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How Does Breast Cancer Metastasis To The Brain

Characteristics Of Metastatic Brain Tumors Of Breast Cancer

Breast Cancer Metastasis, When Can It Happen?

MRI is one of the most reliable modalities with which to evaluate metastatic brain tumors, although very few studies in the literature have reported the relationships between MRI features and the histology of tumors. Yeh et al. retrospectively analyzed the MRI features of brain metastasis from different subtypes of recurrent breast cancer for subclassification. In that study, the patients were categorized as having luminal type, HER-2-enriched type, or triple-negative breast cancers, and all MRI examinations were performed on a 1.5-Tesla MRI scanner. Both the patients with luminal type cancers and those with HER-2 enriched type cancers showed solid tumors with or without perifocal edema, whereas most patients with triple-negative breast cancers showed distinct features of cystic and necrotic lesions. Brain metastatic lesions frequently show characteristics different from those of the primary tumor histologically and genetically , indicating that MRI is a desirable modality with which to explore the tumor nature of brain metastasis .

H& o Is The Number Of Women Living With Breast Cancer That Has Metastasized To The Brain Increasing

CA We do not know for certain the answer to that question, although our Brain Metastases Specialty Clinic is working with our partners at the Dana-Farber Cancer Institute to examine how the incidence is changing over time. It is logical that the incidence of brain metastases would increase as patients live longer, thanks to medications that work outside of the brain but are unable to reach the brain. For example, trastuzumab is a big, bulky monoclonal antibody that has a difficult time permeating the blood-brain barrier but does an excellent job treating HER2-positive breast cancer elsewhere in the body.

Clinical Trials Involving Tnbcbm

The widespread concern that most drugs are not likely to penetrate the BBB results in the exclusion of patients with breast cancer and other primary tumors from clinical trials.84 This reduces the exposure of BM patients to potentially beneficial novel agents and limits important correlative studies of brain-specific tumor responses. However, new treatment options are urgently needed for TNBCBM patients. In recent years, with a deeper understanding of the molecular changes occurring in TNBC, several promising clinical strategies have emerged, including, among others, treatment with poly adenosine diphosphate-ribose polymerase inhibitors, VEGF inhibitors, and immune checkpoint inhibitors, which are currently under evaluation. Here, we review the completed TNBCBM-related clinical trials and summarize those that are ongoing .

Table 1 Selected Completed Clinical Trials for Triple-Negative Breast Cancer Brain Metastasis

Table 2 Selected Ongoing Clinical Trials for Triple-Negative Breast Cancer Brain Metastasis

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H& O What Are The Sequelae Of Brain Metastases

CA The skull is a confined space, and any additional mass can lead to pressure on the brain and related symptoms. In our clinic, we become concerned about the possibility of brain metastases if patients begin to experience headaches, blurred vision, or unexplained nausea.

The symptoms of brain metastases are highly linked to their location. For example, patients with brain metastases in the frontal lobes tend to exhibit emotional lability and changes in personality. Patients with brain metastases in the parietal lobes tend to have difficulty with speech, movement, and sensation in the extremities. Those with brain metastases in the cerebellum can have gait disturbances and difficulty with coordination. Difficulty with vision can occur with brain metastases in the occipital lobes.

Systemic Treatments For Stage Iv Breast Cancer

Schematics of the process of metastasis. (a) Formation ...

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 and the HER2 status of the cancer:

Hormone receptor-positive cancers

Women with hormone receptor-positive cancers are often treated first with hormone therapy . This may be combined with a targeted drug such as a CDK4/6 inhibitor, everolimus or a PI3K inhibitor.

Women who havent yet gone through menopause are often treated with tamoxifen or with medicines that keep the ovaries from making hormones along with other drugs. Because hormone therapy can take months to work, chemo is often the first treatment for patients with serious problems from their cancer spread, such as breathing problems.

Hormone receptor-negative cancers

Chemo is the main treatment for women with hormone receptor-negative cancers, because hormone therapy isnt helpful for these cancers.

HER2-positive cancers

Trastuzumab may help women with HER2-positive cancers live longer if its given along with chemo or with other medications such as hormonal therapy or other anti-HER2 drugs. Pertuzumab , another targeted drug, might be added as well. Other options might include targeted drugs such as lapatinib or ado-trastuzumab emtansine .

