Advances in research on metastasis mechanism and novel therapy of breast cancer

Release date: 2015-01-26

Recently, the famous young singer Yao Beina died of breast cancer recurrence, which made her countless fans extremely sad. In recent years, breast cancer has become the second most common disease in female malignant tumors in China, and the mortality rate is the highest, which is a serious threat to women's health. However, the cure rate for early breast cancer is very high. The causes of breast cancer are still unclear, but most are related to estrogen, and some are caused by a series of carcinogenic factors and genetic background, causing gene mutations.

In this article, Xiaobian has carried out a detailed inventory of breast cancer prevention measures, breast cancer cancer cell metastasis mechanism, breast cancer detection methods and breast cancer treatment progress. I hope readers can have a clearer understanding of breast cancer through the introduction of this article. And can better help prevent the occurrence of disease.

First, the prevention of breast cancer

Breast cancer threatens the health of more and more women. According to the Journal of the American Association of Retired Persons, Dr. Debbie Saslow, head of the Gynecologic Cancer Department of the American Cancer Society, said the following methods can help women significantly reduce the risk of breast cancer. .

Good sleep. A new study by Case Western Reserve University found that menopausal women who sleep less than 6 hours a night are twice as likely to develop breast cancer as women with adequate sleep. Dr. Cheryl, the head of the new study, said that 7-8 hours of sleep per night can maintain normal body rhythm and help reduce the risk of cancer.

Reduce weight. A new study involving more than 4,000 women at the Montefior Medical Center in New York, USA, found that obesity increases the risk of breast cancer recurrence by 30% and the risk of death by 50%. The researchers analyzed that adipose tissue increases estrogen levels in women and increases the risk of breast cancer. Fat also increases insulin levels that stimulate tumor growth.

Eat cauliflower. A study by the Harvard School of Public Health found that the incidence and recurrence rate of breast cancer in women who ate cauliflower, cabbage, broccoli and other vegetables were reduced by 62% and 35%, respectively. Vitamin C, carotenoids and polyphenols in this type of vegetable can play a key anti-cancer effect.

drink less. More than 40 studies have found that two drinks a day can increase the risk of breast cancer by 21%, and frequent drinking can also increase the recurrence rate by 19%. American Caesar Medical Group experts said that drinking alcohol will increase estrogen levels in postmenopausal women and increase breast cancer risk.

Diligent activities. A recent study by the University of North Carolina found that walking, growing vegetables, planting flowers, doing housework and other activities for 10 to 19 hours a week can reduce the risk of breast cancer by 30%.

[1] Low-fat diet can help women fight breast cancer

Almost everyone will benefit by reducing the amount of fat in the diet. But a low-fat diet may be especially beneficial for women with breast cancer. A new study, published at the San Antonio Breast Cancer Symposium, suggests that a low-fat diet can prolong the lives of some women with breast cancer.

The preliminary findings were based on women with early-stage breast cancer who participated in the Women's Intervention Nutrition Study, where all women underwent surgery and hormone therapy, or various combinations of chemotherapy and radiation (depending on them) The characteristics of the tumor).

A total of 2,437 study participants, of whom 975 were randomly assigned to a group to restructure their diet. Our goal is to get only 15% of the calories earned by women in this group from fat. To help with this task, they receive eight separate sessions for 16 weeks, and then the dietitian checks every three months. The other 1,462 patients served as controls.

[2] The remaining woman is going to cry: the risk of breast cancer is a cause

In China, breast cancer is the most common cancer in the female group. There are many well-known people such as Li Ting and Asan who are familiar with us. This year, I created the "Biography" of the myth of viewing. The singer who sang the beautiful and mournful theme song "Red Face" is Yao Beina. When she recorded this song in the studio, it was the chemotherapy period after she had finished breast cancer surgery. Yu Juan, a female teacher at Fudan University, who is not much older than her, is not so lucky. She was diagnosed with a late stage of breast cancer. After a year and a half of struggle, she passed away with an infinite love for life, leaving a person who touched countless people. Anti-cancer diary - "This life is not completed."

Professor Shao Zhimin, director of the Breast Cancer Professional Committee of the China Anti-Cancer Association and director of the Breast Cancer Research Institute of Fudan University, pointed out that the characteristics of breast cancer in China are getting closer to the developed countries, but the age of multiple breast cancers is smaller than that of developed countries. And the Dink family is more susceptible to this disease, the central city is significantly higher than the underdeveloped areas. He said that this has a close relationship with the living habits of the urban population.

Only 5% of breast cancers are attributed to heredity, stress, personality, bad habits, etc. are all causes of the disease.

[3] JNCI: Computer simulation analysis of breast cancer risk

Scientists' mathematical models to analyze breast cancer susceptibility genetic data and a range of other risk factors can greatly improve the ability to predict women's risk of breast cancer.

A study has shown that breast cancer prevention strategies can be greatly improved by testing cancer susceptibility genes (such as BRCA1 and BRCA2) and variants of multiple genes that affect breast cancer risk. The study was published in the Journal of the National Cancer Institute. The researchers emphasized that their research strategy is computer simulation analysis, so further research is needed to validate the models they use and to assess prevention methods in real life.

But they say that the use of genetic factors and other factors may make preventive treatment more effective, help doctors to give personalized advice and reduce the number of women with breast cancer.

At the same time, mathematical model analysis means that doctors can tell a 50-year-old woman whether she is among the top 10% of the most at risk for breast cancer, and may help find a preventive treatment strategy to reduce her risk.

