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By tracking the spread of breast cancer cells in mice, researchers have identified two proteins that may regulate the movement of breast cancer cells into and out of bone marrow.
A protein called E-selectin may allow breast cancer cells to enter certain regions of the bone marrow, and another protein, CXCR4, may help breast cancer cells remain within the bone, according to the study results.
In humans, breast cancer can recur in patients more than a decade after the disease has been treated. Using a technique known as high-resolution, real-time microscopy, the investigators followed the movements of individual breast cancer cells in mice containing human breast cancer cells that metastasize to bone.
The researchers found that breast cancer cells express multiple proteins that may bind to E-selectin.
The cells traveled to specific areas within the bone marrow known as perisinusoidal vascular regions, the researchers found. The researchers then showed that the receptor protein CXCR4 may help to anchor breast cancer cells within the bone marrow. In additional experiments, the researchers used an E-selectin inhibitor, called GMI-1271, to prevent some breast cancer cells circulating in the bloodstream from entering the bone marrow. The researchers will continue to investigate the mechanisms uncovered in this study using the mouse model and tissue from patients with breast cancer.
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. Using the genetic changes in a patient’s tumor to determine their treatment is known as precision medicine. Precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease.
Today, when you are diagnosed with cancer, you usually receive the same treatment as others who have same type and stage of cancer.
The hope of precision medicine is that treatments will one day be tailored to the changes in each person’s cancer.
Though experts believe that precision medicine can become an additional option for people with cancer, it is not likely to replace the cancer treatments we already have. There are drugs that have been proven effective against specific genetic changes in certain cancers and approved by the FDA. Even though researchers are making progress every day, treatment using precision medicine is not yet part of routine care for most patients. If there is a targeted drug approved for your type of cancer, you will likely be tested for a genetic change that might be driving it. If there is not an approved targeted drug for your type of cancer, you still may be tested for genetic changes. If you have a type of cancer with a genetic change that can be treated with an approved drug, testing for genetic changes in your cancer is part of routine care. If you join a precision medicine clinical trial, the cost of testing for genetic changes may be covered by the organization sponsoring the trial.
If there is not an approved targeted drug for your type of cancer and you are not in a clinical trial using precision medicine, your insurance company will probably not cover the costs of having your cancer tested for genetic changes. Testing for genetic changes requires the use of complex technology and requires the services of people with specialized training.
Researchers have not yet discovered all the genetic changes that can cause cancer to develop, grow, and spread.
Once genetic changes are discovered, another active area of research involves looking for drugs that can target these changes, then testing these drugs with people in clinical trials.
Researchers are also working to understand and solve the problem of drug resistance that can limit how well targeted therapies work. Gefitinib, the chain-like structure, bound to the mutated epidermal growth factor receptor.
Last month, the Food and Drug Administration (FDA) approved gefitinib (Iressa®) for the initial treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have specific mutations in the gene for the epidermal growth factor receptor (EGFR). The FDA also approved a companion diagnostic test, the therascreen EGFR RGQ PCR Kit, to test tumor samples for EGFR mutations and determine whether patients are candidates for treatment with gefitinib.
Under accelerated approvals, however, companies must conduct additional trials to confirm initial indications of patient benefit.

This new approval is based on findings from two studies, including a recent 106-patient single-arm clinical trial that showed a 50 percent response rate in previously untreated patients whose tumors had specific EGFR mutations, as determined by the therascreen test. Only four patients discontinued treatment because of side effects, the most common being rash, diarrhea, and vomiting. The drug’s approval was also supported by findings from a subset analysis of an earlier randomized phase III clinical trial, called iPass, in patients with advanced lung cancer. EGFR mutations are present in up to 15 percent of Caucasian patients and up to 50 percent of Asian patients. Exosomes containing the protein GPC1 could potentially be used to detect early signs of pancreatic cancer in blood, according to a new study. Researchers have identified a potential biological marker for detecting pancreatic cancer in its early stages—a protein attached to vesicles that circulate in blood. For a decade, researchers have been exploring the use of exosomes as potential markers for various diseases, including pancreatic cancer, which is often detected in its advanced stages. To begin, the researchers analyzed blood from 190 patients with pancreatic cancer, 32 patients with breast cancer, 26 patients with benign pancreatic disease, 5 with pancreatic cancer precursor lesions, and 100 healthy donors. The researchers validated their findings in an independent cohort, which included 6 patients with chronic pancreatitis, 56 patients with pancreatic cancer, and 20 healthy donors. High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Mammographic breast density reflects the tissue composition of the breast as seen on a mammogram. The researchers also suggested that the findings could lead to new strategies for preventing and treating bone metastases in women with breast cancer. Because the protein has been associated with the homing of hematopoietic stem cells into the bone marrow at certain regions, or niches, where it is highly expressed, the researchers investigated whether breast cancer cells could co-opt E-selectin to also mediate their movement into the bone.
Through experiments with mice, the researchers showed that breast cancer cells spread preferentially to blood vessels that expressed E-selectin and that interactions between the breast cancer cells and E-selectin allowed the breast cancer cells to enter bone. When they exposed the mice to a drug called plerixafor (Mozobil®), which blocks the CXCR4 receptor and is used to mobilize stem cells into the bloodstream so they can be harvested for stem cell transplants, some dormant breast cancer cells were forced out of the bone marrow. This drug is already being evaluated in human clinical trials for leukemia and multiple myeloma as a way to push tumor cells out of the bone marrow into the blood, where they might be killed more easily by chemotherapy, according to Dr. Price, will also look at what happens to breast cancer cells that are mobilized out of the bone marrow. Even so, different people may respond differently, and, until recently, doctors didn’t know why. Scientists see a future when patients will receive drugs that their tumors are most likely to respond to and will be spared from receiving drugs that are not likely to help. Currently, if you need treatment for cancer, you may receive a combination of treatments, including surgery, chemotherapy, radiation therapy, and immunotherapy. For instance, people with melanoma, some leukemias, and breast, lung, colon, and rectal cancers usually have their cancers tested for certain genetic changes when they are diagnosed. For instance, your cancer may be tested to see if you can join a precision medicine clinical trial. To be sure, check with the trial staff and make sure that you understand your consent form. It takes many years, sometimes decades, of research to develop drugs that target the changes that cause cancer to develop, grow, and spread. In 2011, after several trials failed to show that gefitinib improved outcomes for patients with lung cancer, AstraZeneca, the drug’s manufacturer, withdrew the drug in the United States. Among patients in that trial whose tumors had EGFR mutations, those who were treated with gefitinib had substantially longer progression-free survival than those who were treated with standard chemotherapy. These nano-sized sacs may enter the bloodstream and travel around the body, interacting with other cells. The new study used flow cytometry to show that exosomes released by pancreatic cancer cells have a cell surface protein called glypican-1 (GPC1) that is not found on exosomes shed by other cells.
Compared with healthy donors, all of the patients with pancreatic cancer had elevated blood levels of exosomes containing GPC1, whereas only some of the patients with breast cancer did.
Levels of exosomes containing GPC1 were consistently higher among 5 patients with pancreatic cancer precursor lesions than among healthy donors or 26 patients with benign pancreatic disease, such as chronic pancreatitis.

