Best of Breast: news for week ending 1 August 2014

News from the world of Breast Cancer and Cancer, extracted from Google Alerts, for the week ending 1 August 2014.

No real surprises this week, just the weekly melange of suspect carcinogens – foam cups and oral contraceptives [at this rate we might as well stop eating and drinking!] and breakthroughs [on rats] – enjoy!

foamcups

1.  Do foam cups contain cancer-causing chemicals? Leading panel says styrene may be a ‘human carcinogen’

http://www.dailymail.co.uk/health/article-2709577/Do-foam-cups-contain-cancer-causing-chemicals-Leading-panel-says-styrene-human-carcinogen.html

  • Styrene can be ‘reasonably anticipated to be a human carcinogen’
  • Conclusion reached by 10 leading medical experts in the U.S.
  • They stress further research is needed before chemical is regulated
  • American Chemistry Council says styrene has passed most stringent safety tests to be used in food and drink packaging

For more information:  Food Additives and Contaminants journal,  DOI:10.1080/ 19440049.2013.878040, Updated evaluation of the migration of styrene monomer and oligomers from polystyrene food contact materials to foods and food simulants

2.  Immunotherapy targets Her2-positive breast cancer

http://www.dailymail.co.uk/wires/pa/article-2710913/IMMUNOTHERAPY-TARGETS-BREAST-CANCER.html

  • Breast cancer cells that over-produce the HER2 protein are especially aggressive and hard to treat.
  • They account for one in five of the 50,000 cases of breast cancer diagnosed each year in the UK.
  • The new type of immunotherapy has already been shown to be good at targeting cells that produce HER2.
  • But there could be severe side effects due to “collateral damage”, since some normal cells in the heart and lungs also generate small amounts of the protein.
  • Researchers now wants to improve the treatment by modifying it so that the immune system only attacks cells producing HER2 in large amounts.

For more information:  Setting the threshold to target HER2 positive breast cancer using chimeric antigen receptor engineered T-cells

3.  Same cancer, different time zone:  study shows no two single tumor cells in breast cancer patients have an identical genome

http://medicalxpress.com/news/2014-07-cancer-zone.html

  • Just as no two people possess the same genetic makeup, a recent study has shown that no two single tumor cells in breast cancer patients have an identical genome.
  • In fact, depending on the tumor cell, they grow at dramatically different speeds.
  • The study findings may have important implications for the diagnosis and treatment of breast cancer.
  • The research may also assist in efforts to combat the development of chemotherapy resistant in breast cancer patients.
  • The results appeared in this week’s issue of Nature and added to the understanding of “genomic diversity” within tumors.
  • Large-group sequencing studies of breast tumors have identified many prevalent mutations, but have provided limited insight to diversity.
  • The team developed a new sequencing approach called Nuc-Seq, revealing that different subtypes of breast cancer displayed varied tumor diversity.
  • “We found that two distinct ‘molecular clocks’ were operating at different stages of tumor growth. Tumor cells from triple-negative breast cancer had an increased mutation rate, while tumor cells from estrogen receptor positive (ER+) breast cancer did not.”
  • About 75 percent of breast cancers are ER+ and grow in response to the hormone estrogen. They are often treated with hormone therapy.
  • Triple-negative breast cancers account for 15 to 25 percent of all breast cancers and generally do not respond well to hormone therapy or standard chemotherapy.
  • An important question in the field of chemotherapy is whether resistance mutations pre-exist in rare cells in the tumor, or if they emerge spontaneously in response to therapy.
  • “While this question has been studied for decades in bacteria, it remains poorly understood in most human cancers..  Our data suggests that a large number of diverse mutations are likely to be pre-existing in the tumor prior to chemotherapy. Therefore, we expect that measuring genomic diversity will have prognostic value in identifying which patient will develop resistance to chemotherapy.”
  • The study also indicated that genomic diversity may also have useful clinical applications for predicting tumor invasion, metastasis and poor survival in patients.