[4] The role of obesity in breast cancer

The study of Mandi Murph at Georgia College focuses on the role of obesity in promoting the development of women's cancer (breast cancer and ovarian cancer). Research from the National Institutes of Health grants to identify which biomarkers are produced in blood and body tissues, which may indicate the development of these cancers.

Breast cancer remains the most common malignancy in women in the United States. Studies have shown that although standard treatments can improve the overall appearance and quality of life of these cancer patients, postmenopausal obesity has become a major risk factor for breast cancer.

Because fat cells and cancer cells "feed" each other, they together create a symbiotic environment that allows cancer cells to thrive. Researchers hope to develop biomarker profiles to show which groups of people may be at risk. The lab is working on genetically modified transgenic mouse models to make it obese. It was found that not all obese mice developed breast cancer, but the difference in biomarkers between obese breast cancer mice and non-cancer obese mice may indicate the possibility of breast cancer in obese mice.

[5] Healthy lifestyle may prolong the survival time of breast cancer patients

Exercise, healthy eating and good weight control may help improve the survival of breast cancer patients.

Recently, the researchers included 85 studies and studied more than 164,000 women worldwide. The survival of breast cancer patients may be related to a variety of factors, including healthy weight, reasonable exercise, fiber and soybean diet. Reduce fat intake, especially saturated fat.

However, a report from the American Cancer Institute (AICR) and the World Cancer Research Fund International also pointed out that the available evidence does not provide recommendations for breast cancer patients.

Although it is difficult to give specific recommendations, studies have shown that women with healthy weight and reasonable exercise have higher survival rates before and after breast cancer diagnosis, and the risk of having a second primary breast cancer is lower. .

We need to learn more about other factors (including specific types of breast cancer, breast cancer diagnosis, and cancer treatments and socioeconomic factors) to discover its impact on lifestyle and the association between breast cancer patients' survival.

[6] Prevent breast cancer, pay attention to your skirt size!

Obesity and abdominal obesity can cast a shadow over health, and they are also associated with an increased risk of developing multiple cancers. If you want to control these risks, besides monitoring your weight, it may be a simple and effective way to keep an eye on the size of your clothes. A recent study published in the British Journal of Medical Journals (BMJ Open) showed that changes in the code size of skirts can predict the risk of breast cancer in middle-aged and older women.

The study was conducted by researchers from the University of London and Manchester. The researchers recorded the size of the skirts at the time of youth and menopause and analyzed the relationship between size changes and breast cancer risk. Here, the size of the skirt is used as an indicator of abdominal obesity.

A total of 92,834 female subjects (average age 64 years) were included in the study, and their basic information and the size changes of the skirts were collected through a questionnaire survey. The average size of the subjects at the age of 25 was 12 yards (UK size, about 70 centimeters in waist circumference), while the average size at 64 years old increased to 14 yards (about 75 centimeters in waist circumference), 76% of women. The size of the skirt has risen with age.

[7] Cancer Epidem Biomar: Wearing a bra does not increase the risk of breast cancer

According to a study published in the journal Cancer Epidemiology, Biomarkers & Prevention, a population-based case-control study confirmed no association between bras and increased risk of breast cancer in postmenopausal women.

Breast cancer in developed countries may be more common than in developing countries, and one potential cause is the difference in bra wearing patterns.

The new study found that there is no evidence that wearing a bra will increase the risk of breast cancer in women. After considering how many times a woman wears a bra every day, wearing a bra with a steel ring, or at what age to start wearing a bra, the bra is still not confirmed. Will increase the risk of breast cancer in women.

Some people have suggested in non-professional media that wearing a bra may be a risk factor for breast cancer. Some people speculate that bras may block the excretion of waste around the breast. By now, however, there is only very limited biological evidence supporting the link between wearing bra and breast cancer risk.

[8] JCEM: Individuals with high diversity of intestinal flora are less likely to develop breast cancer

Recently, researchers from the National Cancer Institute of the United States have shown that postmenopausal women may have more beneficial effects on their health if they carry a diverse group of intestinal flora in their bodies. International Journal Journal of Clinical Endocrinology & Metabolism (JCEM).

Since the 1970s, scientists have discovered that intestinal bacteria that make up the gut microbiome affect the function of estrogen in the female body. Estrogen is the most primitive sex hormone in the female body; colonization of intestinal bacteria determines estrogen After being produced, it remains in the body or is excreted with urine and feces. Previous studies have shown that the levels of estrogen and its metabolites circulating in the body are directly related to the risk of breast cancer in women after menopause.

According to researcher James Goedert, women with a diversified gut flora in their bodies have higher levels of estrogen metabolites in their bodies than women with lower intestinal flora. It is suggested that women with higher levels of estrogen have a lower risk of developing breast cancer. The researchers then studied 60 recruited menopausal women and analyzed their urine and stool samples. These women were between 55 and 69 years old, and the researchers performed breasts 6 to 8 weeks before the study. X-ray examination, the results showed normal; after analysis of urine and fecal samples, the researchers said that the diversity of the body's gut flora is directly related to the ratio of estrogen fragments, while the latter is an indicator of breast cancer.

[9] JCO: practicing yoga is good for breast cancer survival and improving quality of life

Dr. Kiekol Glase of the Ohio State University School of Medicine evaluated the effects of yoga on inflammation, mood and fatigue in breast cancer patients. They found that chronic inflammation can lead to a reduction in fuel consumption by the body's function, leading to fragility and disability. If yoga prevents and reduces fatigue and inflammation, then regular practice yoga will greatly benefit your health. The paper was published online in JCO Magazine.

The investigators conducted a three-month randomized controlled trial in which 200 breast cancer patients were randomized to receive two 90-minute yoga sessions per week for a total of 12 weeks or wait for the control group. The main measurement indicators are lipopolysaccharide-stimulated inflammatory stimulating factors interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and MFSI-SF, SF-36 and CES. -D model or scale score.

