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A “molecular clock” blood test may help identify actively growing tumors in metastatic breast cancer

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Blood tests to monitor the “molecular clock” of breast cancer may help track the growth of multiple tumors around the body and monitor how they respond to treatment. New research suggests.

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Developed by British scientists, this test helps identify the most actively growing tumors when breast cancer spreads throughout the body and helps guide the optimal treatment for individual patients.

This approach was developed following new results from the current legacy study of breast cancer, an innovative rapid autopsy study.

In a new study, the spread of breast cancer to multiple sites follows a traceable order, and the majority of new tumors in distant organs are all formed by cancer cells derived from one cell of the original breast cancer. I found out that.

Although further development is needed, scientists at the Cancer Institute in London and the Royal Marsden NHS Foundation Trust believe that testing is sensitive and relatively inexpensive because it does not require prior knowledge of the patient’s genetic makeup. I will. cancer.

Secondary (or metastatic) breast cancer is the term given to breast cancer that has spread to other parts of the body, such as the bones, liver, lungs, and brain, and is incurable. Despite decades of progress, about 11,500 women still die from breast cancer each year in the UK, and almost all of these deaths are caused by secondary breast cancer.

It is estimated that about 35,000 people in the UK have secondary breast cancer. Secondary breast cancer can be controlled for some time, but is currently incurable and patients continue to be treated for the rest of their lives.

Little is known about how and why breast cancer spreads and what can be done to treat it. This is because secondary breast cancer can form in areas such as the brain, liver, and bones, which can be very difficult and painful to take. Tumor samples for analysis and research.

In a pilot rapid autopsy program led by Royal Marsden consultant breast surgeon Peter Barry, two women with secondary breast cancer in London volunteered to donate cancer tissue for research shortly after their death.

Breast Cancer Now LEGACY research, primarily funded by Breast Cancer Now and sponsored by the Royal Marsden NHS Foundation Trust and Institute of Cancer Research (ICR), allows surgeons, pathologists, oncologists, and researchers to quickly postmortem secondary tumors. I was able to remove and study. Maintains the integrity of important molecules (DNA, RNA, proteins, etc.) within the tumor.

In addition to taking blood samples and biopsies from all secondary tumors, the entire lymph node was also removed and all tissue was rapidly frozen at -80 ° C. Next, researchers led by Professor Andrea Sottoriva of ICR studied DNA from these secondary breast cancer cells in an attempt to better understand how these cancer cells changed over time. ..

LEGACY patient 1 was a 51-year-old woman who died 21 months after being diagnosed with de novo secondary breast cancer. That is, when the cancer was first diagnosed, the cancer had already spread from the breast to other parts of the body.

LEGACY patient 2 was a 35 year old female Diagnosed with breast cancer During her pregnancy. After giving birth, breast cancer was found to have spread to the bones and lungs, and he died 53 months (about 4 years) after the initial diagnosis.

Ten of the twelve tumors found throughout Patient 1’s body were found to have been established by “monoclonal dissemination.” This means that it comes from a single cell of the primary tumor of the breast.

In this patient, breast cancer first spread to the lungs, where new tumors grew and evolved over time. Cancer cells from lung tumors then seeded new tumors in the liver and ovaries in two separate waves. Later, a tumor of the liver spread to the ovary and a secondary tumor developed in the diaphragm. Ovarian tumors also independently re-disseminated secondary tumors of the liver. Overall, only one liver and one ovary sample was not established by monoclonal dissemination.

In Patient 2 with LEGACY, monoclonal dissemination was found to be the only way breast cancer spreads throughout the body. Researchers believe that tracking secondary breast cancer is more achievable if monoclonal dissemination is the primary method of breast cancer spread. I thought about it before.

Later, Professor Sottoriva’s team developed a new type of blood test for cancer DNA to track how secondary breast cancer has spread.