For more information:  Nature, doi:10.1038/nature13600, Clonal evolution in breast cancer revealed by single nucleus genome sequencing

4.  100,000 genomes project to transform cancer treatment

http://www.theguardian.com/society/2014/aug/01/nhs-genetic-analysis-serious-diseases-diagnosed-treated

  • Tens of thousands of NHS patients are to be invited to donate their DNA for research as part of a project that aims to make the use of genetic data routine in the health service.
  • About 40,000 patients patients with cancer and rare diseases will have their genomes sequenced during the four-year project, which David Cameron claims will transform how serious diseases are diagnosed and treated.
  • Cancer patients will have DNA from healthy and cancerous tissues read so that doctors can work out which mutations are driving the growth of their tumour cells. The information could help medical teams decide which drugs will be most effective in a patient, but will also identify groups for targeted trials of new therapies.
  • Beyond cancer, the 100,000 Genomes Project hopes to improve diagnoses of rare diseases caused by genetic mutations. Though rare individually, they take a huge collective toll on public health. More than 5,000 rare diseases, which affect more than 3 million people in the UK, have been identified.
  • “This is really one of those turning points,” said Jeremy Farrar, director of the Wellcome Trust. “We’ll look back in 20 years’ time and the thought of blockbuster chemotherapy that gave you all those side-effects and adverse events will be a thing of the past.”
  • Patients who donate DNA must sign a consent form to allow academics, doctors and industry access to data. Any relevant information that comes from the sequencing is passed immediately to the patient’s doctor, but medical researchers or pharmaceutical companies must pass an ethical review and have their research approved before they can gain access. No raw genome data can be taken away from the database, and information that identifies a patient will only be made available to doctors treating the person in question.
  • Patients on the DNA database are not guaranteed anonymity, though Genomics England, the company set up by the Department of Health to run the project, said that security measures would make it easier to identify patients through other routes.

5.  Universal cancer blood test moves closer after promising results

http://www.bbc.co.uk/news/health-28443865

  • A British team of researchers has developed what might be a simple blood test that can detect all cancers.
  • The technique involves subjecting white blood cells to ultraviolet light which damages the cells’ DNA.
  • So far tests on the blood of melanoma, colon and lung cancer patients have shown the DNA is more easily damaged compared with healthy volunteers.
  • Those patients with pre-cancerous conditions showed an intermediate level of damage.
  • The researchers believe the results would not be affected by illnesses such as colds or flu that may affect the immune system.
  • “White blood cells are part of the body’s natural defence system.
  • “We know that they are under stress when they are fighting cancer or other diseases, so I wondered whether anything measureable could be seen if we put them under further stress with UVA light.
  • “We found that people with cancer have DNA which is more easily damaged by ultraviolet light than other people, so the test shows the sensitivity to damage of all the DNA – the genome – in a cell.

For more information:  The FASEB Journal, fj.14-254748, Sensitivity and specificity of the empirical lymphocyte genome sensitivity (LGS) assay: implications for improving cancer diagnostics

Oral Contraceptiveds

image credit: nbcnews.com

6.  Recent use of some oral contraceptives increases breast cancer risk

http://www.medicalnewstoday.com/articles/280407.php

  • Numerous studies have suggested that birth control pills increase the risk of breast cancer.
  • Now, a new study suggests that this increased risk may only apply to recent users and is dependent on the formulation of the pill.
  • In the US, two types of birth control pills – also known as oral contraceptives – are currently available.The most common is what is known as the “combined” oral contraceptive. This consists of man-made interpretations of the female hormones estrogen and progesterone. The other oral contraceptive, known as the minipill, only contains progestin – a man-made version of progesterone.The team notes that unlike many previous studies looking at the link between birth control pills and risk of breast cancer, theirs gathered data on patients’ use of the pills from electronic pharmacy records.
  • “The majority of prior studies in the US have relied on self-reported oral contraceptive formulation information, which may be less reliable than pharmacy data,” Beaber told Medical News Today.
  • The results revealed that women who were recent users of oral contraceptives – defined as completing at least one prescription for the pills in the past year – had a 50% increased risk of breast cancer, compared with former users and those who had never used them.
  • But the team found that certain pills had a stronger effect than others.
  • Oral contraceptives containing high-dose estrogen increased breast cancer risk 2.7-fold, while those containing moderate-dose estrogen presented a 1.6-fold increased risk.
  • Oral contraceptives containing low-dose estrogen were found to have no effect on breast cancer risk.
  • Birth control pills containing ethynodiol diacetate – a form of progestin – increased breast cancer risk 2.6-fold.
  • Triphasic combination pills (that consist of three different doses of hormones in every pack) containing 0.75 milligrams of norethindrone – another type of progestin – increased breast cancer risk by 3.1-fold.