[10]PLoS Med: Love long ç—£? Beware of breast cancer attack

According to a new study published this week in PLOS Medicine, skin pigmentation, commonly known as sputum, may be a new predictor of breast cancer, researchers Jiali Han and Indiana University, Harvard University and French INSERM colleagues report. Women with more sputum are more likely to develop breast cancer.

The researchers used data from two large prospective cohort studies to conclude the two large prospective cohort studies in the US Nurses' Health Study, which included 74,523 female nurses. For 24 years, and France's E3N Teachers' Study Cohort, including 89,902 women, studied for 18 years.

[11] Good news, sassafras can effectively stabilize breast cancer

When it comes to breast cancer, many women will shudder. It is the biggest killer of women. It will capture the lives of thousands of women every year. The famous "Dream of Red Mansions" actor Chen Xiaoxu is suffering from breast cancer and has lost the United States. Sexy girl Angelina Jolie has been brave in breast cancer to save her life. Cancers with such high prevalence still have no treatment.

Although there is no best treatment for breast cancer, Damien Mikael Hansra and other scholars from the Sylvester Comprehensive Cancer Center of the University of Miami recently discovered a plant that can stabilize breast cancer, Graviola. The Chinese name is Pansy. Hey, the research report of these scholars was published in the June 2014 issue of the English journal "Advances in Breast Cancer Research".

Second, new detection methods for breast cancer

[1] Breast Cancer Res: Developed a new predictive technology for specific regulatory procedures for breast cancer

Recently, Chao Cheng, a researcher at the Norris Cancer Research Center in Dartmouth, said that by observing the expression levels of genes downstream of the regulator in breast cancer, we can identify the genetic characteristics of E2F4, which can help predict estrogen receptors. Positive breast cancer, the results of which are published in the international journal Breast Cancer Research, may provide hope for the development of individualized therapies for the treatment of breast cancer in women.

Research data may help design predictive genomic markers for E2F4 activity in estrogen-positive breast cancer patients, and may also help develop simple clinical testing techniques to help physicians choose individualized therapies to treat different breast cancer patients. . Researchers say that our technology may be highly flexible in the future, and because E2F4 is widely available in many cancers, it can help researchers solve many biomedical problems.

In order to design accurate and rapid genomic testing techniques to determine the level of activity of E2F4-related regulators, the team tracked and predicted the origin of cancer by observing the abnormal behavior of transcription factors, while revealing why abnormal gene expression triggers Loss of control of cell proliferation, promote tumorigenesis, and even metastasis of cancer.

[2] United States: Breast cancer genetic testing is included in the scope of medical insurance coverage

BioTheranostics announced today that its breast cancer genetic testing program has been officially included in the Medicare Reimbursement Coverage Program through the evaluation of commercial insurance companies.

The project assesses the risk of breast cancer in women within 5 years by detecting the level of expression of related genes. The occurrence and proliferation of tumor tissues were determined by detecting two key genes HOXB13 and IL17BR in the estrogen signaling pathway. At the same time, the test can also provide a guiding program for late hormone therapy.

Nicolas Barthelemy, the new president of BioTheranostics, said: "This is an important step in the commercialization of breast cancer testing projects. It is also the only molecular testing program that is included in the company's medical insurance. It can more accurately predict the risk of breast cancer, but also for the later stage. Help to help women avoid unnecessary diseases and improve their quality of life"

[3] PNAS: A new tool for identifying breast cancer tissue

Recent studies have found that more than 40% of patients who have undergone breast cancer surgery need to undergo another operation because the surgeon may not be able to treat the lesions clean enough during the initial surgery. However, researchers at Brigham and Women's Hospital (BWH) have successfully tested a tool they developed that will help doctors better differentiate between malignant breast tissue and normal tissue, thereby reducing the chance of repeat surgery.

This tool, called Desorption Electrospray Ionization (DESI) Mass Spectrometry (or Desorption Electrospray Ionization Spectroscopy), is a molecule that turns a molecule into a charge, called an ion, so that it can be identified by mass spectrometry. The contents of the tissue sample can be identified by ion mass spectrometry. The tool ejects a microfluid of charged solvent onto the surface of the tissue to collect information about the molecular composition and produce a color image that reveals the nature and concentration of the tumor cells.

The researchers used DESI mass spectrometry to observe the distribution and amount of fatty acids, called lipids. These lipids were obtained from 61 samples of breast tissue and normal tissue, which were obtained from 14 breast cancer patients who had undergone mastectomy. This software program is used to characterize breast cancer tumors and to define the boundaries between healthy and cancerous tissues.

[4] New "electronic skin" for early screening of breast cancer

In the detection of breast cancer, manual inspection of breast tissue seems to be a low-tech method compared to other methods such as MRI, but researchers from the University of Nebraska recently developed an "electronic skin". It can detect small tumors in the breast and image these tumors, which may provide some early research foundation for the detection and identification of breast cancer. The related research is published in the international magazine ACS Applied Materials & Interfaces.

In the article, researcher Chieu Van Nguyen said that early diagnosis of breast cancer will help save the lives of female patients, but a small number of breast cancer cells are not always easily detected. Current detection methods, including MRI techniques and ultrasound. Detection technology, although sensitive, is expensive to detect. Although mammography is not perfect, it is often used to screen young women or women with dense breast tissue.

[5] Breast Cancer Res Treat; diagnosis of breast cancer using microsatellite variation

The fight against breast cancer is endless. Recently, researchers at Virginia Tech have discovered a new diagnostic marker that may help clinicians better predict and prevent the disease.

