Best of Breast: news for week ending 3 October 2014

News for the week ending 3 October 2014, for breast cancer, selected from Google Alerts.

The only items that got me excited this week are (1) a new gizmo that combines both MRI and robotics, allowing a biopsy to be taken with more accuracy while in an MRI scanner (I wonder how this is going to be done – I assume the needle must be non-magnetic?) and (2) a breast cancer vaccine trial in Australia – lucky Australians!  Currently the only breast cancer immunotherapy trials in the UK are for Her-2 positive breast cancer.


1.  Image-guided robotics to perform biopsies in MRI scanners

  • Canadarm robotic technology has been adapted to perform breast cancer biopsies inside an MRI scanner, the Canadian Space Agency says.
  • The capability of this system to get the tip of the needle to within a fraction of a millimetre close to the targeted lesion.
  • Most patients approached to participate in the research are in favour of it, because they believe they’ll experience less pain and bruising during the more accurate procedure.
  • The robot itself includes four rotating arms hidden inside a box.
  • The robotic approach inside the MRI is able to perform real-time imaging for radiologists. It also freezes the path taken during the biopsy and reduces trauma for the patient.
  • The early-stage Phase 1 clinical data will be submitted to Health Canada and the U.S. Food and Drug Administration.
  • The goal is to manufacture the technology to sell to hospitals for under $500,000, which is the range of devices purchased by most cancer centres.

2.  New study links low-level alcohol consumption to breast cancer

  • Women who have as little as two drinks a day are at an increased risk of breast cancer, a new University of Victoria study has found.
  • Those women — classified as low-level drinkers — are 8.5 per cent more likely to develop breast cancer than if they had abstained from alcohol.
  • Hazardous drinkers, who have more than three drinks a day, face a 37 per cent risk increase.
  • The meta-analysis confirms what previous studies and authorities around the world have been convinced of:  Alcohol is a major risk factor for breast cancer.  It’s hard to say in any one person that it was just alcohol, but it’s one thing that can tip the probability in the wrong way.”
  • The researchers gathered existing research on the link between breast cancer and alcohol. They found 60 studies published before 2013 — but there were inconsistent findings of the cancer risk for low-level drinkers.
  • Each study depends on comparing drinkers against abstainers, but the definition of abstinence was often faulty.
  • For example, some studies asked subjects if they had a drink in the past week. If the answer was no, they might be classified as abstainers, even if they were formerly heavy drinkers or continued to have less than one drink a week. “The studies that didn’t take account of those things tend to have unhealthier ‘abstainers’ to compare the drinker against.”
  • “When we controlled and adjusted for those biases, we found that — lo and behold — the lighter drinkers, moderate drinkers and low-risk drinkers still had elevated risk, compared with genuine abstainers.”

For more information:  Alcoholism: Clinical and Experimental Research, Volume 38, Issue 8, pages 2297–2306,August 2014, DOI: 10.1111/acer.12479, Methodological Biases in Estimating the Relationship Between Alcohol Consumption and Breast Cancer: The Role of Drinker Misclassification Errors in Meta-Analytic Results

3.  Wonder drug to fight cancer and Alzheimer’s disease within 10 years

  • A wonder drug which could fight cancer, Alzheimer’s disease and diabetes could be developed within 10 years following a breakthrough by scientists.
  • Imperial College has discovered how to turn off an enzyme which is driving many incurable diseases.
  • The NMT enzyme makes irreversible changes to proteins which stop damaged cells from dying and, instead, speeds up their replication, causing cancer.
  • It can be responsible for cancers become resistant to chemotherapy.
  • It is also known to be involved in Alzheimer’s disease, although scientists are unclear as to how it works.
  • But now researchers have identified more than 100 proteins that the enzyme interacts with and have discovered a molecule which acts like an ‘off switch.’
  • The team believes the same enzyme could be driving auto-immune diseases like diabetes and parasitic infections.
  • The chemists used living human cancer cells to identify more than 100 proteins that NMT affects.
  • In one experiment the team programmed cells to die – as would happen in chemotherapy – and discovered that the enzyme stopped the process.
  • Researchers hope that a drug to switch off the enzyme could be used to prevent cancers becoming resistant drugs.
  • The work is so complex that a whole new set of equipment had to be developed over several years to examine the impact of NMT.

