Hepatic Resection For Isolated Breast Cancer Liver Metastasis: A Single
1Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
2Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
Primary Tumor Growth And Metastasis Detection In Vivo
Specific pathogen free nude mice were purchased from the Vital River Laboratory Animal Technology Co. Ltd . MDA-231 cells were subcutaneously transplanted. After the formation of primary tumors , the mice were randomly grouped and different doses of PTX were diluted with normal saline and administrated by intraperitoneal injection . After five cycles of treatment, the mice were euthanized. The primary tumor growth and metastatic intensities were then measured, and images were captured. The procedures of animal experiments mentioned in our study were approved by the Animal Care and Welfare Committee of Peking University Health Science Centre. The animal housing facility was in accordance with the guidelines of the national standard Laboratory AnimalsâRequirements of Environment and Housing Facilities . The care of the laboratory animals and the experimental operations were carried out in accordance with the Regulations for the Administration of Laboratory Animals.
A Model For Breast Cancer Liver Metastasis
An increasingly sophisticated understanding of breast cancer liver metastasis is emerging. It appears that BCLM is mainly associated with specific subtypes in patients with breast cancer however, no direct correlation between subtypes and BCLM has been found. By combining the knowledge from the extant research, we propose a model for breast cancer liver metastasis , as follows: intravasation: invasive breast cancer cells invade via the endothelium of a tumor blood vessel into the circulation circulation: breast cancer cells survive in the blood vessels and lack of cell-cell or cell-matrix attachments margination: CTCs arrest at the liver site by adhering to the sinusoidal endothelial cell via specific sets of adhesion molecules, such as cadherins, integrins, Ig-SF, and CD44 extravasation: the migrated breast cancer cells invade through the endothelial wall of sinusoidal endothelial cells, migrates, and finally proliferates in the liver and colonization: breast cancer cells survive and form a life-threatening macrometastatic focus in the liver microenvironment by mediating hypoxia-inducible factor-regulated genes , the status of ER, PR, and HER-2 expression, and angiogenesis for breast cancer cells.
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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Expert Review And References
- Alexander HR Jr, Berlin J, Moeslein F. Metastatic cancer to the liver. DeVita VT Jr, Lawrence TS, Rosenberg SA. Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins 2011: 149:2177-2191.
- BC Cancer Agency . Cancer Management Guidelines: Secondary Neoplasms of the Liver. BC Cancer Agency 2006: .
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Tissue Distribution Of Metastases By Intrinsic Subtype
The seed and soil hypothesis proposes that favorable interactions between the metastatic tumor cell and the organ-specific microenvironment are required for successful expansion of cancer cells in different vital organs . Better understanding the mechanism of this interaction could greatly facilitate the uncoupling of this relationship, thereby effectively preventing and/or treating metastatic disease. Recent studies have examined the relationship between primary tumor characteristics and metastatic dissemination patterns, in order to understand this predilection. A 2011 study examining the maintenance of gene expression signatures between matched primary and metastatic breast cancer samples uncovered that > 90% of genetic signatures found in the primary tumor are maintained in distant metastases . Interestingly, the gene signatures with the highest rate of discordance between primary and metastatic samples were associated with extracellular matrix proteins, which could be a result of a direct influence of the unique ECM itself on gene expression, or simply differing levels of fibroblasts found in primary tumors versus metastases. Overall, these results confirmed that primary breast tumor gene profiles are strong predictors of metastatic behavior.