HER2-negative cancers in women with a BRCA gene mutation

HER2-negative breast cancers in women with a PIK3CA mutation

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The Bloodtumor Barrier In Bm

Similar to the BBB, the presence of the BTB also limits the access of potentially effective drugs to BM. The excessive production of proangiogenic factors in metastatic tumors, such as BM from breast cancer or other cancers, stimulates abnormal angiogenesis, resulting in a vasculature characterized by the presence of fenestrated vessels that increase paracellular permeability, referred to as the BTB .49 In contrast to the normal BBB, the BTB is leaky and tends to allow the extravasation of lager molecules.50 However, BTB permeability exhibits clear heterogeneity, both within lesions and among the BMs of different breast cancer subtypes. High expression of the pericyte protein desmin was shown to be correlated with the increased permeability of the BTB, indicative of the involvement of vascular remodeling.51

H& o Could You Talk More About The Brain Metastases Specialty Clinic At Your Institution

CA Managing care for patients with brain metastases is very difficult, which is why we set up a coordinated, multidisciplinary clinic. These patients have issues that need to be addressed quickly by physicians in multiple specialties, including radiation oncology, neurosurgery, and medical oncology. Having the clinic means that patients do not have to wait a week for an appointment with a particular specialist, or travel throughout the hospital or to different locations to address their concernssomething that can pose a particular challenge for someone in fragile health. I would encourage other hospitals to set up similar clinics we spelled out our approach in the piece with Megan McKee as the first author.

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Survival Rates For Metastatic Breast Cancer

According to the American Cancer Society , the 5-year survival rate after diagnosis for people with stage 4 breast cancer is 28 percent. This percentage is considerably lower than earlier stages. For all stages, the overall 5-year survival rate is 90 percent.

Because survival rates are higher in the early stages of breast cancer, early diagnosis and treatment is crucial. But remember: The right treatment for stage 4 breast cancer can improve quality of life and longevity.

How Does Cancer Spread Or Metastasize

Brain metastases developed from HER2 postive and triple negative breast cancer

The spread of cancer usually happens through one or more of the following steps:

  • Cancer cells invade nearby healthy cells. When the healthy cell is taken over, it too can replicate more abnormal cells.
  • Cancer cells penetrate into the circulatory or lymph system. Cancer cells travel through the walls of nearby lymph vessels or blood vessels.
  • Migration through circulation. Cancer cells are carried by the lymph system and the bloodstream to other parts of the body.
  • Cancer cells lodge in capillaries. Cancer cells stop moving as they are lodged in capillaries at a distant location and divide and migrate into the surrounding tissue.
  • New small tumors grow. Cancer cells form small tumors at the new location

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Oncolytic Virus Therapy And Gene Therapy

Oncolytic virus therapy has been described as a prospective treatment option that selectively targets cancer. Various types of oncolytic viruses have been engineered to increase the effectiveness of this treatment and have been shown to improve the therapeutic effect in preclinical research . We have also evaluated combination therapy with genetically engineered oncolytic viruses and systemic treatments such as molecular targeting drugs in mouse glioma models . Administration of talimogene laherparepvec into the tumor improved the durable response rates in a randomized phase III clinical trial , for which the FDA approved the use of this oncolytic virus for patients with recurrent melanoma. Moreover, phase I and II trials of HF10 in patients with malignant tumors, including recurrent metastatic breast carcinoma, have been successfully conducted . Although no oncolytic viruses have been approved for the treatment of brain tumors, we are now starting a phase I/II study evaluating the safety and effectiveness of Ad-SGE-REIC in patients with recurrent malignant glioma as gene therapy. Several recent reports have shown the effectiveness of oncolytic viruses against brain metastasis in preclinical models . Therefore, oncolytic viruses and gene therapy can be a clinically applicable therapeutic platform to target metastatic brain tumors from breast cancer.

Figure 2in vitroin vivoet al

Resection Of Cystic Tumors

Cystic brain metastasis of breast cancer is associated with a poor prognosis . In the surgical treatment of cystic tumors, entire removal of the cyst wall is necessary to achieve GTR because of the higher risk of leptomeningeal dissemination . Cyst puncture is sometimes performed to decompress the tumor during surgery, but the boundary between the tumor and the surrounding brain tissue becomes indistinct by cyst shrinkage. Tomita et al. introduced a technique for visualization of the inner cyst wall by injection of pyoktanin blue solution diluted in 0.3% saline. Although tumor dissemination is a potential concern when performing cyst puncture, solidification with fibrin glue might prevent dissemination and enable easier dissection of the tumor from the surrounding brain tissue .

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One New Therapy Recently Approved Others On The Horizon

Cancer De Higado Metastasis

byJeff Minerd, Contributing Writer, MedPage Today December 16, 2020

Brain metastases are one of the most common and difficult-to-treat occurrences in metastatic breast cancer. They are found in 10% to 30% of patients. In patients with HER2-positive breast cancer, the rate of brain metastases is even higher — up to 50%.

Initial treatments for brain metastases include locally directed therapy with surgical resection, stereotactic radiosurgery, and/or whole-brain radiation therapy. Unfortunately, the rate of intracranial progression with these therapies is high. Even more problematic, most systemic therapies have limited efficacy due to their inability to pass through the blood-brain barrier.

“As patients live longer, they remain at risk for additional episodes of CNS progression and/or new CNS metastases,” Nancy Lin, MD, of the Dana-Farber Cancer Institute in Boston, told MedPage Today. “While radiation therapy can be effective, we don’t have as robust data on many systemic therapy options and very much need to develop new and better systemic options for treatment of brain metastases.”