For more information:  Nature Communications 5, Article number: 4919 doi:10.1038/ ncomms 5919, Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

5.  New estrogen-related breast cancer mechanism detected that can predict outcome with greater accuracy
  • A previously unknown breast cancer-enabling mechanism has been discovered by researchers from the University of Illinois at Urbana-Champaign.
  • The unfolded-protein response (UPR) pathway protects cells from stress and initiates the production of chaperone proteins.
  • These proteins fold and package other proteins, preparing cells to divide and grow. Because these chaperones are essential to the division of cells, they are now a popular target for cancer treatments.
  • Scientists know that the UPR is activated as part of a stress response in scenarios when a cell is lacking oxygen or nutrients or is attacked by drugs.
  • The activation of the UPR prepares the cell for growth, division and survival under stress.
  • The major new finding is that the UPR is initiated by estrogen even before the emergence of any stresses associated with UPR activation.
  • “This is a new role for estrogen in the pathology of cancer. Others have shown that stress activates this pathway, helping to protect some tumors. What is new is our finding that estrogen can pre-activate this pathway to protect tumors.”
  • The signal that activates the UPR pathway occurs when estrogen binds to its receptor, which causes a stockpile of calcium to flood into the cell.
  • It’s also a signal that many researchers think has something to do with cell proliferation. The calcium itself may be a proliferation signal.
  • As well as protecting cells, though, the UPR can also trigger apoptosis – a kind of “cellular suicide” – in cases where a normal cell is exposed to too much stress.
  • However, when the UPR is activated by estrogen, this cell-suicide response is “blunted,” allowing cancer cells to survive and resist drugs.
  • In another arm of the study, the researchers carried out a computer analysis of breast cancer data – investigating UPR-related gene expression – from women who had been diagnosed up to 15 years prior.
  • The results demonstrate that among women with estrogen-receptor-positive breast cancer who received tamoxifen as a treatment, those with “overexpressed” UPR were 3.7 times more likely to have breast cancer recurrence.
  • Looking at outcomes 10 years after diagnosis, 15% of women with the highest level of UPR-gene expression were cancer-free, compared with 80% of women with the lowest level of UPR expression.
  • UPR activation is a very powerful prognostic marker of the course of a woman’s disease.
  • Our marker helps identify breast cancers that are likely to be highly aggressive and therefore require intensive therapy.

For more information:  Oncogene 0, (29 September 2014) | doi:10.1038/onc.2014.292,  Anticipatory estrogen activation of the unfolded protein response is linked to cell proliferation and poor survival in estrogen receptor α-positive breast cancer

6.  DNA discovery links insulin-like growth factor pathway and regulation of ER positive breast cancer

  • It has long been thought that the insulin-like growth factor pathway (IGF) is important in cancer development, but its exact role has been unclear.
  • Researchers have discovered that women with a specific DNA variant that reduces their levels of a specific protein (IGFBP5) in this pathway are at increased risk of developing breast cancer.”
  • The identified variant, rs4442975, is associated with ​estrogen receptor positive (​ER+) breast cancer, where estrogen receptors are over-expressed. This category comprises around 70 percent of breast cancer cases.
  • The researchers hope that a new targeted drug, one that would prevent breast tumor development, could be developed from the most recent findings.
  • Resarch suggests that the results could be used in future genetic tests to identify women likely to be at the highest risk of developing the disease.

For more information:  Nature Communications4, Article number: 4999doi: 10.1038/ ncomms 5999, Evidence that breast cancer risk at the 2q35 locus is mediated through ​IGFBP5 regulation

7.  How A Simple Blood Test For Calcium Could Detect Cancer Earlier

  • Research has shown calcium in the blood could provide an early warning of certain cancers, especially in men.
  • Even slightly raised blood levels of calcium in men was associated with an increased risk of cancer diagnosis within one year.
  • The discovery, reported in the British Journal of Cancer, raises the prospect of a simple blood test to aid the early detection of cancer in high risk patients.
  • Hypercalcaemia – a higher than normal calcium reading – was associated with a wide range of cancers, chiefly lung, prostate, breast, bowel, and those affecting the blood such as leukaemia and myeloma.
  • While the condition was already known to occur in up to a fifth of cancer patients, this is the first time it has been shown to pre-date diagnosis.
  • A normal level of calcium in the blood is between 2.1 and 2.5 millimoles per litre (mmol/L).
  • In men, even a slight increase outside this range (2.6 – 2.8 mmol/L) was found to increase the risk of cancer being diagnosed within one year by 11.5%. Above 2.8 mmol/L, the risk rose to 28%.
  • The effect was much smaller in women, with similar calcium elevations increasing cancer risk by 4.1% and 8.7% respectively.
  • One reason for the difference could be that women are more likely to experience hypercalcaemia due to over-active parathyroid glands, which has nothing to do with cancer. In the study, this would make the link with cancer less noticeable in women.
  • Men rarely get this condition, so their hypercalcaemia is more likely to be due to cancer.