One in eight women may have breast cancer during their lifetime, so it is important to find better predictors. By comparing the breast cancer blood sample genome to a cancer-free individual's sample, the researchers pinpointed some new markers that not only reveal breast cancer risk, but may also benefit breast cancer treatment. The findings were published in the Breast Cancer Research and Treatment.

[6] British research says simple blood test can detect breast cancer

According to a report by the French "Viewpoint" on June 30, the British study found that a simple blood test can detect breast cancer in advance for 10 years.

The report said that a simple blood test may save many lives. According to the French National Institute of Health and Medical Research, despite the decline in breast cancer mortality in the past 14 years, in 2010, there were still 11,500 women who died of breast cancer. However, the results of scientific research published by researchers at University College London in the Journal of Genomics Medicine will greatly reduce this number. According to the researchers, a simple blood test can detect breast cancer in advance for 10 years.

Researchers have found in blood tests that a molecular change increases the risk of breast cancer in women. The marker is associated with the breast cancer gene 1, but the researchers found the marker in women who did not have a mutation due to the disease. According to the British newspaper The Guardian, 10% of women with breast cancer are caused by variants of breast cancer gene 1 inherited from their parents, while the remaining 90% are still unclear.

3. Why does breast cancer metastasize?

[1]Cell death&differ: Chinese scientists discover new strategies to inhibit breast cancer stem cells

Recently, the international biology journal cell death &differentiation published a recent study by scientists from Canada and China. The researchers demonstrated in vivo and in vitro experiments that activation of toll-like receptor 3 (TLR3) promotes the transformation of breast cancer cells into cancer stem cells (CSCs), producing stem cell characteristics, and this CSC-transforming effect of TLR3 requires simultaneous activation of beta catenin and NF. The -κB signaling pathway can occur. This research provides a new strategy for inhibiting CSC production in cancer treatment.

The researchers pointed out that in the 2012 statistics, breast cancer is the second leading cause of death among women. Traditional therapies such as radiotherapy and chemotherapy can eliminate tumor masses, but still do not completely kill a few malignant tumor cells. These malignant tumor cells can still survive and self-renew, and further develop into malignant tumors. Cells are called cancer stem cells. Studies have found that cancer stem cells are resistant to traditional therapies and can be converted from non-tumor stem cells under certain conditions. While TLR3 has higher expression in breast cancer patients with poor prognosis, the relationship between TLR3 and breast cancer cells to tumor stem cells remains unclear.

[2] JCI: Three-negative breast cancer patients should be genetically screened

A study led by the Mayo Clinic found that most patients with triple-negative breast cancer should undergo genetic testing for breast cancer susceptibility genes including BRCA1 and BRCA2 mutations. The results of this study were published in the Journal of Clinical Oncology.

Clinicians need to consider genetic mutations in all three-negative patient susceptibility genes, because there is a lot of valuable information to learn about gene mutation detection, both for the risk of individual recurrence and for the risk of disease in family members.

The study found that nearly 15% of triple-negative breast cancer patients have deleterious mutations in susceptibility genes. Most of these mutations occur in repair genes involved in DNA damage, suggesting that the origin of triple-negative breast cancer may differ from other forms of disease.

Triple-negative breast cancer is a specific subset of breast cancer, accounting for approximately 12% to 15% of all cases. The disease is difficult to treat because triple-negative breast cancer lacks estrogen, progesterone and HER-2 receptors.

[3] Cell: Why does the Hedgehog signaling pathway trigger breast cancer metastasis?

Long-chain non-coding RNAs (lncRNAs) are implicated in breast cancer, but their mechanisms in cancer metastasis and tumor growth remain unclear.

Scientists at the University of Texas MD Anderson Cancer Center report that hedgehog is a unique cellular signaling pathway (known to cause many types of cancer) and may be the underlying mechanism for breast cancer metastasis. This molecule works in synergy with BCAR4 to facilitate tumor growth and metastasis.

Our study of BCAR4 and Hedgehog signaling pathways provides evidence that lncRNAs play an important regulatory role in the progression of invasive breast cancer. Newly obtained evidence suggests that lncRNAs are a new class of regulators in cancer development and progression.

When the hedgehog signaling pathway is aberrantly activated by chemotactic proteins, it allows for increased expression of genes controlled by the GLI2 transcription factor. Transcription factors are proteins that activate other genes. The team found that BCAR4 is required for the activation of the GLI2 control gene.

[4] BJC: Molecular mechanism of abnormal division of breast cancer cells

Recently, researchers at the VTT Technology Research Center in Finland have discovered a previously unknown molecular level mechanism that can partially explain the growth of cancer cells. The study, published in the British Journal of Cancer, found that high concentrations of miRNA-378A-5P molecules can cause abnormal cell division.

The high concentration of miRNA-378A-5P molecules makes the number of chromosomes in cancer cells abnormal, which is a known potential factor for promoting cancer growth and cancer spread. In addition, the researchers found that elevated levels of miRNA378a-5p were associated with the most aggressive forms of breast cancer in breast cancer patients. The goal of the research is to develop new diagnostic methods for breast cancer based on research results.

MicroRNAs are small RNA molecules in cells that regulate gene expression. They play an important role in various normal processes in the human body and regulate cell viability. It is also known that the amount of microRNA abnormally stimulates the occurrence and development of different diseases such as cancer.

[5] PNAS: an enzyme that controls breast cancer metastasis

Recently, researchers at the University of California, San Diego Medical School discovered and identified an enzyme that controls breast cancer metastasis. The findings are published in the latest issue of the Proceedings of the National Academy of Sciences, which provides a new basis for the leading causes of breast cancer death worldwide. According to the American Cancer Society, an estimated 40,000 women in the United States will die of breast cancer in 2014.