Over time, cells that grow and proliferate actively accumulate molecular marks in their DNA. This will appear in a different pattern. Scientists have found that by analyzing cancer DNA fragments in the blood, it is possible to establish a “molecular clock” for the cancer cells from which the DNA is derived, and to identify how many times it has grown. did.

By analyzing these traceable “molecular clocks” and comparing blood tests to tumors collected during autopsy, the tests build a family tree of cancer cells, and the levels of cancer cell DNA in the blood are Provided information on which secondary tumor. Most active.

However, researchers found a flaw in the way cancer cells added molecular marks to patient 2’s DNA, so to understand how common this challenge is before developing tests for clinical use. Needs further research.

In addition, see data from 11 previous studies primary For breast cancer patients whose disease has spread to the lymph nodes and tissue and blood samples are available, the team confirmed that a “molecular clock” blood test reflects the genetic makeup of the tumor sample.

The authors can use blood tests to track how secondary tumors develop over time and monitor their response to a variety of treatments, including chemotherapy, immunotherapy, targeted therapy, and radiation therapy. I am proposing. With further development, it is hoped that “molecular clock” blood tests can also be used for early detection of recurrence or spread after treatment and may be associated with other forms of cancer.

Our research highlights two central challenges in cancer research and treatment: the deadly capabilities of cancer adaptation and evolution, and the tendency to spread from the first tumor to other parts of the body. ..

LEGACY research has provided a unique opportunity to analyze the genetic makeup of breast cancer after it has spread to multiple parts of the body, shedding new light on the evolutionary process of breast cancer.

By analyzing the characteristics of the “molecular clock” from cancer DNA in the blood, we have identified a whole new way to understand how tumors grow and evolve.

We want to develop blood tests to monitor the progression of cancer in individual patients, and by doing so, provide hope for effective treatment even when the cancer is widespread. “

Professor Andrea Sottriva, Director of Cancer Evolution, New Cancer Drug Discovery Center, London Institute for Cancer

This was a great result of a collaboration with a highly innovative team of ICRs led by Professor Sottoriva. It shows how to potentially sample one active metastatic site in a patient and use the signature of the molecular clock in regular blood tests to test and monitor new therapies in real time.

Obviously, this test needs to be expanded to a larger patient cohort to see if it could be applied not only to breast cancer patients but also to other types of cancer patients. I am deeply grateful to the patients and their families for making this study possible. “

Peter Barry, Surgical Oncology Leader of Current Legacy Studies for Breast Cancer, and Breast Surgeon Consultant at The Royal Marsden Hospital in London

Dr. Simon Vincent, director of research, support and influence at Breast Cancer Now, who funded the research, said:

“Study on how and why breast cancer spreads throughout the body is essential to finding ways to stop breast cancer. This innovative study is made possible thanks to the selfless donations of patients, and breast cancer is a part of the body. It helps to gain insight into how it spreads from one part to another, paving the way for further research to stop secondary breast cancer.

“The development of blood tests that continuously track how a patient’s cancer changes and responds to treatment is more personalized and easily adaptable if a particular treatment becomes ineffective. It’s an exciting step to be able to provide patients with a treatment plan, but more people needed more tests and improvements before this blood test could reach the clinic. ..

“In the UK, 11,500 women and 85 men die of breast cancer each year, so we need to find new ways to stop the spread of breast cancer and effectively treat it when it spreads.

“Anyone worried about the spread of breast cancer can call the free helpline at 0808 800 6000 and talk to one of the professional nurses.”

Breast Cancer Today’s ambition is to help everyone diagnosed with breast cancer live and be healthy by 2050.

Charities fund about a quarter of publicly funded breast cancer research in the UK, No survivors The 2019 campaign emphasizes that 11,500 people still die of breast cancer each year and calls for urgent changes to ensure that all people with secondary breast cancer live in good health for as long as possible.

Breast Cancer We would like to thank Walk the Walk for their generous support as one of the founding funders of the LEGACY study for secondary breast cancer.

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