Best of Breast: news for week ending 7 March 2014

Updated March 2016 – For more information on GcMAF, please join the GcMAF and GcMAF Cancer forums on Facebook – they are closed groups, so you have to wait for your membership to be confirmed.  They contain up-to-date information on sources of GcMAF, and also feedback and contributions  by people who are using GcMAF.

A weekly round-up of the news on the breast cancer and cancer front, culled from Google Alerts, for the week ending 7 March 2014.

The week started off slowly, with the usual bog-standard research on gene expression and chemotherapy.  (I had a minor panic, thinking I was going to have to invent something sensational (preferably with rats or mice)!)

Then at the end of the week, not one, not two, but THREE juicy news items suddenly appeared, all vying for pole-position.

In the end I went with the 10-minute breath test for detecting breast cancer as Number 1, because it is the answer to the squashing nightmare that is the mammogram [did you know that a mammogram applies a pressure of 20kg on the breasts?  If men had to have mammograms for their testicles, an alternative would have been found years ago!]  The incredible news is:  it’s not at the rat/mouse trial stage, it’s commercial [swoons].  I wonder how many women will have the guts to take the test though.  I have friends who would rather avoid any tests than find out they may potentially have cancer.

Item 2 is one of my favourite topics of interest, Vitamin D (and here’s my post – Vitamin D, are you getting too much?).  There is some debate on what is considered the optimal level of Vitamin D (too high and people died from diseases other than cancer), and I used to ere on the side of caution, but the GcMAF clinic ( uses up to 20,000 IU per day and once the upper limit of the reference range is reached, up to 5,000 IU.  I met a woman who had ovarian cancer and she told me that in the summer months, the shrinkage of her tumour was more than that in the winter months.  She ascribed this to the fact that there was more sunshine in the summer, and her body was able to produce the Vitamin D she needed.  Moral of the story: please supplement with Vitamin D if you have cancer.

The third item isn’t strictly about breast cancer, but it’s an amazing article about how brentuximab, a monoclonal antibody, got rid of all the tumours (70 of them) in a man with metastatic cancer – anaplastic large cell lymphoma.  The before-and-after photos are nothing short of a miracle … best of all, it’s within our reach, and offers hope to everyone with cancer.

Oh yeah … find out why you should become an astronaut if you have cancer … and another item shows that chemotherapy damages the methylation DNA of normal white blood cells, thus causing inflammation and fatigue.   To those who’ve had chemotherapy and suffered the side-effects, this study seems to be from the University of Obvious.  Now if only those brainy people who came up with the study can find a way of protecting normal cells from the side-effects of chemotherapy … .

BreathLink kit

1.  Ten-minute breath test that can detect breast cancer

  • The BreathLink kit is being developed by a US firm and is already on sale in Europe. It begins with a woman breathing for two minutes into a breathalyser.
  • The air is fed into a machine which analyses the levels of chemicals. The results are crunched by a computer, which determines whether the chemical pattern is a sign of breast cancer.
  • Research published in the journal PLoS ONE shows it to be at least as accurate as mammograms.
  • Michael Phillips, a professor of medicine at New York Medical College, and the brains behind the breath test, said: ‘We know that if you get a negative result on the breast test, there is a better than 99.9 per cent chance that a woman doesn’t have breast cancer.
  • The test, which is being developed by Dr Phillips’ firm Menssana Research, is already on sale in Europe.
  •  By taking the embarrassment out of the procedure, it could also lead to more woman coming forward for testing, saving lives.
  • It would also mean that women aren’t exposed to radiation during testing.

For more information:  PLOS One, DOI: 10.1371/journal.pone.0090226, Rapid Point-Of-Care Breath Test for Biomarkers of Breast Cancer and Abnormal Mammograms

2.  Vitamin D Increases Breast Cancer Patient Survival

  • Breast cancer patients with high levels of vitamin D in their blood are twice as likely to survive the disease as women with low levels of this nutrient, report University of California, San Diego School of Medicine researchers in the March issue of Anticancer Research.
  • In previous studies, Cedric F. Garland, DrPH, professor in the Department of Family and Preventive Medicine, showed that low vitamin D levels were linked to a high risk of premenopausal breast cancer. That finding, he said, prompted him to question the relationship between 25-hydroxyvitamin D — a metabolite produced by the body from the ingestion of vitamin D — and breast cancer survival rates.
  • “Vitamin D metabolites increase communication between cells by switching on a protein that blocks aggressive cell division,” said Garland. “As long as vitamin D receptors are present tumor growth is prevented and kept from expanding its blood supply. Vitamin D receptors are not lost until a tumor is very advanced. This is the reason for better survival in patients whose vitamin D blood levels are high.”
  • Women in the high serum group had an average level of 30 nanograms per milliliter (ng/ml) of 25-hydroxyvitamin D in their blood. The low group averaged 17 ng/ml. The average level in patients with breast cancer in the United States is 17 ng/ml.
  • “The study has implications for including vitamin D as an adjuvant to conventional breast cancer therapy,” said co-author Heather Hofflich, DO, UC San Diego associate professor in the Department of Medicine.

For more research:  Anticancer Research, March 2014 34 (3) 1163-1166, Meta-analysis of Vitamin D Sufficiency for Improving Survival of Patients with Breast Cancer

3.  Targeted treatment with Brentuximab  offers hope to cancer patients


Now you see it …


Now you don’t.

