Best of Breast: news for week ending 21 February 2014

A summary of this news highlights for week ending 21 February 2014 for Breast Cancer and Cancer, from Google Alerts. [Please note:  If you are using Google Chrome for your browser, you may experience issues with viewing the images]

Sorry this is so late – I’ve been away and then caught a cold, so keeping a-breast of the news was a challenge!

All the news developments deserve to share the podium, but I give top-billing to a food substance that has the ability to attack breast cancer cells.  That’s because I’m fed up of research which goes along the lines of “substance BX795 can inhibit the action of signalling pathway xxx” and it turns out that substance BX795 isn’t something that’s found in the aisle at your local supermarket  At least with figs and celery, people who don’t wear white coats and talk in code have a chance!

Image credit: ittybitsofbalance.com

1.  Natural compound in figs and celery attacks HER2 positive breast cancer cells

http://www.sciencecodex.com/natural_compound_attacks_her2_positive_breast_cancer_cells-128144

• A common compound known to fight lymphoma and skin conditions actually has a second method of action that makes it particularly deadly against certain aggressive breast tumors, researchers at Duke Medicine report.
• The compound is called psoralen, a natural component found in foods such as figs and celery, and researchers have long understood that it that works by disrupting DNA replication and causing cell death when activated by an energy source such as UV light.
• Duke researchers have now identified another way the compound works to kill tumor cells, raising the potential for psoralen to be developed as an effective therapy for cancers that are particularly vulnerable to this second mode of action.
• Reporting in the Feb. 14, 2014 issue of the journal PLOS ONE, the researchers detail how psoralen blocks the signaling pathway of the HER2 receptor, which is overproduced in 25 percent of breast cancers, plus ovarian, gastric and other solid tumors.
• When HER2 is overproduced, it fuels uncontrolled cell growth, leading to an aggressive form of cancer. Psoralen shut down this process in experiments using HER2 overexpressing breast cancer cell lines.

For more information:  http://www.dukehealth.org/health_library/news/natural-compound-attacks-her2-positive-breast-cancer-cells

PLOS One:  Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis

2.  Gum disease may increase breast cancer risk

http://www.buckscountycouriertimes.com/life-style/guides/your-health/gum-disease-may-increase-breast-cancer-risk/article_7365c961-c0be-59e1-8a7e-72ee1c61c1df.html

• A recent study by the Karolinska Institute in Sweden on more than 3,000 patients showed those who had gum disease and tooth loss had more than 11 times greater risk of developing breast cancer.
• Although this is the first study to show a link between gum disease and breast cancer, gum disease has also been associated with pancreatic cancer, heart disease, stroke, and premature and low-birth-weight babies.
• Chronic periodontal disease indicated by missing molars seemed to associate statistically with breast cancer

For more information: Periodontal disease may associate with breast cancer.  See also:  Low vitamin D status likely contributes to the link between periodontal disease and breast cancer. [Breast Cancer Res Treat. 2011]

3.  Dense breast tissue drives early stages of cancer

http://www.medicalnewstoday.com/articles/272681.php

• Scientists at the University of Manchester in the UK think that a key biological mechanism may explain for the first time why women with dense breast tissue have an increased risk of developing breast cancer.
• Using structural cells called fibroblasts from high-density breast tissue to generate a “molecular signature,” the scientists found that a cell communication network called JNK1 exhibited more activity in fibroblasts from high-density breast tissue than in lower-density breast tissue.
• Cells are instructed by this network to release chemicals that cause inflammation, which can encourage the formation of tumours.
• “What no one has fully appreciated before are the underpinning mechanisms at play. Using a bioinformatics approach, we have identified the relevant signalling pathways that make dense breast tissue more favourable for tumour formation.
• “This signalling pathway could be used as a biomarker to identify women at higher risk of breast cancer more accurately and earlier than the current methods. Furthermore, there are drugs out there that block these pathways, so that these women could be offered effective chemoprevention.”
• In 2012, Medical News Today reported on a study finding that having dense breast tissue increases risk of cancer returning in women who have previously had breast cancer.

For more information:  http://www.breakthrough.org.uk/news/all-news/study-reveals-more-about-how-denser-breast-tissue-may-drive-cancer and also Cell Cycle journal: JNK1 stress signaling is hyper-activated in high breast density and the tumor stroma: Connecting fibrosis, inflammation, and stemness for cancer prevention

4.  Osteoporosis drug may treat triple-negative breast cancer

http://medicalxpress.com/news/2014-02-osteoporosis-drug-breast-liver-cancers.html

• A drug used to prevent and treat osteoporosis in post-menopausal women may also be able to treat some breast and liver cancers, according to a new study from Oregon State University.
•  Although clinical trials on patients are still needed, in lab tests researchers found that the drug raloxifene, which is marketed under the brand name Evista by Eli Lilly and Co., killed human breast cancer cells that are “triple-negative” as well as liver cancer cells
• Receptors, which are proteins in or on cells, are like a lock. Hormones act like keys to these receptors to unlock different cellular functions. For example, estrogen causes uncontrolled proliferation of breast cancer cells by binding to a receptor. It’s known that raloxifene blocks estrogen from binding to its receptor and thus keeps breast cancer cells from multiplying.
• But what OSU researchers discovered is that raloxifene also binds with a protein called the aryl hydrocarbon receptor (AhR) and kills cancer cells that do not have receptors for estrogen, said Ed O’Donnell, a postdoctoral scholar at OSU who conducted the research.

