Nature Medicine: Heart disease or breast cancer metastasis! For the first time, scientists have found that heart disease reprograms the immune system, leads to a decline in immunity, promotes breast cancer progression and metastasis.

With the continuous emergence of new therapies, the 5-year survival rate of breast cancer patients is getting higher and higher.according to statistics, there are 3.8 million invasive breast cancer survivors in the United States alone in 2019 [1].if we look at it from a global perspective, the number may be more than 10 million.today, Professor Kathryn J. Moore from the school of medicine of New York University and her research team have published important research papers in the famous medical journal Nature Medicine [2].this research has brought a wake-up call to the majority of breast cancer survivors: take good care of your heart and be alert to heart attack.the Moore team retrospectively analyzed the data from two large-scale prospective studies. Unexpectedly, compared with patients who did not have heart disease after diagnosis of breast cancer, patients with heart disease after diagnosis had an increased risk of breast cancer recurrence by 59% and death due to breast cancer by 60%.they also studied the possible mechanism of heart disease promoting breast cancer progression in mouse models: myocardial infarction (MI) can cause immune cell reprogramming, induce some immune cells to become immunosuppressive phenotype, trigger systemic immune homeostasis imbalance, and accelerate the progress and metastasis of breast cancer."heart attack seems to provide a favorable environment for tumor growth by inactivating the immune system's attack on cancer cells," Moore said.} for a long time, scientists have found that the risk of cardiovascular disease in patients with breast cancer is significantly increased due to the toxicity of treatment and the change of living habits [4,5].moreover, with the improvement and upgrading of treatment methods, the survival time of patients is longer and longer, and the risk of cardiovascular complications is also increasing.however, the impact of heart disease on the development of cancer remains unknown.Moore is an expert in heart disease and director of cardiovascular research center of New York University School of medicine. She noticed a few years ago that the incidence rate of heart disease in breast cancer patients is not low."I wonder if heart attacks affect their cancer," Moore said [6], "and to my surprise, no one has done any research."Professor Kathryn J. Moore, although we often say that cancer is a genetic disease, the occurrence and development of cancer are not entirely determined by genes. Tumor microenvironment and immune capacity of patients are also important factors affecting the occurrence and development of tumors [7]. Br / > it has been found that myocardial infarction can cause peripheral blood mononuclear cell damage to a certain extent.and monocytes are the key regulatory factors of tumor microenvironment, and the increase of monocyte level in peripheral circulation is associated with adverse clinical outcomes of various cancers [9].based on the above information, Professor Moore speculated that heart disease should have a certain impact on the development of breast cancer, and it is necessary to do in-depth research.} This image was published by Raman oza on pixabay. Moore and her colleagues first conducted a retrospective analysis of two prospective case cohort studies of early breast cancer [10, 11] to assess the relationship between new, diagnosed cardiovascular events (such as myocardial infarction or stroke) and cancer outcomes (recurrence and cancer-specific death). the researchers excluded patients who had cardiovascular disease or cardiovascular risk factors at the time of cancer diagnosis, and adjusted multiple covariates for the remaining 1724 patients. at an average follow-up of 11.7 years after diagnosis, the incidence of cardiovascular events after diagnosis of breast cancer was associated with a 59% increase in adjusted cancer recurrence risk and a 60% increase in breast cancer specific mortality compared with patients without cardiovascular events. The data obtained by the Moore team are consistent with previous studies on the association between heart failure and the incidence rate of all cancers. [12-14] } recurrence and death curve of breast cancer patients, as well as relevant data, what is the mechanism behind this? To answer this question, Moore and her colleagues turned to model mice. they injected breast cancer cells into mice, and then divided the mice into two groups. One group was operated to block two coronary arteries of the heart to simulate myocardial infarction, and the other group underwent a sham operation as the control group. 20 days later, the researchers found that the mice in the Mimi group had huge tumors, about twice the size and weight of the mice in the sham operation group. it is obvious that myocardial infarction increases the growth rate of tumor. } changes in tumor volume and weight in mice Moore and her colleagues analyzed the changes in immune cells in the tumor to find out why the tumor grew faster after MI. in general, the level of immunosuppressive cells that inhibit T cell infiltration and anti-tumor response is significantly increased, especially CD11b + ly6g-ly6chi monocytes (or monocytic myeloid derived suppressor cells, m-mdscs). and subsequent studies have shown that the increase of ly6chi monocytes is indeed caused by myocardial infarction. then Moore team used a method to eliminate 90% of ly6chi monocytes in blood and 55% of bone marrow. Miraculously, the tumor volume of mice in myocardial infarction group was reduced by 56%, while that of mice in sham operation group did not change. } after eliminating ly6chi monocytes, the tumor volume of mice was changed. From the changes of immune cells in myocardial infarction group, the proportion of immunosuppressive T cells decreased and the proportion of activated cytotoxic T cells increased after eliminating ly6chi monocytes. } eliminate ly6chi monocytes, changes of immune cells, so how does myocardial infarction regulate the immune system? The researchers also analyzed ly6chi monocytes in bone marrow and blood and m-mdscs in tumors from the perspective of transcriptome. they found that the expression pattern of 235 genes in the MI group was changed compared with the control group, in which the expression of genes related to tumor growth was up-regulated, while the expression of genes promoting immune system activation was down-regulated. and the effect of myocardial infarction on transcriptome is accomplished by epigenetic regulation. } transcriptome data analysis due to similar changes in immune cells in mouse bone marrow, researchers believe that myocardial infarction reprogrammes ly6chi monocytes when monocytes are still in bone marrow, resulting in a large number of monocytes becoming immunosuppressive immune cells. the researchers further confirmed their conjecture through bone marrow transplantation. finally, Moore's team also studied the effect of myocardial infarction on lung metastasis of breast cancer in mice models of primary breast cancer. they found that myocardial infarction did increase lung metastasis of breast cancer. based on the above data, Moore and her colleagues believe that their findings suggest that myocardial infarction, as an acute pathological stress event, can accelerate the progression and metastasis of breast cancer. in terms of mechanism, myocardial infarction leads to the changes of innate immune cells through epigenetic means, forming a systemic immunosuppressive environment and promoting tumor growth and metastasis. the next step is to study how epigenetic changes caused by myocardial infarction occur, so as to find ways to reduce the risk of cancer recurrence and death. however, before the research results appeared, Moore suggested that breast cancer patients can more actively control the risk of cardiovascular disease, such as more exercise. in fact, exercise has been associated with a reduced risk of cancer death. although ASCO in 2020 is over, its impact on cancer treatment in the next few years is just beginning. in order to help you quickly grasp the key points of this year's ASCO and effectively obtain a panoramic understanding of the frontier progress, we have also made full efforts to create the "asco2020 trend interpretation". it comprehensively combs the 9 major cancer species and the key academic research in 300 oral reports, so as to give you a comprehensive overview of the progress of ASCO in 90 minutes.