cells . Increased production of EMMPRIN in turn leads to increases in VEGF and MMPs. Both RANKL and VEGF can induce osteoclast formation , and MMPs play a role in bone matrix degradation.
Which Patients Benefit Most From Bisphosphonate Use
Randomized controlled trials have shown that the beneficial effects of bisphosphonates are time-dependent significant benefits were seen only after 6 months of treatment 20. Therefore, looking at survival times for patients with breast cancer is important before starting them on bisphosphonate treatment.
A retrospective analysis involving 859 patients who developed bone metastases from breast cancer showed that, as compared with patients with bone and visceral metastases, patients with disease confined to the skeleton were most likely to develop a sre34 . The difference with regard to the development of a sre was probably attributable to the survival difference between the groups . Patients with bone-only disease may therefore benefit most from treatment with bisphosphonates, because they are most likely to live long enough to experience the time-dependent benefits of bisphosphonates 34. Notably, Canadian treatment guidelines do not encourage the use of bisphosphonate treatment in patients with a life expectancy below 6 months and who are asymptomatic from their bone metastases 3.
Further prospective studies are needed to identify the subgroup of patients most likely to develop sres and therefore to benefit most from bisphosphonate treatment. In an attempt to develop a prediction model, our group is currently analyzing baseline clinical characteristics in 100 patients on bisphosphonates at three cancer centers 35.
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When Can Bone Metastases Occur
Bone metastases may be present when metastatic breast cancer is first diagnosed, or the cancer may spread to the bones later.
The bones are the first site of metastases for almost half of women diagnosed with metastatic breast cancer . For many of these women, the bones will be the only site of metastases .
A New Treatment Meets Achieves Both Purposes
There is a revolutionary new noninvasive treatment to ease pain and put the brakes on local bone mets by ablating the bone tumor . It is called MR-guided Focused Ultrasound .
MRgFUS begins with identification and planning. Magnetic resonance imaging reveals the location, size and extent of the lesion. This same imaging allows the physician to plan strategically targeted delivery of ultrasound to the lesion. The ultrasound beams are aimed from numerous different directions, and each one passes harmlessly through skin and other tissues. Then, when the beams converge, they generate a short blast of lethal heat at the point where they meet. This heat destroys the bone mets at that site, and deadens the nerves that send pain messages to the brain.
Within 3-7 days, most patients have significant pain reduction in many cases, almost none.
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Can Cancer Cause A Coma
Once infiltrated by cancer, your bones can quickly lose calcium and cause hypercalcemia, a condition in which calcium is released into the blood. If not treated, hypercalcemia may lead to coma and kidney damage. The loss of bone calcium is particularly serious for older women, who have naturally weaker bones.
Symptoms If Cancer Has Spread To The Lymph Nodes
Lymph nodes are part of a system of tubes and glands in the body that filters body fluids and fights infection.
The most common symptom if cancer has spread to the lymph nodes is that they feel hard or swollen. You might have any of the following symptoms if your cancer has spread to the lymph nodes:
- a lump or swelling under your armpit
- swelling in your arm or hand
- a lump or swelling in your breast bone or collar bone area
One of the first places breast cancer can spread to is the lymph nodes under the arm on the same side as the breast cancer. This is not a secondary cancer.
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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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Symptoms And Diagnosis Of Bone Metastasis
A sudden, noticeable new pain is the most common symptom of breast cancer that has spread to the bone. The pain may come and go at first but can become constant over time. It can be hard to tell the difference between bone metastasis pain and arthritis pain or exercise strain. If the pain feels just as bad or even worse when you rest or lie down, it can be a sign of a problem. Its a good idea to see your doctor right away if it is bone metastasis, prompt treatment can prevent a fracture down the road.
Complications of bone metastasis are called skeletal-related events and can include the following:
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What Is Metastatic Breast Cancer In Bones
Metastasis describes the spread of cancer from where it started to another part of the body. This happens when cancer cells break from the primary tumor and enter the lymph system or bloodstream. From there, they can travel throughout the body and form new tumors.