"The key message for this study is that we have discovered a way to target breast cancer through an enzyme-mediated approach." First author Wu Xuefeng said he is a postdoctoral fellow at the University of California, San Diego. This enzyme is called UBC13, which is two to three times more abundant in breast cancer cells than normal healthy cells. Although the role of enzymes in regulating normal cell growth and healthy immune system function is well documented, this study was the first to show that enzymes are involved in breast cancer metastasis.

[6] PNAS: biomarkers of aggressive breast cancer

Recently, scientists at Northwestern University have identified biomarkers that are closely related to basal-like breast cancer, a highly aggressive cancer that is resistant to many types of chemotherapy. This biomarker is a protein called STAT3 and may be a potential target for the treatment of this deadly cancer.

Molecular biologists Curt M. Horvath and Robert W. Tell use powerful computational and bioinformatics techniques to detect two cancer subtypes using data from breast cancer patients taken from The Cancer Genome Atlas Gene expression patterns of basal-like breast cancer and luminal breast cancer. They found that in basal-like breast cancer, a small number of genes are activated by STAT3 protein signaling, whereas in luminal breast cancer, this is not the case.

"Can't treat breast cancer as a simple disease," Horvath said. "There are often many molecular processes in cancer that go wrong. We have combed a large amount of data from STAT3 activity in one type of breast cancer (basal breast) In cancer, it is associated with a gene expression pattern characteristic of basal-like breast cancer, but there is no association in another subtype (luminal breast cancer).

[7] Devel Cell: The mechanism by which breast cancer “steals” the energy of breast stem cells for cancer spread and metastasis

During pregnancy, certain hormones may induce special breast stem cells to produce prolactin cells for breastfeeding; recently, in a research paper published in the internationally renowned Journal of Developmental Cell, researchers from the University of California, San Diego Medical School found through research Mammary stem cells associated with pregnant breasts may be directly associated with breast cancer stem cells.

Researcher Professor Jay Desgrosellier said that we have identified a molecular pathway associated with malignant breast cancer, which is also a necessary pathway for individuals to promote lactation during pregnancy. Revealing the underlying mechanisms of mammary gland development during pregnancy is critical to understanding the pathogenesis of malignant breast cancer and the development of novel therapies, and specific drugs that block this molecular pathway may interfere with the progression of breast cancer.

A new type of breast stem cell population is produced during an individual's pregnancy. These stem cells change the structure of the breast and promote the production of the mammary gland to feed the newborn baby. Normally, the breast stem cells are only related to the early mammary remodeling process. At the beginning of breastfeeding, its function will be turned off. The researchers found that stem cell signaling during pregnancy can be blocked by cancer cells, which in turn produces more malignant breast cancer tissue.

[8] Sci Signal: A key protein required for breast cancer metastasis

Nancy Hynes and her team at the Friedrich Michel Institute for Biomedical Research found an important medium for breast cancer metastasis. The protein Memo is not only necessary for cell migration and invasion, but also a good prognostic indicator for patient outcomes.

Due to the tremendous advances in breast cancer treatment over the past two decades, patients are no longer always due to primary breast cancer death, but are metastasized from breast cancer, which spreads to other tissues and causes death. This is a relatively good news, but it poses a challenge to understanding the protein signaling pathways involved in metastasis. A better understanding of the signaling pathways that control cancer cell movement and invasion is clearly needed to develop new anticancer methods.

Nancy Hynes of the Friedrich Mitchell Biomedical Research Institute and her team have identified and further characterized the Memo protein, which plays an important role in the formation of breast cancer metastasis. In this study published in the journal Science Signaling, they found that Memo is required for cell migration and invasion.

[9] Molecular mechanism of tamoxifen resistance in breast cancer

The International Journal of Molecular Cell Biology published the latest research results of the Ggoxiang research group of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, "Snail and Slug mediate tamoxifen resistance in breast cancer cells through activation of EGFR– ERK independent of epithelial–mesenchymal transition”. This article reveals the molecular mechanisms underlying the production of tamoxifen resistance in breast cancer.

Clinically, tamoxifen is the first line of endocrine therapy for estrogen receptor-positive breast cancer patients. The emergence of tamoxifen resistance and tumor recurrence is a major clinical challenge. Ge Gaoxiang's Ph.D. students, Jiang Yan and Zhao Xiaotong, found that the epithelial-mesenchymal transition transcription factor Snail/Slug induces estrogen receptor-positive breast cancer cells by up-regulating EGFR expression and activating its downstream MAPK signaling pathway. Tolerance of tamoxifen. This process does not rely on epithelial-mesenchymal transitions caused by Snail/Slug. This study is important for elucidating the molecular mechanisms of tamoxifen resistance in breast cancer and identifying characteristic biomarkers of tamoxifen resistance and therapeutic target sites.

Fourth, the progress of breast cancer treatment

[1] Roche suffered a huge setback. The new drugs for breast cancer Kadcyla and Perjeta are not as effective as Herceptin?

Just as Roche is still immersed in Kadcyla and Perjeta (Pertuzumab) for the franchise of breast cancer treatment, and has great expectations for it, recently a pot of cold water poured down, suffered a serious setback. Later studies found that the efficacy of these two new drugs could not beat Herceptin and chemotherapy, and that Roche's plan to expand the new drug market was affected by Waterloo, and stocks also declined.

