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.
Getting Back On Track: How Bone Metastases Are Treated
Oncologists have a range of tools that can help alleviate the pain and discomfort of bone metastases as well as treat the cancer itself, including:
Other ways to effectively manage pain and discomfort from bone metastases include using hot and cold compresses practicing relaxation methods like meditation, physical therapy, or yoga and doing other gentle forms of exercise. Ask your health care team about programs that can help keep you safely active. Strong muscles protect bones, stresses Huston, and being active makes you feel better both physically and psychologically.
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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What Are The Symptoms Of Bone Metastases
Symptoms of bone metastases can vary depending on how much the cancer has spread and which bones are affected. Some common signs and symptoms include:
- Bone fractures. Damage to bones makes them weak and more prone to fractures or bone breaks. Sometimes this is the first sign that cancer has spread to the bones.
- Bone pain. This is the most common symptom of bone metastases. The pain may be dull and achy or sharp with a sudden onset.
- Nerve issues. If a bone tumor is pressing on the spinal cord, it can affect nerve function. Known as spinal cord compression, this can lead to symptoms like tingling, weakness, or numbness in the legs or arms. Left untreated, it can lead to paralysis.
- High calcium levels in the blood. Also known as hypercalcemia, this can lead to symptoms like constipation, extreme thirst, low appetite, or confusion. It can typically be found through blood work.
- Anemia. When bones are affected, it can reduce the number of blood cells created by bone marrow. This lowers red blood cells in the blood, known as anemia.
If you live with cancer, your care team will monitor any changes in your health. Its important to be aware of any signs that may indicate that your cancer has spread to the bones. Its always best to catch bone mets early to help slow the spread.
The Importance Of Osteoblasts In Osteolytic Breast Cancer Metastasis
Just as osteoblasts are a critical partner in normal bone remodeling, they are vital to the metastatic osteolytic process. Because osteoblasts secrete both RANKL and OPG, they are major mediators of osteoclastogenesis . Current therapies consist of blocking osteoclast activity as a means of disrupting the vicious cycle. Bisphosphonates such as zoledronic acid bind to hydroxyapatite of the bone matrix and are ingested by osteoclasts, which then undergo apoptosis. However, this approach has not entirely solved the problem. Administration of bisphosphonates may slow osteolytic lesion progression and stabilize or increase overall bone density, but does not bring about healing . There is evidence in both humans and animals that bone loss in osteolytic metastasis is partly due to the failure of the osteoblasts to produce new osteoid for the bone matrix.
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Managing Your Feelings About Metastatic Breast Cancer
Regardless of whether metastatic breast cancer is a first diagnosis or a recurrence, its normal for people to feel angry, scared, stressed, outraged, depressed, or calm. You may question the treatments youve had, feel mad at your doctors, or be prepared to deal with the diagnosis in a matter-of-fact way. There is no right or wrong way to come to terms with a metastatic breast cancer diagnosis.
Many people find it helps to concentrate on understanding the diagnosis, learning all they can about different treatment options, and taking the time to get second opinions. Information can give people a feeling of control, which can help them manage any fears they may have.
Loss of control is a huge issue for women diagnosed with metastatic breast cancer, said Musa Mayer, author of Advanced Breast Cancer: A Guide to Living with Metastatic Disease and patient advocate. The process of gathering information and learning about the disease and treatment can be very stabilizing and help women feel more in control.
Some people with metastatic breast cancer may feel the urge to withdraw from social connection. But in interviews and publications, many people who are living with metastatic breast cancer have said that distancing themselves from loved ones wasnt very helpful in dealing with their diagnosis.
Still, its important to remember that everyone deals with fear and stress differently. Coming to terms with the diagnosis takes time and is different for everyone.
