Best of Breast: news for week ending 24 October 2014

News from Google Alerts for the week ending 24 October 2014, with the focus on breast cancer and cancer.

Loads of goodies this week, from an article on how disruptions to the biological clock can cause breast cancer.  (It’s not the first piece of research into this, but I thought I’d draw your attention to this because when you take your medication and supplements could be affected by the timing).

Also of interest is a cancer clinic in London set up by a leading drug developer who is recruiting patients for a trial of drugs, for whom standard treatment is not working.  From what PR material I’ve read, the group is offering drugs and treatments that are complementary to standard-of-care, including statins and metformin.  It sounds very like the protocol that Life Extension Foundation recommends.  What’s significant is that it’s the first time mainstream doctors (including a highly-reputable oncologist) are sticking their necks out to give patients more options, and it’s nice to see doctors willing to embrace knowledge and techniques that are patient-centred.

There’s also an article on the link between Vitamin D and prostate cancer, and I include this here because prostate cancer is very like hormonally-driven breast cancer.  There has been a lot of research into Vitamin D and cancer, but not many explanations on why it seems to work to help keep cancer at bay.


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1.  Biological clock disruptions increase breast cancer risk

  • The disruption of a person’s circadian rhythm—their 24-hour biological clock—has been linked to an increased risk of breast cancer.
  • The culprit, in this study in particular, is artificial light.
  • “Exposure to artificial light leads to a significantly higher risk for developing breast cancer.  To decrease the use of artificial light, people should avoid working at night and implement earlier bed times.”
  • In the analysis, the research found that employment as a flight attendant was related to an increased risk of breast cancer.
  • “People naturally secrete the hormone melatonin, which helps to regulate the circadian rhythm.  When the sleep-wake cycle is disrupted by artificial light, melatonin secretion is adversely affected.”

For more information:   International Archives of Occupational and Environmental Health, DOI 10.1007/s00420-014-0986-x, Circadian disrupting exposures and breast cancer risk: a meta-analysis

2.  Cancer clinic’s drugs trial for when standard treatment is not viable shows ‘incredible’ signs of success

  • A cancer clinic set up by a leading drug developer whose wife was diagnosed with stage four breast cancer is recruiting up to 5,000 patients with all forms of cancer for a new trial which is showing “incredible” signs of success with his wife.
  • It is hoped the trial will provide breakthroughs for patients for whom standard cancer treatment regimes are not viable or tolerable.
  • Robin Bannister, one of the doctors behind the scheme, helped set up the trial after his wife was given a “bleak prognosis”.
  • Virginia Bannister, from Cambridge, was diagnosed with stage three breast cancer in May 2005, at the age of 41, and had chemotherapy, surgery and radiotherapy.
  • But she had “allergic reactions to the new and best drugs” and the side- effects of the chemotherapies were “horrendous”.
  • After the cancer spread to her lungs in 2012, she again “had an adverse reaction to the cytotoxic drugs so the alternative … was hormone therapy”.
  • Dr Bannister, a veteran of the pharmaceutical industry, said when his wife was diagnosed, it was natural for him to ask: “What do existing drugs do in cancer and is there a treatment regime to offer to people, including my wife, some benefit?”
  • The drugs used in the trial are existing generic drugs and include metformin and statins.
  • Justin Stebbing, a consultant oncologist at Imperial College and Imperial College Healthcare NHS Trust, who is leading the study for the Care Oncology Clinic in Harley Street, which is part of the SEEK group, said it “provides another option for those people for whom standard cancer treatment regimens are not viable, tolerable, available or providing any benefit on a stand-alone basis”.
  • The trial, which is recruiting people aged 18 and over with different kinds of cancer, is being funded by the patients themselves with a £400 initial consultation fee – “which will allow us to keep the data and prolong the study”, Dr Bannister says. There are now 25 patients taking part.