Based on all of the results, the study authors concluded that exosomes containing GPC1 could be used to develop a noninvasive diagnostic test for early pancreatic cancer. Once inside the bone marrow, the breast cancer cells may remain there for extended periods of time and be protected from attack by chemotherapy and other treatments. Please note that blog posts that are written by individuals from outside the government may be owned by the writer, and graphics may be owned by their creator.
The idea of precision medicine is not new, but recent advances in science and technology have helped speed up the pace of this area of research.
After decades of research, scientists now understand that patients’ tumors have genetic changes that cause cancer to grow and spread. Research studies are going on now to test whether treating patients with drugs that target the cancer-causing genetic changes in their tumors, no matter where the cancer develops in the body, will help them. Which treatments you receive will depend on the type of cancer, its size, and whether it has spread. Since additional genetic changes that can drive cancer may occur over time, you might also have your cancer tested if it comes back or gets worse.
This sample will be sent to a special lab, where a machine called a DNA sequencer looks for genetic changes that may be causing the cancer to grow.
Information from this research is being collected in databases where researchers from across the country can access the data and use them in their own studies. To find out if there are open trials for which you may be eligible, use the search tool at Find a Clinical Trial. In 2003, based on a modest response rate in a clinical trial of patients with advanced lung cancer, gefitinib received accelerated approval from the FDA as a treatment for some patients with locally advanced or metastatic lung cancer. In mouse models of pancreatic cancer, elevated levels of exosomes containing GPC1 were detected earlier than the disease could be found through imaging studies. Breasts with a greater proportion of fibroglandular tissue are said, therefore, to be mammographically denser. In such cases, it is necessary to contact the writer, artist, or publisher to obtain permission for reuse. They have also learned that the changes that occur in one person’s cancer may not occur in others who have the same type of cancer.
With precision medicine, if your cancer has a genetic change that can be targeted with a known drug, you may also receive that drug. The process of looking for genetic changes in cancer may be called DNA sequencing, genomic testing, molecular profiling, or tumor profiling.
For most women, mammographic breast density decreases as they get older, reflecting gradual replacement of fibroglandular tissue by fatty tissue during the normal aging process.Although high mammographic breast density is a well-established risk factor for developing breast cancer, it was unclear prior to this study whether breast density is also associated with the risk of death among women diagnosed with breast cancer.
To be eligible for precision medicine trials, your tumor must have a genetic change that can be targeted by a drug being tested. To address this question the scientists analyzed data from the BCSC, a population-based registry of breast imaging facilities in the United States.
The scientists restricted their analysis to five BCSC registries that consistently collect data on body mass index (BMI). BMI is a poor prognostic factor for breast cancer that is inversely related to breast density and therefore might potentially affect associations between density and breast cancer death.Patients included in the study were 30 years or older at breast cancer diagnosis, which occurred primarily between January 1996 and December 2005.
The patients were followed, on average, for 6.6 years, at which time 1,795 deaths were reported, including 889 from breast cancer and 810 from other causes. To analyze breast density, the scientists used the most widely available measure of breast density currently in clinical use, a score known as the Breast Imaging-Reporting and Data System score, which is given by a radiologist based on visual review of a mammogram. Data on tumor characteristics and other personal and health factors were also analyzed.The analysis of mammographic density showed that breast cancer patients with high-density breasts did not have a higher risk of death from breast cancer than patients with lower density breasts, after adjusting for other health factors and tumor characteristics.
The lack of an association between mammographic breast density and breast cancer death is consistent with findings from an earlier, smaller study that examined this association.This study also found an increase in risk of breast cancer death associated with lower breast density among specific subgroups, particularly breast cancer patients who are obese. Relationship between mammographic density and breast cancer death in the Breast Cancer Surveillance Consortium.

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