How Are Liver Metastases Diagnosed
If a liver function test suggests there could be a problem, your doctor may order one or more of these imaging tests:
CT scans to look for signs of cancer in bones, organs, soft tissue, and blood vessels
MRI to view detailed images of soft tissue like the liver
positron emission tomography scans that use a safe, injectable radioactive tracer to spotlight areas that may have cancer
ultrasounds to show organs and blood flow
biopsy of liver tissue to confirm breast cancer spread or liver cancer
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Early Detection Predictive Models And Treatment Of Bclm
Hepatic resection is a rare option for BCLM as the vast majority of patients have bilobar, unresectable disease at diagnosis. This difference in discovery of liver metastasis at a resectable state between CRLM and BCLM could stem from the lack of surveillance recommendations for BCLM. National Comprehensive Cancer Network guidelines recommend follow-up computed tomography of the abdomen and pelvis every 612 months for 5 years in stage II and higher colon cancer. Ninety-three percent of all CRLM were diagnosed within 3 years of the primary . Breast cancer, on the other hand, carries no recommendation for imaging surveillance for liver metastasis. Median time to liver metastasis from all included studies in this review is 41.35 months , comparable to that of CRLM.
This presents a major area of further research, as developing a reliable predictive model for development of liver metastasis based on characteristics at diagnosis of primary disease could pave the way for selective surveillance for liver metastatic disease. This would, in theory, result in earlier diagnosis of BCLM, which could, in turn, broader treatment options and potential survival advantage.
Ongoing Studies In Vivo
Ongoing studies are utilizing in vivo models of BCLM to identify superior systemic and local therapies. The majority of studies focus on liver metastases arising from colorectal cancer. However, these methodologies can be translated to BCLM to some extent. In one study, PDXs were established from sixteen patients with colorectal liver metastases, and mice harboring these PDXs were treated with a variety of chemotherapeutic agents . Of the 16 total PDXs established, 6 were effective in mimicking the derivative patients response to treatment. Of these six PDXs, four demonstrated comparable chemo sensitivity . Another study explored if mechanism of drug delivery could improve patient response. Guo et al. developed a nanoprecipitate from the active forms of folinic acid and oxaliplatin . They found that this nanoprecipitate significantly decreased liver metastases and showed enhanced activity in combination with the anti-PD-L1 antibody. These studies support the use of personalized precision medicine in the treatment of BCLM. Given the livers unique vasculature and metabolic capacity, it is necessary to identify targeted drugs and optimize the drug delivery vehicle to maximize its activity.
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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 or painful wound in the breast
- To treat a small number of metastases in a certain area, such as the brain
- To help prevent or treat bone fractures
- When a cancer is pressing on the spinal cord
- To treat a blood vessel blockage in the liver
- To provide relief of pain or other symptoms anywhere in the body
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 the goalwhether it is to try to cure the cancer or to prevent or treat symptoms.
Role Of Sinusoidal Capillaries
Previous studies have reported that the initial arrest of cancer cells in the sinusoids of the liver is restricted by the sizes of cancer cells . Haier et al. has determined that tumor cells adhere to sinusoidal capillaries, the internal diameter of which is larger than the tumor cells. Unique structural features of liver, including the existence of a fenestrated endothelium and lack of an organized sub-endothelial basement membrane, have a great impact on the interactions between breast cancer cells and the liver microenvironment. Of great interest, the fenestrated endothelium controls liver-specific microvascular exchange and impacts the ability of cells to transmigrate through the vessels into the liver . Moreover, previous studies have revealed that breast cancer cells extend cellular projections through the fenestrated endothelium into the space of Disse on seeding the liver, which makes direct contact with hepatocytes . In addition, Martin et al. has found that breast cancer cells are bound to vessels with clear vascular labeling in the sites of liver metastases. Thus, sinusoidal capillaries play a significant role in the initial arrest of breast cancer.
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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.
When Breast Cancer Spreads To The Liver
Posted: Feb 23, 2021, 7:00:00 AM
Breast cancer can spread months or even years after you stop cancer treatments. Its estimated that 1 in 3 women with breast cancer eventually develops metastatic breast cancer. The condition also affects men with breast cancer. Metastatic breast cancer is also known as stage 4 or advanced breast cancer.
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.
Prognosis For Metastatic Breast Cancer
Metastatic breast cancer isnt the same for everyone who has it. According to the National Breast Cancer Foundation, your symptoms at stage 4 will depend on the degree to which the cancer has spread in your body.