Diagnosing Metastatic Breast Cancer
To diagnose metastatic breast cancer, your doctor may recommend one or more tests:
Blood Tests
- A complete blood count to assess your bone marrow function
- Tests for minerals and enzymes that can provide evidence of spreading cancer or other health conditions
- Tests for proteins that signal the presence of cancer
Imaging Tests
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Emotional And Spiritual Care
End-of-life care also includes emotional, mental, and spiritual therapy. A personâs healthcare team may include social workers, counselors, mental health professionals, and religious or spiritual advisors.
According to the Anxiety and Depression Association of America, up to 40 percent of people with cancer experience serious mental distress. This may include anxiety, depression, panic attacks, and post-traumatic stress disorder .
Medications, therapy, religious or spiritual rituals, and support groups can help a person cope with mental health issues and stress during this difficult time.
Caregivers may also need help with stress, anxiety, and depression. The palliative care team can usually also provide support and advice to caregivers for their emotional needs.
The Breast Cancer Healthline app provides people with access to an online breast cancer community, where users can connect with others and gain advice and support through group discussions.
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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When Cancer Goes Beyond Your Breast
If your doctor told you that your breast cancer has spread to other parts of your body, it’s at a more advanced stage than if it’s only in your breasts. How far it has spread is one of the things your doctor will consider when they tell you the “stage” of your cancer. It’s considered “metastatic” if it has spread far from your breasts. Every case is different. For some women, it becomes something they live with for a long time. For others, focusing on pain management and quality of life is the main goal.
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Consider A Clinical Trial
Doctors and scientists continue to research new approaches for treating cancer, including brain metastases. These new approaches are tested in clinical trials.
If youre interested in trying an experimental treatment option, talk with your oncology care teamabout clinical trials that you may be eligible for. You can also find a searchable database of NCI-supported clinical trials
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Bone Weakening And Fracture
Secondary breast cancer in the bone may mean the affected bones are weakened, which can increase the risk of a fracture.
If a bone has fractured you may need surgery to try to repair the fracture. You may also be given drug treatment to stop this happening in the future. You may have radiotherapy after the surgery.
Cancer Associated Fibroblasts In Breast Cancer Metastasis
As discussed in the previous sections, osteoblasts that originate from MSCs are increasingly recognized as therapeutic targets for breast cancer bone metastasis . Another mesenchymal-derived, endosteal niche cell type with a potential to regulate the establishment and progression of bone metastasis includes fibroblasts. Although usually quiescent in normal tissue, fibroblasts acquire an activated phenotype during processes such as wound healing, tissue inflammation or fibrosis. Given the physiological role of fibroblasts, their involvement in tumor growth is apparent as cancers are considered as wounds that do not heal . Cancer-associated fibroblasts , activated fibroblasts that are associated with cancer, are one of the most abundant stromal cell types in breast cancer and are associated with poor prognosis .
The contribution of CAFs in cancer progression has been extensively reviewed elsewhere . Briefly CAFs produce growth factors that contribute to disease establishment , TGF-, SDF-1, VEGF, IL-6) in addition to MMPs. All of these factors are well-known to affect several hallmarks of cancer . Whereas, the contribution of CAFs to primary tumor growth is intensely investigated and defined, the origin and role of CAFs in the metastatic environment, especially in breast cancer bone metastasis, remain poorly defined . Within the next chapters we discuss evidence that supports a role of CAFs during the progression and establishment of breast cancer bone metastasis.
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Bone Metastases And Bone Problems
People with bone metastases are at risk of serious bone complications such as bone fractures , spinal cord compression and bone pain.
Bone complications are a concern for people with bone metastases as they can cause pain and may lead to loss of mobility, impacting quality of life. Bone complications can also decrease survival . With the use of bone-strengthening drugs, bone complications are not common .
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.
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How Is Metastatic Breast Cancer Treated
The main treatment for metastatic breast cancer is systemic therapy. These therapies treat the entire body. Systemic treatments may include a combination of:
Your care team will plan your treatment based on:
- Body parts cancer has reached.
- Past breast cancer treatments.
- Tumor biology, or how the cancer cells look and behave.