Roche tested the efficacy of Kadcyla and Perjeta relative to Herceptin in 1095 HER-2 positive breast cancer patients who did not receive pretreatment. The test components were Kadcyla plus Perjeta, Kadcyla, Herceptin plus chemotherapy. The results demonstrate that all three treatment regimens can prolong the patient's survival and none of the patients deteriorate. However, whether Kadcyla alone or Kadcyla plus Perjeta combination can not beat the efficacy of Herceptin plus chemotherapy.

Roche spokesperson Ulrike Engels-Lange told the media that Roche had hoped that the two new drugs could prolong the patient's progression-free survival without relying on traditional chemotherapy, although the trial proved that it did not meet this expectation, but was approved. Indications and medications for patients with HER-2 positive advanced breast cancer, the trial failed to subvert the previous results.

[2] The Lancet Oncol: Tamoxifen can reduce the incidence of breast cancer by a third, significantly 20 years

In a research paper published in the international magazine The Lancet Oncology, researchers from Queen Mary University in London have shown that the protective effect of the breast cancer drug tamoxifen can actually last at least 20 years, up to 20 The tamoxifen drug has been reduced by one-third of breast cancer since the study of the year.

In the article, the researchers examined the long-term risks and benefits of tamoxifen in women aged 35 to 70 years with high-risk breast cancer. The researchers said that in the five years, 7154 premenopausal and postmenopausal Women were randomized to take tamoxifen (20 mg daily) or placebo, and the researchers followed the participants on an average of 16 years of follow-up; the results showed that compared to 350 women in the placebo group, 251 Women taking the tamoxifen group had a 29% lower risk of breast cancer and a 35% reduction in the risk of estrogen receptor-positive invasive breast cancer.

【3】新型药物联合疗法可有效减缓恶性乳腺癌恶化

近日，在2014年圣安东尼奥乳癌研讨会上，来自耶鲁大学的研究人员通过进行一项多中心的II期临床研究表示，一种新型的癌症药物组合疗法或可有效减缓激素受体阳性的转移性乳腺癌患者的病情进展。

研究者表示，试验中招募了118名患转移性激素受体阳性的乳腺癌绝经妇女进行研究，这些研究对象再利用芳香酶抑制剂后癌症并没有得到控制;此前研究结果显示，药物硼替佐米和氟维司群的联合用药相比单独使用氟维司群而言可以在12个月里加倍患者的生存率，并且减少患者癌症的总体进展期。

硼替佐米，一种常用于治疗多发性骨髓瘤的药物，其是一种蛋白酶体抑制剂，可以有效抑制癌细胞清理毒性物质;氟维司群可以引发雌激素受体蛋白的积累，当硼替佐米阻断细胞清理雌激素受体蛋白时，这些雌激素受体蛋白就会增大积累的规模进而对癌细胞产生毒性，随后就会放大氟维司群的作用。这两种药物的联合可以使得1年内癌症无恶化患者的比例从14%增加至28%。

【4】艾日布林可延长恶性乳腺癌患者的生命

在利物浦举办的国家癌症研究所癌症(NCRI，National Cancer Research Institute)会议上，来自英国利兹大学的研究者指出，从海绵中开发出的癌症药物艾日布林(Eribulin)可以使得患恶性三阴性乳腺癌的患者平均多存活5个月。

研究者对超过1800名乳腺癌患者进行了两项主要的临床试验，这些乳腺癌患者机体的癌细胞已经开始向机体其它组织转移了，III期临床试验中研究者将艾日布林治疗的患者同标准化疗法的患者的生存情况进行比较;研究结果显示，艾日布林治疗组女性的生存期比标准化疗法治疗的患者多了两个月，三阴性乳腺癌患者的生存期延长尤为明显，艾日布林治疗可以使得三阴性乳腺癌患者生存期增加将近5个月。

癌症的扩散是90%癌症患者死亡的主要原因，当癌症扩散后患者被诊断出患有三阴性乳腺癌，仅有十分之一患者的生存期会达到10年，而如果在发病早期就被诊断出癌症，那么十分之九的患者的生存期会达到10年。Chris Twelves教授表示，我们的研究结果揭示了艾日布林疗法对转移性的三阴性乳腺癌患者生存期的显著性改善，同时对于HER2阴性的乳腺癌患者的生存改善也较为明显。

【5】乳腺癌3号关键基因被发现新药Olaparib或焕发新生

最近，英国剑桥大学公布了一项突破性研究，乳腺癌3号关键基因——PALB2基因被发现，这是自上世纪90年发现BRCA 1和BRCA 2基因突变与乳腺癌有关后，首次发现另一基因与乳腺癌相关。该基因位于人体第16号常染色体上。

研究者还发现阿斯利康目前正在研发的、用于治疗BRCA1/2基因突变引起的乳腺癌DNA修复酶(PARP)抑制剂Olaparib(奥拉帕尼)，在治疗PALB2基因突变引发的乳腺癌同样有效，相关研究发表在近期的Cell杂志上。

该研究或许可挽救新药Olaparib坎坷的命运。Olaparib是一种创新的、潜在的首创口服PARP抑制剂，被用来治疗乳腺癌、卵巢癌以及前列腺癌。Olaparib原本是英国生物技术公司KuDOS Pharmaceuticals的药物，2005年阿斯利康将KuDOS公司收购后，阿斯利康继续开发这种药物。药物Olaparib I期临床实验表现积极，II期实验结果逊色许多，以至于阿斯利康考虑有没有必要进行III期临床实验。2013年，阿斯利康重新启动对Olaparib药物的研究。但最近，FDA认为阿斯利康招募BRCA基因突变患者群体过小以及提供的数据无法充分说明其药效，暂缓批准Olaparib上市。