For more information:  Cancer Research, doi: 10.1158/0008-5472.CAN-13-3400, Recent Oral Contraceptive Use by Formulation and Breast Cancer Risk among Women 20 to 49 Years of Age

7.  Acupuncture improves quality of life for breast cancer patients using aromatase inhibitors

http://www.sciencecodex.com/acupuncture_improves_quality_of_life_for_breast_cancer_patients_using_aromatase_inhibitors-138564

  • Use of electroacupuncture (EA) – a form of acupuncture where a small electric current is passed between pairs of acupuncture needles – produces significant improvements in fatigue, anxiety and depression in as little as eight weeks for early stage breast cancer patients experiencing joint pain related to the use of aromatase inhibitors (AIs) to treat breast cancer.
  • The results of a randomized, placebo-controlled trial examining the intervention led by researchers at the Perelman School of Medicine at the University of Pennsylvania are published online this week in the journal Cancer.
  • The study is the first demonstration of EA’s efficacy for both joint pain relief, as well as these other common symptoms.

For more information:  Cancer, 30 Jul 2014, DOI: 10.1002/cncr.28917, Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor-related arthralgia: A randomized trial

8.  Scientist to shed light on the role of calcium deposits in breast cancer development

http://www.healthcanal.com/cancers/breast-cancer/53508-rcsi-scientist-to-shed-light-on-the-role-of-calcium-deposits-in-breast-cancer-development.html

  • ‘Microcalcifications’ are calcium deposits that show up on a mammogram as white flecks, and can help identify early breast tumours.
  • It is not clear how or why microcalcifications form, and it was thought that these were nothing more than an ‘artifact’ and had no significant role in breast cancer.
  • However, Dr Maria Morgan (Senior Lecturer in MCT), based at RCSI, believes that these calcium deposits may play an active role in breast cancer – by causing inflammation, they could be encouraging breast cancer cells to grow into a tumour.
  • During the three-year project, Dr Morgan will study microcalcifications produced by different breast cancer cells, as well as non-cancerous cells grown in a lab.
  • Dr Morgan will also identify the different calcium-containing compounds produced by breast cancer cells and investigate if there is a link between the different compounds and the aggressiveness of the breast cancer cells.

9.  Discovery of pro-metastasis breast cancer protein reveals link to neurodegeneration

http://newswire.rockefeller.edu/2014/07/28/discovery-of-pro-metastasis-protein-reveals-mysterious-link-to-neurodegeneration/

  • Researchers have identified a protein that makes breast cancer cells more likely to metastasize.
  • What’s more, the protein appears to trigger cancer’s spread in part by blocking two other proteins normally linked to neurodegeneration, a finding that suggests a tie between two of the most common diseases of old age.
  • In work published earlier this month in Nature, they identify a protein that appears to act as a “master regulator” by blocking tumor suppressor genes and so helping to set metastasis in motion.
  • In the cancer cells, the researchers concluded TARBP2 appears to act as a sort of master regulator by binding to multiple sites on RNA molecules and causing a suite of changes that lead to metastasis, including the destruction of RNAs.
  • By destroying these RNAs, this protein can interfere with the expression of genes, and that appears to be TARBP2’s effect on some metastasis suppressing genes.
  • Indeed, they found TARBP2 is overexpressed in cells prone to metastasizing, as well as in metastatic human breast tumors themselves.
  • When the researchers looked to see what genes might be turned down in these same cells, they found two surprises: APP, responsible for a protein linked to Alzheimer’s disease, and ZNF395, which is associated with Huntington’s disease.
  • In follow-up experiments, the researchers discovered ZNF395 appears to decrease the expression of genes linked to cancer, while a protein segment of APP directly inhibits breast cancer’s ability to metastasize.
  • It turns out TARBP2 tunes down the expression of both of these metastasis suppressor genes; cells prone to metastasis showed higher levels of TARBP2 and lower levels of APP and ZNF395.
  • In cancer cells that tend not to spread throughout the body, the opposite was true.