Metastatic breast cancer in bones is not the same as bone cancer. Its made up of breast cells, not bone cells. Its also called stage 4 or advanced breast cancer.
A 2019 research review showed that bone is the most common site of breast cancer metastasis. Breastcancer.org says that for more than half of women with metastatic breast cancer, bones are the first site of metastasis. The bones most likely to be affected are:
- long bones in your arms and legs
Other common sites of breast cancer metastasis include your liver and lungs.
Signs and symptoms vary depending on where the cancer has spread and how big the tumors are.
How Can I Take Care Of Myself While Living With Metastatic Breast Cancer
Living with metastatic breast cancer can be challenging. Your care team can help provide physical and emotional support. Talk to them about how you can:
- Eat the most nutritious diet for your needs.
- Exercise regularly.
- Get emotional support, including finding support groups.
- Reach out for help from friends, family and loved ones.
- Find mental health services.
- Find complementary therapies.
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Why Does Metastatic Breast Cancer Happen
Most often, metastatic cancer occurs because treatment didnt destroy all the cancer cells. Sometimes, a few cells remain dormant, or are hidden and undetectable. Then, for reasons providers dont fully understand, the cells begin to grow and spread again.
De novo metastatic breast cancer means that at the time of initial diagnosis, the breast cancer has already spread to other parts of the body. In the absence of treatment, the cancer spreads.
There is nothing you can do to keep breast cancer from metastasizing. And metastatic breast cancer doesnt happen because of something you did.
Most Common Places It Spreads
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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How Breast Cancer Spreads
A diagnosis of breast cancer starts a chain of research, further tests, and anxiety. Although mortality rates have gradually been dropping, an understandable worry is the fear of the disease having spread microscopically at the time of diagnosis.
Thankfully, screening programs work, and most breast cancer is detected early when it is highly curable. However, if left untreated, breast cancer can metastasize . Most commonly, it travels first to the lymph nodes in the armpit area. Once it enters the lymphatic system, it can spread to other areas of the body, including organs and bones. Also, some types of breast cancer can enter the bloodstream, using the circulatory system to spread to other areas.
Breast cancer that spreads to the bone is particularly feared, since weakened bones and severe bone pain can literally become crippling. However, the odds are greater than 80% against developing bone mets. According to one analysis, an average of 12% of women initially diagnosed with Stage I-III disease developed bone mets during 60 months of follow up.1
Understanding Your Fracture Risk
Women with both early and advanced stages of breast cancer have an increased risk for bone fractures, which can have a serious impact on mobility and lifestyle in the future. Eating a healthy diet and getting plenty of exercise are important steps to prevent fractures. Screening for bone health in women with breast cancer is also a high priority. The best way to gauge bone health is by having a bone density test, a simple scan that measures bone strength and helps detail the risk for future breaks and osteoporosis.
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Models To Investigate Tumor Dormancy
One of the major limitations to studying tumor dormancy is the lack of reliable, clinically relevant models. Numerous in vitro and in vivo models have been established in order to study the effects of the bone marrow microenvironment on breast cancer cell behavior and metastatic progression . Transgenic models such as MMTV-PyMT and MMTV-HER2 provide the opportunity to study spontaneous metastasis to bone and have shown that dissemination of tumor cells occurs in parallel with primary tumor development . DTCs enter an indolent state prior to reactivation in the bone marrow in these models . However, transgenic models often require many months to detect DTCs, do not reliably metastasize to the bone, or require surgical removal of the primary tumor to allow enough time for establishment of micrometastatic disease. While these models quite accurately recapitulate the prolonged latency periods observed in the human condition, the majority of in vivo studies rely on the inoculation of tumor cells directly into the circulation through the left cardiac ventricle , iliac artery , or tail vein . Importantly, these experimental metastasis models mimic bone colonization rather than the entire metastatic cascade and often utilize highly aggressive cell lines that develop metastases without a latency period . Together, the aforementioned limitations make it difficult to investigate tumor dormancy and metastatic outgrowth in these models.