【6】奇异干细胞有望攻克乳腺癌

中科院上海生科院生化与细胞所曾艺团队在最新研究中首次发现乳腺中的多能干细胞，从而“刷新”了乳腺干细胞性质的现有理论，奠定了乳腺癌干细胞治疗应用的基础。10月19日，相关成果在线发表于《自然》杂志。

成年人的很多器官中存在干细胞，也称组织干细胞。干细胞流失会导致退行性疾病，表现为器官退化、过早衰老等;而过度增殖及病变又会引发肿瘤。乳腺干细胞的病变极有可能是乳腺癌发生的重要原因之一。因此，寻找乳腺干细胞并了解其特性，既是关键的科学问题，又具有重大的临床意义，有助于创新性地开发针对干细胞的药物靶点治疗。

【7】肥胖干扰芳香酶抑制剂治疗乳腺癌的功效

Obesity may affect the efficacy of a common drug, aromatase inhibitors, in the treatment of postmenopausal women with breast cancer. Obesity is now becoming a global trend. It is expected that by 2030, more than half of the world's population will be defined as obesity, obesity and increased risk of multiple cancers and cancers such as colon cancer, endometrial cancer and postmenopausal breast cancer. Poor.

Aromatase inhibitors stop the production of estrogen in postmenopausal women by blocking aromatase. Aromatase converts androgens into small amounts of estrogen, which means that less estrogen can be used to stimulate the growth of hormone receptor-positive breast cancer cells.

Aromatase inhibitors (AIs) prevent the ovaries from producing estrogen, so aromatase inhibitors can only be used in postmenopausal women. Researchers have revealed that the different effects of AI in obese breast cancer patients will help to clarify whether specific AI will produce better results in obese breast cancer patients.

【8】乳腺癌患者的福音：用3D打印完成皮肤和脂肪移植

Laura Bosworth在她绝大多数时间里，谈的最多的是乳房，其中的重点是乳头。在过去的三年时间里，作为TeVido BioDevices的CEO，Bosworth一直在研究如何让自己的产品能够为乳腺癌患者提供帮助。对身患乳腺癌的女性来说，乳房肿瘤切除术和乳房外科切除术所留下来的精神创伤非常大，该公司一直致力于研发人体组织，希望利用3D打印技术进行皮肤和脂肪移植。

TeVido从接受者身上获取脂肪和皮肤细胞，通过3D打印完成皮肤和脂肪移植。该公司的第一款产品是为乳房再造的乳头，不过他们的最终目标是为医疗美容行业提供更多脂肪移植产品。

【9】Mol Carcinogen：达沙替尼有望用于治疗乳腺癌和其他癌症

据Loyola大学芝加哥Stritch医学院研究人员证实：白血病药物—达沙替尼，很有希望用于治疗皮肤癌，乳腺癌和其他一些癌症。

达沙替尼属多酪氨酸激酶抑制剂，用于治疗白血病。但用达沙替尼其他类型肿瘤细胞时，研究人员发现该药物能使肿瘤细胞聚集在一起，从而防止它们迁移。没有迁移能力，癌细胞不能转移。

Mitchell Denning博士和他的同事发现了达沙替尼抑制肿瘤细胞间黏附的背后分子机制。研究人员在Molecular Carcinogenesis杂志报告了他们的研究结果。

达沙替尼(商品名Sprycel)已被批准用于治疗某些类型的白血病。它针对的是一种叫做BCR-ABL的蛋白，后者促进癌细胞的生长。

【10】辉瑞提交突破性乳腺癌药物palbociclib新药申请

辉瑞(Pfizer)8月18日宣布，已向FDA提交其突破性乳腺癌药物palbociclib的新药申请(NDA)，寻求批准palbociclib联合曲唑(letrozole)用于既往未接受过系统治疗以控制晚期病情的绝经后女性雌激素受体阳性(ER+)、人表皮生长因子受体2阴性(HER2-)局部晚期或转移性乳腺癌的治疗。此前，FDA已于2013年4月授予palbociclib突破性疗法，用于ER+/HER2-晚期乳腺癌的一线治疗，该突破性疗法的授予，是基于II期PALOMA-1的中期分析数据。

此前，业界预测，如果获批，palbociclib的年销售峰值将突破30亿美元，在《即将结束临床试验的全球重磅药物TOP 15》榜单中位列第四。辉瑞也信誓旦旦的表示，palbociclib的II期数据就足以获得FDA的认可和批准，尽管该药的III期项目目前仍在进行中。而竞争对手诺华(Novartis)已于去年11月将其CDK4/6抑制剂LEE011推进至III期研究，礼来(Eli Lilly)的CDK4/6抑制剂LY2835219的推进则相对缓慢，研究进程落后于辉瑞和诺华。如果辉瑞这一大胆策略获得成功，palbociclib将率先开启CDK4/6抑制剂市场，LEE011和LY2835219则只能尾随其后，该类药物将为乳腺癌的临床治疗带来重大进步。

【11】Cancer Res：NSAIDs降低乳腺癌肥胖患者癌症复发风险

近日，一项新研究确定，接受激素治疗作为治疗方案一部分的绝经后体重超重或肥胖的乳腺癌患者，使用非甾体抗炎药(NSAIDs)如阿司匹林或布洛芬，乳腺癌复发率显著降低和癌复发时间大大延迟。

这项研究结果发表在8月14日的Cancer Research杂志上，新研究提示了一种减少超重和肥胖绝经后妇女(这些女性复发的相对风险较高)乳腺癌复发率的新可能性。