For more information:

3.  UK public petition for Roche to cut price of breast cancer drug, Kadcyla

  • An online petition calls on the drug company Roche to lower the price of its breast cancer drug Kadcyla (trastuzumab emtansine) to make it cheap enough to be made available on the NHS.
  • Almost 29,000 people have signed the petition, launched by breast cancer survivor Margaret Connolly whose niece Helen Mulhearn died from the disease.
  • The drug’s full list price of £90,000 per patient was deemed prohibitive by the National Institute for Health and Care Excellence (NICE).
  • It made a draft decision in August 2014 not to make the drug available on the NHS on the grounds of cost.
  • NICE said the cost would need to be cut by 60% to make it viable.
  • Trastuzumab emtansine targets breast cancer in two ways — by blocking cancer cell growth and destroying cells from within after penetrating their surface.
  • There is evidence of patient benefit in terms of avoidance of side effects and extension of life. Although not available on the NHS, it can be accessed in England through the Cancer Drugs Fund.

For more information and to sign the petition:

4.  Experimental drug shrinks cancer tumours in mice

  • Tumours formed from lung cancer cells completely disappeared in mice treated with an experimental drug
  • “The profound effect on tumour growth in mice shows that switching off TOPK could be a promising approach for treating some cancers in the future” 
  • The drug switches off the TOPK protein, which is thought to promote tumour growth in a number of human cancers, including lung and breast.
  • Researchers from the University of Chicago also found that certain side-effects linked to the drug, called OTS964, could be avoided when the treatment was delivered using a particular method.
  • But when the scientists initially administered the drug it was found to disrupt the processes that control how blood cells are made, causing side-effects that included anaemia and increased risk of infection.
  • To combat this, the drug was placed in tiny bubbles made out of the same material as a cell membrane, and administered using an injection.
  • These bubbles, known as liposomes, were found to work just as well as the initial injections of the drug with none of the blood-related side-effects.

For more information:  (subscription only)  Sci Transl Med 22 October 2014Vol. 6 no. 259 pp. 259ra145DOI:10.1126/scitranslmed.3010277, TOPK INHIBITOR INDUCES COMPLETE TUMOR REGRESSION IN XENOGRAFT MODELS OF HUMAN CANCER THROUGH INHIBITION OF CYTOKINESIS

5.  Finally: A missing link between vitamin D and prostate cancer

  • A study offers compelling evidence that inflammation may be the link between Vitamin D and prostate cancer.
  • Specifically, the study shows that the gene GDF-15, known to be upregulated by Vitamin D, is notably absent in samples of human prostate cancer driven by inflammation.
  • “When you take Vitamin D and put it on prostate cancer cells, it inhibits their growth. But it hasn’t been proven as an anti-cancer agent. We wanted to understand what genes Vitamin D is turning on or off in prostate cancer to offer new targets.”
  • Since demonstrating that Vitamin D upregulates the expression of GDF-15, the scientists, wondered if this gene might be a mechanism through which Vitamin D works in prostate cancer.
  • Initially it seemed as if the answer was no.
  • “We thought there might be high levels of GDF-15 in normal tissue and low levels in prostate cancer, but we found that in a large cohort of human prostate tissue samples, expression of GDF-15 did not track with either normal or cancerous prostate tissue.”
  • But then the team noticed an interesting pattern: GDF-15 was uniformly low in samples of prostate tissue that contained inflammation.
  • “Inflammation is thought to drive many cancers including prostate, gastric and colon. Therefore, GDF-15 may be a good thing in keeping prostate tissue healthy – it suppresses inflammation, which is a bad actor potentially driving prostate cancer.”
  • Additionally encouraging is that the gene GDF-15 was shown to suppress inflammation by inhibiting another target, NFkB.
  • This target, NFkB, has been the focus of many previous studies in which it has been shown to promote inflammation and contribute to tumor formation and growth; however, researchers have previously been unable to drug NFkB to decrease its tumor-promoting behavior.
  • “There’s been a lot of work on inhibiting NFkB.  Now from this starting point of Vitamin D in prostate cancer, we’ve come a long way toward understanding how we might use GDF-15 to target NFkB, which may have implications in cancer types far beyond prostate.