Although metastatic breast cancer has no current cure, it can be treated. Getting the right treatment can increase both your quality of life and longevity.
Life expectancy for breast cancer is based on studies of many people with the condition. These statistics cant predict your personal outcome each persons outlook is different.
The following factors can affect your life expectancy with metastatic breast cancer:
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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.
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.
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Data Extraction And Management
Fifty-one studies were reviewed in full text format. Data was extracted directly from the text of the article and collated into the following categories: study design, type of intervention, total patients, mean age, histology of primary tumor, hormone receptor status of primary tumor, adjuvant therapy, extent of hepatic resection , resection margin status, time from primary to liver metastasis, RECIST response, post-procedure complications, 30-day mortality, median overall survival, disease free survival, 1-, 3-, and 5-year survival. All relevant text, tables, and figures were reviewed for data extraction.
For safety and effectiveness outcomes, overall rates of each complication were calculated using the unweighted median figures given in each study. In studies where a mean was presented when a median value is most commonly used, the data will be provided for table completion, but notation is made to identify the difference in reporting method. Consensus discussion resolved all discrepancies between reviewers.
The Risk Of Metastatic Breast Cancer
The risk of metastasis after breast cancer treatment varies from person to person. It depends on:
- The biology of the tumor
- The stage at the time of the original diagnosis
- The treatments for the original cancer
Modern treatments continue to improve survival for people with metastatic breast cancer. However, survival varies greatly from person to person.
About one-third of women diagnosed with metastatic breast cancer in the U.S. live at least 5 years after diagnosis . Some women may live 10 or more years beyond diagnosis .
Your oncologist can give you some information about your prognosis, but they dont know exactly how long you will live.
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Poor Appetite And Weight Loss
Sometimes people with secondary breast cancer cannot eat as much as usual. This means they may have difficulty maintaining their weight as well as providing the body with energy.
Poor appetite can be due to the effects of the cancer, treatment or anxiety. You might find it easier to eat little and often instead of having set meals. If you still feel youre not eating enough, or are losing weight, talk to your doctor or nurse about dietary supplements or ask to speak to a dietician for specialist advice. In some circumstances you may be prescribed medication to help stimulate your appetite.
Palliative And Supportive Care
Palliative and supportive care focuses on symptom control and support. Its an extremely important part of the care and treatment for many people living with secondary breast cancer and can significantly improve quality of life for them and their families.
People often associate palliative care with end-of-life treatment. However, many people value having it at any stage of their illness, alongside their medical treatment, to help prevent and relieve symptoms such as pain or fatigue. It can also help with the emotional, social and spiritual effects of secondary breast cancer.
The palliative and support care teams are based in hospitals, hospices and the community. You can be referred by your treatment team, GP or breast care nurse depending on your situation.
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Progression During Hormone Therapy
For hormone receptor-positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy sometimes helps. For example, if either letrozole or anastrozole were given, using exemestane, possibly with everolimus , may be an option. Another option might be using fulvestrant or a different aromatase inhibitor, along with a CDK inhibitor. If the cancer has a PIK3CA mutation and has grown while being treated with an aromatase inhibitor, fulvestrant with alpelisib might be considered. If the cancer is no longer responding to any hormone drugs, chemotherapy immunotherapy, or PARP inhibitors might be options depending on specific features of the cancer or any gene changes that might be present.
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.
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Treatment For Liver Metastasis
Metastatic breast cancer in any part of the body is usually treated with systemic medications, which treat cancer throughout the entire body. For liver metastasis, local treatments that specifically target the liver, such as surgery or radiation, are sometimes recommended.
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:
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.
Localized chemotherapy directs chemotherapy medication into liver tumors, avoiding damage to surrounding healthy organs.
There are a couple of local chemotherapy options for liver metastasis:
Learn more about Hormonal Therapy.
Learn more about targeted therapies used to treat metastatic breast cancer.