For more information:  The aryl hydrocarbon receptor mediates raloxifene-induced apoptosis in estrogen receptor-negative hepatoma and breast cancer cells

5.  Breast Cancer Predicted By Small Non-Coding RNA, Previously Considered The White Noise Of Cells

http://www.medicaldaily.com/breast-cancer-predicted-small-non-coding-rna-previously-considered-white-noise-cells

• A team of Canadian researchers have discovered that small non-coding RNAs can be used to predict whether an individual has breast cancer and, furthermore, these molecules may even predict survival outcomes for patients
• Previously, small non-coding RNAs, which are chaotically distributed throughout a cell, were simply thought to be “transcriptional noise.   After all, scientists could never assign them an actual function or see their connection to any disease.
• The researchers tested to see if the expression of the small RNAs in specific locations could be used to predict the presence of disease in another group of tissue samples.
• The test accurately and efficiently predicted the correct disease status for the samples in the new study group.
• “Further work is required but based on our data we believe there is considerable diagnostic potential for these small non-coding RNAs as a predictive tool for cancer,” said Dr. Steven Jones, a professor at Simon Fraser University and the University of British Columbia.

For more information:

Press release:  Small non-coding RNAs could be warning signs of cancer

EMBO press:  The expression level of small non‐coding RNAs derived from the first exon of protein‐coding genes is predictive of cancer status

6.  New hormone receptor targets for breast cancer discovered

http://www.oncologynurseadvisor.com/new-hormone-receptor-targets-for-breast-cancer-discovered/article/334679/

• Androgen and vitamin D receptors can be targeted in breast cancer, according to new research.
• Although estrogen receptors are commonly targeted in breast cancer that is hormone-dependent, this research offers the possibility of expanding the ways that patients with breast cancer are treated with hormone therapy.
• “These findings may change how we treat breast cancer,” said Sandro Santagata, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.
• “Since at least 50% of patients with breast cancer express all three receptors—estrogen, androgen, and vitamin D in their tumor cells, this may allow clinicians to consider triple hormone treatments, which is a new concept, as opposed to treating patients by targeting only estrogen receptors.”

For more information:  Journal of Clinical Investigation (2014; doi:10.1172/JCI70941) Taxonomy of breast cancer based on normal cell phenotype predicts outcome

7.  New test suggests antidepressant Paxil may promote breast cancer

http://www.latimes.com/science/sciencenow/la-sci-sn-antidepressant-paxil-breast-cancer-20140218,0,3273056.story

• A team of researchers from the City of Hope in Duarte, California, has developed a speedy way to identify drugs and chemicals that can disrupt the balance of sex hormones in human beings and influence the development and progress of diseases such as breast cancer.
• In a trial screening of 446 drugs in wide circulation, the new assay singled out the popular antidepressant paroxetine (better known by its commercial name, Paxil) as having a weak estrogenic effect that could promote the development and growth of breast tumors in women.
• The researchers surmised that paroxetine, which was taken by about a quarter of the depressed breast cancer patients in the study, might block the production of a liver enzyme needed to metabolize tamoxifen. The authors of the latest research said paroxetine’s “weak estrogenic” effect “may be responsible, in part, for the observed reduction” in tamoxifen’s effectiveness in that study.

For more information:  City of Hope researchers develop test to assess effect of more than 1,500 chemicals on estrogen

8.  TBK1 expression may represent marker for tamoxifen resistance in breast cancer

http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7Be1f2ee9d-245c-460c-88cb-0e20c1c7ce19%7D/tbk1-expression-may-represent-marker-for-tamoxifen-resistance-in-breast-cancer

• Expression of the innate immune response kinase TBK1 appears to be associated with poor response to tamoxifen treatment in patients with breast cancer, suggesting that this kinase may have a predictive and therapeutic role in breast cancer treatment, study results showed.
• The use of the pharmacological inhibitor BX795 in conjunction with tamoxifen stimulated tamoxifen-induced cell death in breast cancer cells and inhibited tumors. TBK1 expression was higher in patients with breast cancer and found to be positively associated with expression of ER-alpha, ER-alpha S305 and cyclin D1.
• In a significant finding, patients whose tumors expressed high levels of TBK1 had poor outcomes with tamoxifen treatment and demonstrated a higher likelihood of recurrence.
• “Because administration of BX795 together with tamoxifen achieved a synergistic effect on tumor suppression, TBK1 might form a unique therapeutic target for overcoming both intrinsic and acquired tamoxifen resistance in breast cancers,” the researchers wrote.