对人体临床研究和细胞培养实验研究进行回顾性分析，研究人员确定：使用NSAID能减少最常见形式的乳腺癌--ERα阳性乳腺癌的复发率，将乳腺癌患者的无病生成期延长至两年以上。

德克萨斯大学奥斯汀分校癌症研究员Linda deGraffenried等人领导完成了这项研究。研究人员警告说，这些结果是初步的，我们需要进一步研究以确认这些初步调查的结果。

与体重正常的乳腺癌女性相比，超重或肥胖的乳腺癌女性都面临着较差的预后。研究人员首先研究了440名乳腺癌患者的医疗记录，比较那些服用NSAIDs乳腺癌女性患者，和那些没有服用药物患者的预后。

【12】Mol Endocri：科学家发现治疗乳腺癌新型疗法的靶点

近日，来自昆士兰大学的研究人员通过研究发现了一种新型的乳腺癌靶向疗法，研究者George Muscat表示，携带特殊遗传标签的的乳腺癌患者在癌症不扩散的前提下或许更易于存活，相关研究成果刊登于国际杂志Molecular Endocrinology上。

文章中，研究者发现了一种可以被癌症药物靶向作用的蛋白质，Muscat教授表示，我们对来自100位乳腺癌患者的组织样本进行了检测，发现机体酶类PRMT2低水平的个体在癌症不扩散的时候或许存活机会更多一点。而酶类PRMT2具有影响成百上千种基因的能力，因此研究人员必须对这些基因及其产生的蛋白进行检测。

【13】自然武器蜂毒液显示治疗乳腺癌的潜力

近日，Institute for Biomedical Research (IRB Barcelona)科学家利用体外试验发现，用蜂毒液可杀死肿瘤细胞。下一步研究将是测试其在小鼠肿瘤模型中的有效性。

尽管目前正在开发各种化合物对抗癌症，但它们都具有严重的副作用。此外，肿瘤能够对这些化合物产生耐药。

为了抵消上述两个缺点，科学家们设计了一种基于肽的新疗法，利用黄蜂毒液中的多肽，作为预防乳腺癌的潜在新方法。

这种肽具有在细胞质膜形成孔的能力，并穿透进入癌细胞，或诱导癌细胞坏死或触发凋亡，最后导致癌细胞死亡。

【14】Science：靶向癌细胞“种子”或开发出治疗乳腺癌的新型疗法

近日，来自美国南加州大学的研究人员通过研究表明，对于乳腺癌患者来讲个体化医疗或许指日可待，在刊登在国际杂志Science上的一篇研究报告中，研究者揭示了其如何从六个病人的血流中分离出循环的乳腺癌细胞，其中有些致死性的癌细胞就是乳腺癌发生转移的“种子”，这些“种子”可以随着血流在机体中随处流动并且在重要的器官中，比如骨骼、肺部、肝脏甚至大脑中形成二级肿瘤组织。

这项研究中，研究者建立了鉴别新型突变及评估药物敏感性的体系，未来科学家们有可能就会利用从病人机体中分离出的癌细胞来监测患者疾病的进展，以及开发新型的个体化用药策略。

文章中，研究者对6名雌激素受体阳性的乳腺癌病人进行研究，结果发现了雌激素受体基因(ESR1)、PIK3CA基因及纤维母细胞生长因子受体(FGFR2)基因发生了突变，随后研究者对这些突变进行检测，并且结合许多抗癌药物来对突变的肿瘤细胞进行靶向作用，研究者发现药物Ganetspib或STA-9090可以有效杀灭携带ESR1突变的肿瘤细胞。

【15】老药新用—抗疟药或改善乳腺癌对他莫昔芬耐药

雌激素受体阳性乳腺癌的临床前期试验显示，抗疟药物羟基氯喹克服了乳腺癌对他莫昔芬的抵抗。

在有些雌激素受体阳性乳腺癌患者中，同时应用抗疟药物氯喹很可能会推迟甚至逆转抗雌激素药物(例如他莫昔芬)的抵抗。乔治城大学医学中心的RobertClarke医生通过电子邮件对路透健康说到。这种药物联用方式在动物模型中貌似是安全的，并且至少在一个临床试验中做过评估。因为氯喹是一种古老的药物，将其应用于乳腺癌患者的治疗也是非常经济、有效的。

羟基氯喹可以抑制自我吞噬。自我吞噬是乳腺癌细胞诱导的凋亡过程，抗雌激素药物对其有促进作用。目前还不清楚干扰这一过程是否对乳腺癌的治疗有益。

【16】Breast Cancer Res Treat：高胆固醇候选药物Ro48-8071有抗击乳腺癌潜能

近日，密苏里大学研究人员发现一种最初作为降低胆固醇分子的化合物，不仅能停止乳腺癌进展，而且还可以杀死癌细胞。

胆固醇是在所有动物细胞中发现的一个分子，是细胞膜的结构成分，Salman Hyder教授说：因为肿瘤细胞生长迅速，因此他们需要合成更多的胆固醇。科学家在致力于治愈乳腺癌中，往往寻求可能减缓或阻止疾病进展，包括消除癌细胞的替代靶标。在新的研究中，科学家发现靶向癌细胞胆固醇的生成，能导致乳腺癌细胞的死亡。

以往的研究表明，70%的乳腺癌女性是激素依赖性型，因此可用抗激素药物如他莫昔芬治疗。虽然肿瘤细胞可能最初响应治疗，但最终产生耐药性，出现乳腺癌细胞生长和扩散。胆固醇也可有助于抗激素疗法抵抗的发展，因为在肿瘤细胞中胆固醇回转化成激素。因此，这些胆固醇形成途径是对于治疗乳腺癌的潜在靶标。

Source: Bio Valley

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