How Is Metastatic Breast Cancer In Bones Diagnosed
Your doctor will likely start with a discussion of your symptoms and a physical examination.
Diagnostic testing may include blood tests to find out if your blood has too much calcium or alkaline phosphatase , either of which can be elevated because of bone metastasis. But this can also be due to other conditions. Blood tests alone cant confirm metastatic breast cancer in bones or pinpoint the location.
Sometimes, an X-ray can reveal bone metastasis. But other times, your doctor may order one or more of the following imaging tests to look for signs that cancer has reached bone:
Breast cancer isnt a single disease, but a group of diseases. So, treatment is personalized to reflect your:
- specific type of breast cancer
- extent of metastasis
- age and overall health
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Whats The Outlook For Metastatic Breast Cancer
The right treatment plan can improve survival for people with metastatic breast cancer. However, survival rates vary and are dependent on a number of factors including type/biology of the breast cancer, parts of the body involved and individual characteristics. About 1 in 3 women live at least five years after diagnosis. Some live 10 years or longer. Your care team will discuss your prognosis with you in more detail.
Breast Cancer: Why Metastasis Spreads To The Bone
- Date:
- Université de Genève
- Summary:
- When cancer cells break away from a primary tumor and migrate to other organs, this is called ‘metastatic cancer.’ The organs affected by these metastases, however, depend in part on their tissue of origin. In the case of breast cancer, they usually form in the bones.
When cancer cells break away from a primary tumor and migrate to other organs, this is called “metastatic cancer.” The organs affected by these metastases, however, depend in part on their tissue of origin. In the case of breast cancer, they usually form in the bones. In an attempt to identify what determines the organs affected by metastasis, a team from the University of Geneva , in collaboration with researchers from ETH Zurich, has identified a protein involved in this phenomenon. This discovery could lead to the development of therapeutic approaches to suppress metastasis. This work can be read in the journal Nature Communications.
From the primary site of a tumor, cancer cells can invade their microenvironment and then circulate via blood and lymphatic vessels to distant healthy tissue to form metastases. In the case of metastatic breast cancer, the cancer cells primarily colonize the bones, but can also be found in other organs such as the liver, lungs or brain.
Plasticity of tumor cells
Directing metastasis to bone
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Living With Metastatic Breast Cancer
It can be upsetting for you, your family, and other loved ones to learn that breast cancer has spread to other areas of the body. But there are ways to manage your feelings, get support, figure out how to talk about the diagnosis with family and friends, and work after being diagnosed.
Its not always easy to balance your sexual needs with the physical and emotional challenges of a metastatic breast cancer diagnosis. You can manage the sexual issues that can often come up with a metastatic breast cancer diagnosis.
Medications For Mild Bone Pain
Bone pain often responds to heat, or to mild pain relievers such as ibuprofen , naproxen or acetaminophen .
Although you can get these medications without a prescription, check with your health care provider before taking them. For example, if you have a low platelet count, or your kidneys are not functioning normally, or you have heart failure, your health care provider may advise you not to take ibuprofen or naproxen.
Learn more about these medications in metastatic breast cancer care.
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The Benefits Of Diet And Exercise
A diet rich in calcium and vitamin D can also aid in preventing or slowing bone loss in women with breast cancer. Good sources of calcium include dairy products and leafy greens, but inadequate amounts of the mineral from food may require that women take a calcium and/or vitamin D supplement.
Finleys treatment plan includes a calcium supplement taken twice a day. Still, the ongoing bone pain and stiffness from both the cancer and the treatments can be very uncomfortable. Finley said its difficult to sit down for a normal television show or sleep in the same position for too long. You feel like a rusty skeleton, she said.
In the past, some doctors were more hesitant to recommend exercise for bone metastasis because of weakened bones. But a 2021 study confirmed that exercise in a supervised setting is safe for women with metastatic breast cancer, and regular exercise helps improve physical function.