For more information:  (early view) Prostate. 2014 Oct 18. doi: 10.1002/pros.22911, Reduced expression of GDF-15 is associated with atrophic inflammatory lesions of the prostate

6.  Cancer cells can ‘infect’ normal neighbours

  • When a cancer cell throws out its trash, it can turn healthy neighbours into fellow tumour cells, researchers have found.
  • Many cells, including cancerous ones, shed thousands of tiny membrane-bound vesicles called exosomes that contain proteins, DNA and RNA.
  • The process is thought to be a waste-management system, but it may also facilitate cell-to-cell communication: some of these vesicles can then merge with other cells and dump their payload inside.
  •  Previous studies had shown that cancer cells crank out more exosomes than normal cells.
  • The researchers therefore decided to look into how the two types of exosome might differ.
  • They isolated exosomes from cells grown in culture and found that, unlike normal exosomes, those from cancer cells contained the building blocks required to produce the short fragments of RNA called microRNA that can shut off the expression of target genes.
  • Exposure to the cancer exosomes altered gene expression in the normal cells. Those cells then caused tumours when injected into mice.
  • Exosomes from normal cells did not yield tumours, however, and tumour growth was reduced in cells exposed to cancer exosomes in which the microRNA-producing molecular machinery had been disabled.
  • But trying to slow cancer by blocking exosomes is a difficult proposition. It is unclear how that would affect normal cells, he notes, and some exosomes from healthy cells have been shown to contain proteins that prevent cancer.

For more information:  Cancer Cell, DOI: 10.1016/j.ccell.2014.09.005, Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

7.  Stopping anti-CCL2 breast cancer treatment aggravates the disease

  • Scientists show in a study published that a promising therapeutic approach for metastatic breast cancer elicits deleterious effects after cessation of the treatment.
  • Stopping CCL2 inhibition paradoxically increases metastasis formation and leads to premature death thus thwarting the initially beneficial effects of the treatment.
  • This has implications for the design of therapies targeting these processes and indicates that therapeutic approaches to inactivate the chemokine CCL2 should be administered with extreme caution.
  • In experiments using mouse models of metastatic breast cancer the scientists could show that once anti-CCL2 treatment was stopped, large numbers of monocytes, which were sequestered in the bone marrow as a consequence of the treatment, rapidly homed to the tumor and to sites of metastasis, where they induced processes that supported cancer progression.
  • In particular, the scientists could show that a cocktail of factors secreted by the monocytes enhanced cancer cell mobility at the primary tumor, and increased blood vessel formation around proliferating cancer cells at the sites of metastasis.
  • The most deleterious effect was brought about by the factors IL-6 and VEGF-A, whose levels overshot dramatically after anti-CCL2 treatment was stopped.

For more information:  Nature (2014) DOI: 10.1038/nature13862, Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis

8.  Genetic variant protects some Latina women from breast cancer

  • An international research collaboration led by UC San Francisco researchers has identified a genetic variant common in Latina women that protects against breast cancer.
  • Epidemiological data have long demonstrated that Latina women are less susceptible to breast cancer than women of other ethnicities.
  • According to National Cancer Institute data from 2007 to 2009, whites have about a 13 percent lifetime risk of breast cancer, blacks about 11 percent, and Hispanics less than 10 percent. The lifetime risk among Hispanics with indigenous American ancestry is even lower.
  • The variant, a difference in just one of the three billion “letters” in the human genomeknown as a single-nucleotide polymorphism (SNP), originates from indigenous Americans and confers significant protection from breast cancer, particularly the more aggressive estrogen receptor–negative forms of the disease, which generally have a worse prognosis.
  • “If you have one copy of this variant, which is the case for approximately 20% (the range being 10 to 25 percent) of U.S. Latinas, you are about 40 percent less likely to have breast cancer.
  • If you have two copies, which occurs in approximately 1% of the US Latina population, the reduction in risk is on the order of 80 percent.”
  • The newly discovered SNP is on Chromosome 6, near a gene coding for an estrogen receptor known as ESR1.
  • The biological basis of the association between the variant and reduced breast cancer risk is still not known, but their preliminary experiments indicate that the variant interferes with the action of transcription factors, proteins that regulate the expression of the ESR1 estrogen receptor.