One new therapy became available in April 2020. The FDA approved tucatinib , in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Drugs Being Investigated

Disclosures

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H& o Are We Getting Any Better At Preventing Brain Metastases

CA We do not have any agents that have been shown to prevent brain metastases. As we get better at treating extracranial metastases and preventing breast cancer from entering the lymphatic system, however, the likelihood that breast cancer will reach the central nervous system decreases. We are seeing significant advances in immunotherapy and molecularly targeted therapy in both melanoma and lung cancer, so that holds true for other solid tumors as well.

H& o How Common Are Brain Metastases

CA Lung cancer, melanoma, and breast cancer are the 3 types of cancers that are most likely to metastasize to the brain. Other solid-tumor cancers and some hematologic malignancies also can metastasize to the brain, but this occurs much less frequently. Brain metastases are common enough in advanced lung cancer that we order magnetic resonance imaging of the brain at initial presentation, whereas we proceed with intracranial imaging in advanced breast cancer only if patients have symptoms that are suggestive of brain metastases.

Across all subtypes, approximately 10% to 15% of women with metastatic breast cancer develop brain metastases. This rate is as high as 30% for women with advanced human epidermal growth factor receptor 2 -positive disease, and as high as 50% for women with metastatic triple-negative breast cancer.

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Clinical Trials For New Treatments

Researchers are always finding new ways to treat metastatic brain tumors. These new methods are tested in clinical trials. Talk with your health care provider to find out if there are any clinical trials you should consider.

Johns Hopkins Comprehensive Brain Tumor Center

Every metastatic brain tumor, and every patient, is different. The specialists at Johns Hopkins take the time to determine which treatment or combination of treatments will be the most effective for you.

Indications For Surgical Treatment

Spying On Breast Cancer Metastasis

Surgical resection continues to play an important role in patients with a limited number of brain metastases and a relatively good performance status. In the early 1990s, three randomized trials on single brain metastasis were conducted to evaluate the efficacy of surgical resection followed by whole-brain radiation therapy compared with whole-brain radiation therapy alone, and the data indicated that surgical resection significantly prolonged overall survival in patients without active systemic disease and with a higher Karnofsky performance status . According to the JCOG0504 trial, surgical resection followed by salvage stereotactic radiosurgery has been established as a standard therapy for patients with fewer brain metastases . SRS is also the effective alternative to surgical treatment for a single metastasis , but the higher doses of SRS increase the risk of the late effect of radiation necrosis . In addition, brain edema caused by metastatic brain tumors resolves significantly faster after surgical resection than after SRS . Moreover, in patients with neurological symptoms caused by brain lesions of > 3 cm with a mass effect or associated hydrocephalus, surgical resection can immediately alleviate these symptoms . Instead, surgical resection followed by SRS can be considered as standard treatment in patients with a few brain metastases, mainly with lesions of > 3 cm in diameter .

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Good News For Patients With Brain Metastases

This post is available in: Spanish

When cancer spreads to the brainfrom a different part of the body, historically life expectancy has beengenerally poor. In addition, its been difficult for doctors to predictsurvivability. But thanks to groundbreaking work in a three-country study thatincluded MiamiCancer Institute, all of that is changing.

Doctors at the Institute, along with those at 17 other cancer centers in the United States, Canada and Japan, have determined that survival rates for patients with brain metastases are improving, making many eligible for clinical trials and innovative treatments that they would have been previously excluded from. In addition, the researchers developed an algorithm that very accurately predicts prognosis.

Weve found that there are subcategories of patients who have substantially better survival were talking survival in years compared to months, said Minesh Mehta, M.D., deputy director and chief of radiation oncology at Miami Cancer Institute. No longer does one need to speculate or guess to make a prediction on a brain metastases patients survival.

If we recognize that thesepatients can have better survival and enroll them on these trials, we might infact identify newer agents that are more effective, Dr. Mehta said.

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Spotting Breast Cancer’s Spread To The Brain Before Symptoms Start Could Improve Survival

Breast cancer patients whose disease has spread to their brains fare better if their metastases are picked up before they begin to cause symptoms, according to a study presented at the 12th European Breast Cancer Conference.

Breast cancer that spreads to the brain is becoming more common and it is one reason why the disease becomes untreatable. However, asymptomatic brain metastases can be identified with an MRI scan and the new research suggests that doing so could mean less aggressive treatment and a longer survival time.

Patients with other forms of cancer that tend to spread to the brain, such as lung cancer, are already given a brain scan when they are first diagnosed. The researchers say a clinical trial of brain scans for breast cancer patients who are at high risk for developing brain metastases is warranted.

The researchers investigated a group of 2,589 German patients who were diagnosed with breast cancer that had already spread to their brains between 2000 and 2019. Of these, 2,009 patients had already experienced symptoms of brain metastases , while the remaining 580 women had no symptoms of brain metastases and were only diagnosed by chance.

When researchers compared the two groups, they found that the women who were asymptomatic were generally fitter, and had fewer and smaller tumors in their brains. They also found that women who were diagnosed with brain metastases before symptoms had developed tended to have less aggressive treatments and to live longer .

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