For more information:  Nature, doi:10.1038/nature13466, Metastasis-suppressor transcript destabilization through TARBP2 binding of mRNA hairpins

10.  Possible brain cancer cure found by scientists

http://www.shinyshiny.tv/2014/07/possible-brain-cancer-cure.html

  • Metastatic brain cancer, caused when cancer from another site spreads to the brain, is one of the deadliest forms of the disease (even more so than when cancer starts in the brain).
  • It affects between 10 and 30% of adult cancer patients, there are no treatment options, and it’s almost always fatal.
  • But a new study from the Cincinnati Cancer Center suggests that there might be a glimmer of hope on the horizon.
  • Scientists from the College of Medicine have found that by combining two natural components, SapC and DOPS (called SapC-DOPS when they’re together), they can kill off cancer cells affecting the brain, while saving healthy tissue.
  • Once combined, SapC, properly known as alysosomal protein saposin, and DOPS, or dioleoylphosphatidylserine can be made into nanovesicles (tiny units that are found in cells or can be artificially created for medical purposes).
  • When scientists injected these nanovesicles into animal subjects, they found that SapC-DOPS started working in the space of 24 hours, prompting a complete recovery in two subjects.
  • “Because metastatic tumors in these models were generated and did not arise naturally from primary tumors, our models do not represent true metastases. However, they still reiterate the essential steps of the metastatic process,” Qi says.
  • “We were still able to show the antitumor effects of SapC-DOPS on human brain tumor cells in models and that SapC-DOPS selectively targets tumor cells in models with brain micrometastases derived from human breast or lung cancer cells.
  • We also showed that SapC-DOPS has cytotoxic effects on metastatic breast cancer cells in cultures.

For more information:  http://www.healthnews.uc.edu/news/?/24900/

11. Neratinib extends disease-free survival in adjuvant treatment of Her2-positive breast cancer

http://www.healio.com/hematology-oncology/breast-cancer/news/online/%7B26793d09-8d96-43f5-a750-ecfd2cc5c947%7D/neratinib-extended-dfs-in-adjuvant-treatment-of-breast-cancer

  • Puma Biotechnology Inc. recently announced that its investigational drug for the extended adjuvant treatment of breast cancer met its primary endpoint in a phase 3 ExteNET trial.
  • The ExteNET trial is a double-blind, placebo-controlled trial of neratinib (PB272, Puma Biotechnology) vs. placebo after adjuvant treatment with trastuzumab (Herceptin, Genentech) among 2,821 women with early-stage HER-2–positive breast cancer.
  • After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ, or death for a period of two years after randomization in the trial.
  • The primary endpoint of the trial was disease free survival. The results of the trial demonstrated that treatment with neratinib resulted in a 33% improvement in disease free survival vs. placebo (HR=0.67, P=.0046).
  • The secondary endpoint of the trial was disease free survival including ductal carcinoma in situ. The results of the trial demonstrated that treatment with neratinib resulted in a 37% improvement in DFS including ductal carcinoma in situ vs. placebo (HR=0.63, P=.0009).

12.  Researchers to Study BRCA1-Related Breast Cancer

http://www.dddmag.com/news/2014/07/researchers-study-brca1-related-breast-cancer

  • BRCA1-related tumors are usually triple negative, meaning they lack estrogen, progesterone, and Her2 receptors, which are effective drug targets for treating other forms of breast cancer.
  • Targeted treatments do not exist for BRCA1-related tumors, which tend to be more aggressive and difficult to manage by conventional therapies. They are also more likely to recur.
  • In its healthy state, BRCA1 acts as a tumor suppressor. The BRCA1 protein, a product of the gene, helps coordinate the repair of damaged DNA in cells before they divide.
  • Tumor-suppressing genes exist in all cells, but if one is mutated, the vital DNA protection is lost
  • If the BRCA1 gene is mutated, it doesn’t properly protect the DNA and can eventually lead to transformation of cells to the cancerous state.
  • Scientists will map out the structure of BRCA1-related interactions in healthy and mutated versions of the protein and determine exactly how each operates at the molecular level.

For more information:  Virginia Tech Carilion Research Institute

13.  Nevaxar Fails to Slow Advanced Her-2 negative Breast Cancer

http://time.com/3034116/nexavar-fails-breast-cancer-study/

  • A Phase 3 trial of cancer drug Nexavar in patients with advanced breast cancer failed to delay progression of the disease, according to the drug’s makers, Bayer and Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
  • The study, called Reslience, evaluated Nexavar in combination with capecitabine, an oral chemotherapeutic agent, in patients with HER2-negative breast cancer.
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