For more information:  British Journal of Cancer 111, 1410-1412 (23 September 2014) |doi:10.1038/bjc.2014.433, The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

8.  Tumor Infiltrating Lymphocytes Predict Response to Neoadjuvant Chemotherapy in Breast Cancer–to-Neoadjuvant-Chemotherapy-in-Breast-Cancer

  • A high level of tumor infiltrating lymphocytes (TILs) may be a marker of pathologic complete response (pCR) to neoadjuvant chemotherapy in breast cancer, especially in patients with triple-negative or HER2-positive disease.

For more information:  J Clin Oncol. 2014;32(suppl 26; abstr 138), Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis

9.  Diagnostics company uses epigenetics principles to develop metastatic breast cancer test

  • Women with breast cancer virtually never die from their primary tumor. Rather, the vast majority – nearly 90 percent – of solid tumor deaths happen because it’s metastasized through the blood.
  • Only a fraction of tumors are biologically capable of metastasizing.  Metastatic disease isn’t something that randomly happens – it’s driven by the biology of the individual tumor.”
  • In lung cancer, perhaps 90 percent of tumors are metastatic, explaining the high mortality rate of the disease. When looking at breast cancer, only 35 percent of women would develop metastatic disease.
  • MetaStat’s built around the premise that a common pathway explains how all epithelial-based cancers metastasize.
  • Here’s where the epigenetics come in: Since 80 percent of solid tumors are epithelial, they likely come from the same origin cell type.
  • When a fetus is developing, an embryonic protein called the Mena Protein participates in the maturation of the central and peripheral nervous system.
  • Post partum, however, expression of this protein stops.
  • However, all epithelial-based tumors, including metastatic breast cancer, are said to express a lot of the invasive isoform of this Mena protein.
  • The principal driver of whether these tumors can metastasize or not is determined by how much of this Mena invasive isoform these tumors produce.
  • The company was formed with the initial plan to develop therapeutics around Mena protein expression levels in metastatic solid tumors.

For more information:  Oxford Journals Medicine & Health, JNCI J Natl Cancer Inst, Volume 106, Issue 8, 10.1093/jnci/dju136, Tumor Microenvironment of Metastasis and Risk of Distant Metastasis of Breast Cancer

10.  Perjeta shows “unprecedented” survival benefit in Her-2 positive breast cancer

  • Patients with a type of breast cancer known as HER-2 positive, which makes up about a quarter of all breast cancers, who were given Perjeta on top of older medicine Herceptin and chemotherapy lived 15.7 months longer than those on Herceptin and chemotherapy alone.
  • “The survival improvement of nearly 16 months … is unprecedented among studies of metastatic breast cancer,” lead researcher Sandra Swain from the Washington Hospital Center told the European Society for Medical Oncology annual congress on Sunday.
  • Researchers had previously reported the Perjeta drug regimen significantly extended progression-free survival, or the period of time patients live without their disease worsening, but the final overall survival data has taken longer to collect.
  • The median overall survival time was 56.5 months for those given Perjeta against 40.8 months for patients taking only the older drugs.
  • Both Herceptin and Perjeta are antibodies designed to block the function of HER2, a protein produced by a cancer-linked gene. Pertuzumab binds to a different part of the same protein, which makes combining the two drugs extra effective.

For more information:  ESMO 2014 Press Release: Pertuzumab Adds 16 Months Survival Benefit to Trastuzumab and Chemotherapy Treatment for HER2-Positive Metastatic Breast Cancer

11.  Palbociclib and Bemaciclib slow down advanced breast cancer

  • Pfizer’s palbociclib doubled to 20.2 months the time in which patients’ advanced breast cancer did not progress.
  • In an unrelated study, Lilly’s drug, bemaciclib, aided 61 percent of patients with metastatic, hormone-sensitive breast cancer, meaning the size of their tumors shrunk by 30 percent or did not increase for 24 weeks.
  • The CDK 4/6 inhibitors target cyclin-dependent kinases, part of a tumor cell’s pathway to divide and grow.
  • The drugs shut them down, which can cause the tumor to shrink as the cells die. The therapies may also be used long term by patients to make sure their cancers do not come back.
  • The treatments are also being studied in other tumor types, such as lung cancer.
  • The study also looked at the drug’s survival benefit, which showed a trend toward longer survival without being statistically significant.
  • Patients taking palbociclib lived about four months longer, in the analysis, than patients on Femara alone. Not enough patients in the trial have died, though, for there to be a definitive result.

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