For more information:  Nature Communications 5, Article number:5260doi:10.1038/ ncomms 6260, Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25

9.  Breast Cancer Cells Metastasize Post FOXP2 Speech Gene Silencing

  • A scientific team have identified an unexpected link between a transcription factor known to regulate speech and language development, and metastatic colonization of breast cancer.
  • The new findings demonstrate that, when silenced, the FOXP2 transcription factor, otherwise known as the speech gene, endows breast cancer cells with a number of malignant traits and properties that enable them to survive and metastasize.
  • “FOXP2 knockdown in BCCs [breast cancer cells] was sufficient in promoting CSC [cancer stem cell] propagation, tumor initiation, and metastasis,” write the researchers.
  • “Importantly, elevated microRNA-199a and depressed FOXP2 expression levels are prominent features of malignant clinical breast cancer and are associated significantly with poor survival.
  • Our results identify molecular determinants of cancer progression of potential utility in the prognosis and therapy of breast cancer.”
  • These findings agreed with similar results in which the authors determined that miR-199a upregulation and FOXP2 repression are prominent features of aggressive clinical breast cancers and represent independent prognostic parameters for overall patient survival.

For more information:  Cell Stem Cell, DOI: .2014. 10.001, MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis

10.  New analysis of stroma cells may revolutionize breast cancer therapy

  • Stroma cells are derived from connective tissue and may critically influence tumour growth. This knowledge is not new.
  • However, now for the first time, scientists have successfully analysed these molecules out of human tissue.
  • Using modern mass spectrometry, tumour-promoting activities from breast fibroblasts were directly determined from needle biopsy samples.
  • The potential contribution of stroma cells to tumour growth has been widely recognised.
  • It is not easy to understand whether a diseased stroma state supports tumour initiation or, alternatively, tumour- stroma cells are responsible for the formation of such diseased stroma.
  • Main components of breast tissue are epithelial cells and fibroblasts.
  • In case of breast cancer, the epithelial cell may transform while the fibroblasts, remaining genetically unaltered, may change their activation state.
  • The typical activity of cancer associated fibroblasts (CAFs) is similar to wound healing activities.
  • The secreted growth- and survival factors, biologically active at extremely low concentrations, are not only supporting wound healing, but may as well be exploited in case of cancer for further promotion of the disease.
  • The results of the current study may have several consequences.
  • “It is therefore feasible for us to determine to which extent such activities are present and relevant in individual patient samples.
  • “For that aim we are currently developing an assay using blood serum only.
  • Furthermore, it is now possible to use the in vitro model system to test drug candidates interfering with these undesirable cell activities in a targeted fashion. Clinical application of such an additional therapeutic strategy could substantially improve current therapies with respect to life quality parameters and prognosis.

For more information:  J. Proteome Res., Article ASAP, DOI: 10.1021/pr500727h, Proteome Profiling of Breast Cancer Biopsies Reveals a Wound Healing Signature of Cancer-Associated Fibroblasts

11.  Company uses 3D printing to help breast cancer survivors

  • TeVido combines the concept of 3D printing and tissue engineering to literally print custom tissue to rebuild a woman’s breast.
  • “The concept is based on ink jet printers. We would take a sample of her own fat and skin to recreate the nipple which would be our first product, and longer term we could fill lumpectomies,” said Bosworth. “Once the printing process is complete, we would then work with the plastic surgeon to see when would be the right time to do the procedure to put the nipple back on.”
  • Bosworth says this technology could be available in markets within the next five years.

For more information:

12.  New drug approach to treat advanced triple-negative breast cancer

  • Along with AstraZeneca and Bristol-Myers, Merck is developing a drug designed to block a molecule called PD-1–short for programmed cell death protein 1–spurring the immune system into action to attack the tumor cells.
  • Left unchecked, this switch allows cancerous cells to pass undetected.
  • Meanwhile, Roche is testing its PDL-1 drug, designed to inhibit the interaction of programmed death-ligand 1 with PD-1.
  • Merck and Roche are hoping to widen this novel approach to treat advanced triple negative breast cancer, which is notoriously impervious to some of the most effective therapies available for breast cancer, like hormone therapy and drugs that target HER2 receptors.

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