For more information (needs subscription):  PNAS Plus: Elevated expression of TANK-binding kinase 1 enhances tamoxifen resistance in breast cancer

9.  New finding points to potential options for attacking stem cells in triple-negative breast cancer

http://medicalxpress.com/news/2014-02-potential-options-stem-cells-triple-negative.html

• New research from the University of Michigan Comprehensive Cancer Center and Georgia Regents University finds that a protein that fuels an inflammatory pathway does not turn off in breast cancer, resulting in an increase in cancer stem cells.
• This provides a potential target for treating triple negative breast cancer, the most aggressive form of the disease.
• The researchers identified a protein, SOCS3, that is highly expressed in normal cells but undetectable in triple-negative breast cancer.
• They showed that this protein is degraded in cancers, blocking the cellular off-switch of a feedback loop involving the inflammatory protein interleukin 6, IL6. When the switch does not get turned off, it enables cancer stem cells to grow.
• The researchers tested a drug, bortezomib, in mouse models of triple-negative breast cancer and found that it stops the protein degradation, resulting in the inflammatory loop shutting off, which reduces the cancer stem cells, thereby blocking metastasis. Bortezomib is currently approved for treatment of the blood cancer multiple myeloma.
• This team previously showed that IL6 can stimulate breast cancer stem cells in HER2-positive breast cancers and they are designing a clinical trial which uses an IL6 blocker. The new research suggests that adding bortezomib to the IL6 inhibitor may be a way to target stem cells in triple-negative breast cancer.
• “Now that we unveiled how inflammation is regulated in triple-negative breast cancer, we expect that our studies can be translated into the clinic. The drugs used to block these chemical messengers are already approved for the treatment of rheumatoid arthritis and other inflammation-related diseases, which should facilitate their use in cancer,” says study author Hasan Korkaya, Ph.D., assistant professor at the Georgia Regents University Cancer Center.

For more information:  Nature journal Oncogene – SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model

10.  Pancreatic cancer is on the rise in the UK and could outstrip breast cancer by 2030

http://www.mirror.co.uk/lifestyle/health/miriam-stoppard-pancreatic-cancer-nasty-3145963

• Pancreatic cancer is very aggressive – the fifth most deadly cancer in the UK.
• A few weeks ago a report called for radical improvements in NHS treatment of the condition, which kills about 8,500 people a year.
• The outlook even after an operation isn’t good – only four in 100 patients survive five years.
• On the positive side, the number of specialist pancreatic cancer surgeons has risen in the last few years and there are 25 specialist centres around the country.
• Nonetheless, several dozen patients have paid to have life-saving surgery at Heidelberg University Hospital in Germany because, under guidelines for treating pancreatic cancer in England, some patients are being told their cancer is too far advanced for surgery.
• This is because doctors in some European hospitals are less “risk averse” than doctors in the UK and more ready to perform surgery.

11.  Taxane-first sequencing improved response in breast cancer

• The sequence of taxane chemotherapy before anthracyclines improved the pathologic complete response of patients with breast cancer compared with the reverse sequence, according to phase 3 study results.
• However, the addition of gemcitabine had no effect on response, according to researchers.
• The study included 831 patients who received adjuvant therapy in one of four dosing schedules. The regimens included epirubicin and cyclophosphamide followed by paclitaxel (n=207); paclitaxel followed by epirubicin and cyclophosphamide (n=208); epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine (n=208); and paclitaxel and gemcitabine followed by epirubicin and cyclophosphamide (n=208).

For more information:  Lancet Oncology – Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial

12.  Cancer: ‘Tumour monorail’ can lead cancers to their doom

http://www.bbc.co.uk/news/health-26189827

• A team at the Georgia Institute of Technology designed nanofibres thinner than a human hair which cancers “choose” to travel down.
• Animal studies showed brain tumours could be shrunk by tricking cancer cells into migrating down the fibres.
• The team were working with difficult-to-treat brain cancers – glioblastomas, which have a tendency to spread inside the brain.
• The cancerous cells travel down nerves and blood vessels as they invade the brain.
• The nanofibre technology, reported in Nature Materials, mimics the channels cancerous cells use to move.
• One of the researchers Prof Ravi Bellamkonda said: “The cancer cells normally latch on to these natural structures and ride them like a monorail to other parts of the brain.
• “By providing an attractive alternative fibre, we can efficiently move the tumours along a different path to a destination that we choose.”
• He suggested that controlling the growth of a tumour might be able to make cancer something people live with, like diabetes, if it cannot be cured.  Another idea is to make cancer surgery easier.
• Normally the tumour and the surrounding tissue are removed, but this is a challenge in the brain where removing any unnecessary tissue could have dire consequences.
• Prof Bellamkonda suggested doctors might be able to move a tumour to an area more easily operated on.
• However, the research is still at a very early stage and there will be far more animal studies before it is considered in people.