Whats The Life Expectancy With Metastatic Breast Cancer In Bones
Metastatic breast cancer in the bones is not curable, and the prognosis typically isn’t as positive as earlier-stage cancers. Per the ACS, the five-year relative survival rate of a personal with distant breast cancer is 28%. That means that people with metastatic breast cancer are about 28% as likely to be alive five years after diagnosis as people who don’t have that cancer.
However, data shows that metastatic breast cancer in the bones seems to have the best survival rate compared to other types of metastatic breast cancer. A 2019 study published in the journal BMC Cancer looked at five years of data to track the survival rates of stage four breast cancer patients and calculated specific rates based on the site of metastasis. The researchers found that patients with bone metastasis had the best overall survival rate of 50.5% after three years. This means that 50.5% of patients were still alive three years after diagnosis.
Other research has estimated that the one-year survival rate of metastatic breast cancer in the bones is 51% and the five-year survival rate is 13%.
But these numbers are estimates, not foregone conclusions. A lot of factors can impact a person’s prognosis, says Dr. Lin, including the type of cancer they have, where it spread, how old they are, and any other pre-existing conditions or health problems they have. And some cancers respond better to treatment than others, which absolutely affects a person’s survival.
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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 .
Treatments For Lung Metastasis
Metastatic breast cancer in any part of the body is usually treated with systemic medicines, which treat cancer throughout the entire body. For lung metastasis, local treatments that specifically target the lungs, such as surgery or radiation, are sometimes recommended. But most lung metastases dont require local treatments because they dont cause major symptoms.
Chemotherapy destroys or damages cancer cells as much as possible and, therefore, doctors recommend it as a treatment for metastatic breast cancer. Because chemotherapy medicines are systemic treatments meaning they affect the entire body doctors generally recommend chemotherapy if:
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the cancer is growing quickly
Doctors often combine chemotherapy with targeted therapies, which are medicines that target specific characteristics of cancer cells.
Each persons chemotherapy treatment plan is different. But there are some general guidelines that doctors follow when using chemotherapy to treat metastatic breast cancer:
If breast cancer comes back after chemotherapy or doesnt respond to chemotherapy medicines, you can try a different combination of medicines. There are many chemotherapy medicines, and if one medicine or combination of medicines doesnt work, there is almost always something else you can try.
Learn more about Hormonal Therapy.
Learn more about targeted therapies used to treat metastatic breast cancer.
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Can Stage 4 Breast Cancer Go Into Remission
Stage 4 breast cancer can go into remission, meaning that it isnt detected in imaging or other tests. Pathological complete remission indicates a lack of cancer cells in tissues removed after surgery or biopsy.
But its rare to take tissue samples while treating stage 4 breast cancer. This could mean that although treatment has been effective, it hasnt completely destroyed the cancer.
Advances in stage 4 breast cancer treatments are helping to increase the length of remission.
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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Working After A Metastatic Breast Cancer Diagnosis
The effect of a diagnosis of metastatic breast cancer on work life is different for every person. You may have an understanding supervisor, a flexible schedule, and an encouraging team to support you. Or you may have questions about how best to manage treatment and work. Some women may wonder if they should be working at all. Others may feel the need to work because theyre concerned about paying for treatment.
In working with people living with stage IV disease, theres a constant conversation and struggle about whether to work or not, says Rosalind Kleban, licensed clinical social worker who serves as administrative supervisor for psychosocial programs and Memorial Sloan-Kettering Evelyn H. Lauder Breast Center in New York City. Part of the discussion that leans toward working is that it very often acts as a distraction, a way to be involved in things and people outside of the illness. I think that both sides of the equation should be looked at very seriously because work has some value for all of us including people with an illness.
Ultimately you have to do what is right for you, your lifestyle, and your family. There is no one best way to manage the emotional, physical, and legal aspects of balancing your job and your treatment.
Learn more general information about breast cancer and your job.
Read more specific information about working with metastatic breast cancer: