Sunday, February 25, 2024

Breast Cancer Metastasis Sites Frequency

What You Need To Know

How Cancer Spreads (Metastasis) – Michael Henry, PhD
  • Metastatic breast cancer is serious, but the diagnosis does not always mean the end of life.
  • The most common place for breast cancer to spread is to the bones. The liver and the lungs are other areas where breast cancer can metastasize.
  • In about 15% of cases, metastatic breast cancer can be detected at the time of diagnosis. It can affect people who had breast cancer without seeking treatments, patients with aggressive breast cancer types and those with breast cancer not detected by screening.

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.

How Is Metastatic Breast Cancer Diagnosed

Several tests are used to confirm a diagnosis of metastatic breast cancer. These include:

  • Blood tests: In these tests, a sample of blood is taken from a vein in your arm. Some common blood tests that may be ordered include a complete blood count and a metabolic panel. Your doctor may also order tests for breast cancer tumor markers.
  • Imaging tests: Imaging tests allow your doctor to see whats going on inside of your body and check for the presence of suspicious areas. Some examples of imaging tests that may be used include:
  • Tissue biopsy: If imaging shows a suspicious area, your doctor will take a biopsy from that area to be analyzed in a laboratory. The results of a tissue biopsy can confirm a diagnosis of metastatic breast cancer.
  • The tests that are used as a part of the diagnostic process can vary based on where the cancer has spread to. For example, imaging like a bone scan would be used to check for a bone metastasis while a head MRI would be used to check for a brain metastasis.

    Similarly, additional tests may be used as well, based off of the site. An example of this is bronchoscopy to check for signs of cancer in the airways when a lung metastasis is suspected.

    There isnt a cure for metastatic breast cancer. However, there are treatments aimed at preventing further progression, reducing symptoms, and improving the quality and length of life.

    Treatments are highly individualized. Whats recommended can depend on things like:

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    Tamoxifen And Other Anti

    This section needs expansion. You can help by adding to it.

    For estrogen-receptor-positive metastatic breast carcinoma the first line of therapy is often tamoxifen or another anti-estrogen drug unless there are liver metastases, significant lung involvement, rapidly progressive disease or severe symptoms requiring immediate palliation.

    Symptoms Of Metastatic Breast Cancer

    Figure 4 from Organotropism of Breast Cancer Metastasis

    Symptoms depend on where the cancer has metastasized. According to Habibi, common areas include the bones of the spine, the lungs and the liver. The symptoms can be back pain, shortness of breath, cough and fatigue.

    Some types, including triple negative breast cancer, can also spread to the brain. The patient can experience headache, convulsions, changes in mood, and difficulty with speech or field of vision, Habibi says.

    People who have been treated for breast cancer should be on the lookout for symptoms such as:

    • Back or neck pain

    Reporting these symptoms is important, says Habibi. Patients are usually the first and best people to notice something is not right, and can ask for guidance from their physicians.

    After completion of the active phase of cancer care, and in the absence of specific symptoms, we usually do not recommend routine metastatic workup.

    Doing a lot of unnecessary testing can harm the patient, he explains. Small abnormalities in one test can lead to additional test and biopsies, which can be very stressful to the patient, and repeated testing without symptoms has not been shown to improve outcomes.

    However, patients should continue with their routine follow-ups as prescribed by their surgeon, medical oncologist and primary care doctor, the latter of whom plays a very important role in the survivorship phase.

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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.

    What Causes Metastatic Breast Cancer And Whos At Risk

    Metastatic breast cancer happens when cancer cells break away from the original tumor site. These cells then make their way to other parts of the body via the circulatory or lymphatic systems.

    Once the cells settle somewhere in the body, they have the potential to form a new tumor. This can happen quickly or develop years after initial treatment.

    Anyone thats been diagnosed with breast cancer can go on to develop metastatic breast cancer. Generally speaking, some of the factors below may increase the likelihood of breast cancer metastasizing:

    • having a more aggressive type of breast cancer like triple-negative breast cancer
    • being diagnosed with breast cancer thats at a later stage, such as cancer thats already spread to nearby lymph nodes or the chest wall
    • having a cancer thats growing quickly

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    Comparison Of Survival Among Single Site And Multiple Sites Metastatic Breast Cancer Patients

    We used Kaplan-Meier analysis to compare the effects of single and multiple distant metastatic organs on survival time among the study population. The 1-year and 2-year survival rate and MST were also calculated for each group. The results suggested that there were significant differences among patients with different specific metastatic sites in OS and BCSS . Patients with bone metastasis only had superior survival compared to other metastatic patients . Patients with lung or liver invasion only had similar intermediate MST . However, brain metastasis only group and multiple sites metastasis group had the poorest prognosis compared to other groups and there was no significant difference between these two groups both in OS and BCSS as well. The prognosis of three age groups with single metastasis was also analysed . The results suggested that the prognosis become worse with the increase of age in bone metastasis only and liver only patients , but not in lung metastatic patients . The statistics of brain metastasis was not analysed because of the limited number of samples.

    Figure 3

    Comparison of survival in breast cancer patients with single or multiple metastatic sites. Kaplan Meier analysis for OS and BCSS were shown. The 1-year, 2-year survival rate and median survival time were listed respectively in the table below the graph. MST: median survival time.

    Bone Metastases Within Metastatic Patterns

    Metastatic Breast Cancer

    We evaluated six metastatic sites: bone, liver, lung, brain, lymph nodes , and other anatomical sites.

    For each case, the location of the metastatic lesions and the number of metastatic sites were recorded. In all cases, this constellation was described at the initial diagnosis of DMD . When additional metastatic lesions subsequently developed at other locations, the new metastatic site was described as the second DMD event. As an example, a patient was diagnosed with DMD, consisting of bone and liver metastases, in June 2005. This was recorded as two metastatic sites at the first DMD event. Palliative therapy was initiated. In August 2007, the disease progressed and additional lung metastases were found. This was recorded as one site for the second DMD event. In this particular case, we recorded two DMD events, a total of three metastatic sites and a time of 13 months between the first and second DMD event. When metastatic lesions developed in different locations or regions within an organ or organ system , these were not considered as separate DMD events.

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    How Were Radiotherapy And Surgical Interventions For Bone Metastases Embedded In The Palliative Setting

    For each intervention, we recorded the time to procedure, in months, with respect to the first diagnosis of DMD and the survival time after the procedure. Based on this data, we also calculated in which third of the palliative disease course the procedure had been performed. For example, a patient was diagnosed with DMD, consisting of bone and liver metastases, in June 2005. Eight months later, she received surgery for BM. Eventually, the patient died of metastatic BC in June 2008 . In this particular case, we recorded that the surgical procedure had been performed in the first third of the palliative disease course.

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  • Case 1: brain metastasesCase 1: brain metastasesDrag here to reorder.
  • Case 2: lung metastasesCase 2: lung metastasesDrag here to reorder.
  • Case 3: peritoneal metastasesCase 3: peritoneal metastasesDrag here to reorder.
  • Case 4: bone metastasesCase 4: bone metastasesDrag here to reorder.
  • Case 5: bone metastasis T1Case 5: bone metastasis T1Drag here to reorder.
  • Case 5: bone metastasis T2 FSCase 5: bone metastasis T2 FSDrag here to reorder.
  • Case 6: CPA metastasis T1 C+Case 6: CPA metastasis T1 C+Drag here to reorder.
  • Case 7: brain metastasesCase 7: brain metastasesDrag here to reorder.
  • Case 8: diffuse bony metastasesCase 8: diffuse bony metastasesDrag here to reorder.
  • Case 9Case 9Drag here to reorder.
  • Case 10: lumbar lytic and sclerotic bone metastasisCase 10: lumbar lytic and sclerotic bone metastasisDrag here to reorder.
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    Impact Of Molecular Subtype On Metastatic Sites

    Distribution of molecular subtypes in all breast cancer patients, and in patients with bone, lung, liver, and brain metastases distribution of molecular subtypes in all breast cancer patients and in patients with oligo-organ metastases .

    Abbreviations: met, metastasis HER2, human epidermal growth factor receptor 2 HR, hormone receptor +, denotes positive , denotes negative.

    Metastasis To The Lungs

    Why PDX Are Needed for Metastatic Breast Cancer Research

    Breast cancer cells released from the primary tumour may also spread to the lungs.49 Lung metastasis is usually observed 5 years after initial breast cancer diagnosis, with > 60% mortality rate following lung metastasis.49 The subtype of breast cancer affects the frequency of lung metastasis. Patients with TNBC were reported to be more likely to develop lung metastasis compared to other subtypes.48 The development of lung metastasis in patients with breast cancer may be because of an inherent ability of breast cancer cells to the lungs, or an ability to interact with the lung microenvironment. Premalignant breast cells have been shown to invade the lungs after injection into the blood, suggesting that breast cancer cells may have some intrinsic ability to establish in the lungs.50 It has been shown in vitro that the migration and proliferation of breast cancer cells were stimulated by the conditioned medium of the lungs, suggesting that factors from the lungs promote lung metastasis. One such factor identified was selectin, a cell adhesion molecule.51

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    Metastatic Breast Cancer Treatment

    Metastatic breast cancer can have different presentations for each patient, and can behave differently from one person to the next. But for most, individualized treatment can slow the spread of cancer, lessen the impact of symptoms or both.

    We see patients with a whole host of presentations and degrees of aggressiveness. Were not looking at all metastatic diagnoses with the same lens. When planning treatment and supportive care, we look at each individual patient and consider all aspects of their health and well-being.

    The mainstay of therapy in the setting of metastatic disease is systemic therapy, Habibi explains.

    Systemic therapies use medicines, and may include:

    Local therapy: Examples of this approach include surgery and radiation directed at one or more specific spots where breast cancer has spread. Local therapy can be used to address oligometastatic breast cancer, which is breast cancer that has spread to just one spot or to a limited number of areas.

    If a metastatic area remains stable with treatment, it can be treated as a chronic disease, Habibi says, noting that in these situations, the strategy is preventing the cancer from advancing. For oligometastatic breast cancer, he says that a combination of chemotherapy, radiation treatments or surgery to remove cancerous areas can address symptoms and extend life.

    Regional therapy includes surgery or radiation to treat metastatic cancer in nearby affected lymph nodes.

    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.

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    Whats The Difference Between Metastatic And Recurring Breast Cancer

    Recurrent cancer is cancer that comes back after your initial treatment. This can happen when treatment doesnt completely destroy all of the cancer cells in a tumor. As time passes, these remaining cancer cells can begin to grow into detectable tumors.

    Like metastasis, recurrence can happen with almost every type of cancer. As well see below, some types of recurrent cancer can happen distantly and therefore also fall under the umbrella of metastatic cancer.

    Breast cancer may recur locally, regionally, or distantly:

    • Local recurring breast cancer occurs when a new tumor develops in the breast that was originally affected. If the breast has been removed, the tumor may grow in the chest wall or nearby skin.
    • Regional recurring breast cancer happens in the same region as the original cancer. In the case of breast cancer, this may be the lymph nodes above the collarbone or in the armpit.
    • Distant recurring breast cancer happens when cancer cells travel to a different part of the body. This new location is far away from the original cancer. When cancer recurs distantly, its considered metastatic cancer.

    , the most common metastasis locations for breast cancer are the:

    The frequency that breast cancer metastasizes to each of these sites can vary based off of the population studied. A in Scientific Reports included a group of 4,932 people with metastatic breast cancer. Researchers determined the metastatic site for each person and found that:

    Radiotherapy Analysis: Definition Of Series Volumina And Anatomic Sites

    Metastasis– Molecular Basis

    For each case, the number of radiotherapeutic interventions , their irradiated planning target volumes and the corresponding osseous metastatic sites were recorded. For example, a patient received radiotherapy for BM in June 2005. In this first treatment series, two PTV were irradiated: the humerus with 15 Gy and a section of the thoracic and lumbar spine with 30 Gy. In a second series in January 2006, the brain and two further bone volumes right femur and a segment of the cervical and thoracic spine were irradiated. In this particular case, we recorded two radiotherapy series, five PTV and a total of seven anatomic sites .

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    Symptoms Of Metastasis May Vary Depending On Where The Cancer Has Spread To

    Here are some symptoms that vary by locations commonly associated with breast cancer metastasis.

    Metastasis in the bone may cause:

    • Severe, progressive pain
    • Bones that are more easily fractured or broken

    Metastasis to the brain may cause:

    • Persistent, progressively worsening headache or pressure to the head
    • Vision disturbances
    • Behavioral changes or personality changes

    Metastasis to the liver may cause:

    • Abnormally high enzymes in the liver
    • Abdominal pain, appetite loss, nausea, and vomiting

    Metastasis to the lungs may cause:

    • Chronic cough or inability to get a full breath
    • Abnormal chest X-ray
    • Other nonspecific systemic symptoms of metastatic breast cancer can include fatigue, weight loss, and poor appetite, but its important to remember these can also be caused by medication or depression.

    If you notice these symptoms, be sure you talk with your physician. They could be important for getting the treatment you need.

    Materials on this page courtesy of National Cancer Institute

    Staging Of Breast Cancer For Metastatic Disease

    The most common staging system for breast cancer is the American Joint Committee on Cancer TNM , which is based on tumour size and the degree of locoregional invasion by the primary tumour , the extent of regional lymph node involvement and presence of distant metastases . M1 indicates the presence of any metastases to distant organs, implying a stage IV disease . Breast cancer may be stage IV at first diagnosis, or it can be recurrent from previous breast cancer. Stage IV disease showed a 5-year survival rate of approximately 22%, although this rate varies according to other factors, such as the hormone receptor status . The median survival for patients with breast cancer and bone metastases is 65months in the oestrogen/progesterone-receptor-positive groups, and 40months in both the human epidermal growth factor receptor 2 positive and triple-negative group .

    Table 1 Breast cancer staging

    Multi-modality imaging is widely used clinically for disease staging. However, all cancers are potentially systemic diseases and whole-body imaging techniques, such as whole-body hybrid imaging or whole-body magnetic resonance imaging are increasingly performed to reflect this.

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    Preferred Sites For Breast Cancer Metastasis

    The draining, or sentinel, lymph node in the axilla, which is located in close proximity to the breast tumour site, is usually the first site of metastasis.42 Breast cancer then spreads to distal sites, most frequently bone, lungs, liver, and the brain.43 Estimates from a recent study showed that at the time of diagnosis, patients with metastatic breast cancer were found to most frequently present with bone metastasis , followed by lung and liver metastasis, while the brain was the least common site for metastasis .44

    The Process Of Metastasis


    The step one of the metastasis is that tumor cells break away from the tumor bed and migrate from the stroma into the bloodstream . In order to leave the primary tumor and invade surrounding tissues, these tumor cells need to reduce their tight cell adhesion through undergoing epithelial-mesenchymal transitions . EMT is typified by loss of epithelial traits and acquisition of mesenchymal traits to increase the mobility of tumor cells. EMT also links to cancer metastasis with stem cell properties . Moreover, the integrin-mediated adhesion and debonding interactions with matrix components is critical for regional migration. And the intratumoral blood vessels characterized by increased permeability allow cancer cells to enter the systemic circulation readily .

    Adjusting to new environment is another hurdle for circulating tumor cells to form metastasis. Disseminated cancer cells will spring up in targeted tissues and organs through a way that is significantly different from their origins. Cancer cells must acquire new capabilities, especially the ability to interact with cells in the ECM and new microenvironment. Tumor cells form a two-way connection with circumferent stroma in the early stage of invasion and after that, tumor-stroma interaction helps the tumor to develop toward metastasis .

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