  • These stunning “before” and “after” scans of cancer patient Ian Brooks released by the Christie Hospital in Manchester last week, looked almost too good to be true.
  • Mr Brooks, an electrician from Bolton, has a rare, aggressive cancer called anaplastic large cell lymphoma (ALCL), which other treatments had failed to control. With about 70 tumours throughout his body, he was thought to have only weeks to live.
  • He became the first patient outside the US to take part in a small, early phase trial of a new drug called brentuximab – and the scans revealed that, after just 12 weeks of treatment, all the tumours had disappeared.
  • At 47, he is now in full remission – as were well over half the patients who took part in the study. Its results, published last year, were so good that the drug has since been licensed for ALCL and is currently available through the NHS Cancer Drugs Fund.
  • Brentuximab is a type of monoclonal antibody, or MAB. These drugs, used successfully in cancer treatment for years, stick to abnormal proteins on the surface of cancer cells. They work in different ways, depending on the specific protein they target. They may for example, block cancer cells from proliferating, cut off their blood supply or help direct cancer-fighting immune cells to the tumour site.
  • One of the best known is trastuzumab (Herceptin), which is now used successfully in breast cancer treatment.
  •  The antibody is combined with an anti-cancer drug called vedotin, so powerful it could not be used in standard chemotherapy. The antibody targets the protein on the cancer cell, called CD30 – and it then delivers vedotin straight to the tumour.


4.  Cancer research on orbiting space labs could reveal cure clues

  • Cancer research in the weightlessness of space could help develop drugs targeting tumors that don’t respond to current treatments, a U.S. journal reports.
  • Research performed on the Chinese orbiting lab Shenzhou-8, launched in 2011, has shown some tumors seem to be much less aggressive in the microgravity environment of space compared to their behavior on Earth, researchers have reported in the Federation of the American Societies for Experimental Biology Journal.
  • “Microgravity can be approximated on Earth, but we know from the literature that simulated microgravity isn’t the same as the real thing,” said Daniela Gabriele Grimm, a researcher at Aarhus University Denmark and one of the authors of the FASEB paper.
  • Cells grown in space arrange themselves into three-dimensional groupings that more closely resemble what happens in the body, she said.
  • “Without gravitational pull, cells form three-dimensional aggregates, or spheroids,” Grimm explained. “Spheroids from cancer cells share many similarities with metastases, the cancer cells which spread throughout the body.”
  • Extract from paper:  “It is well known that cells cultured under microgravity show an increase in apoptosis. For instance, human lymphocytes cultured in real microgravity on the International Space Station exhibited an increase in programmed cell death. Endothelial cells displayed 30% apoptotic cells when grown on the RPM, even if they remained adherent. Similar data were reported for other cell types. Thus, the question arose whether apoptosis and spheroid formation are independent cellular reactions under altered gravity conditions or whether initiation of an early phase of apoptosis could be a step involved in the transition from 2D to 3D cell growth. “

For more information:  Federation of the American Societies for Experimental Biology Journal,  doi:10.1096/fj.12-215749, “Gravity-sensitive signaling drives 3-dimensional formation of multicellular thyroid cancer spheroids”

5.  Tracking Single Tumor Cells With New Imaging Method in Fight Against Cancer


Zurich group’s imaging mass cytometry analysis of tumor heterogenity

  • Setting out to determine a tumour’s cell profile, its neighbourhood relationships and the circuit structure within and in between cells is a highly complex endeavour.
  • This is because the biomarkers, i.e. the specific molecules of the various cell types and their circuits, have to be measured in their spatial relationships.
  • “With our method it is possible to obtain a comprehensive picture using a novel imaging technique that currently can simultaneously record 32, and in the near future more than one hundred biomarkers”, explains Prof. Bernd Bodenmiller from the Institute of Molecular Life Sciences at the University of Zurich in cooperation with the Trace Element and Micro Analysis Group  of ETH Zurich and University Hospital Zurich.
  • Furthermore, the information about the cells’ neighbourhood relationships is kept and their direct impact on the cellular switch and control circuits can be visualised.
  • The initial measurement results of the new biomarker technique for breast cancer have revealed the heterogeneity of tumours. As a consequence of major growth, some tumours suffer from oxygen deficiency on the inside, other misuse the body’s own immune cells to drive their growth. Cell-cell interaction and cell location in the centre or on the edges of the tumour also have a decisive influence.
  • Source: written by Media Relations of the University of Zurich and first published

For further information:

Giesen C, Wang HAO, Schapiro D, Zivanovic N, Jacobs A, Hattendorf B, Schüffler PJ, Grolimund D, Buhmann JM, Brandt S, Varga Z, Wild PJ, Günther D & Bodenmiller B. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nature Methods, published online 2nd March 2014. DOI:10.1038/nmeth.2869 

6.  Imprint of chemotherapy linked to inflammation in breast cancer survivors

  • Many breast cancer survivors experience fatigue and other debilitating symptoms that persist months to years after their course of treatment has ended.
  •  Now researchers at the Winship Cancer Institute of Emory University have found clues that may explain how these symptoms can linger.
  • Chemotherapy, one of the major treatments for breast cancer, can leave a long-lasting epigenetic imprint in the DNA of breast cancer patients’ blood cells. That imprint is associated with biological signs of inflammation up to six months after the completion of treatment. Inflammation in turn is believed to cause symptoms like fatigue.
  • That achy, tired feeling that comes from the flu is caused by inflammation, the body’s natural response to infection or a wound – but it usually disappears once an illness is over.
  • In patients being treated for cancer, fatigue has also been linked to inflammation and up to 30 percent of breast cancer survivors experience persistent fatigue long after treatment has ended.
  •  In the current study, all the women went through partial mastectomy surgery. Some received varying forms of chemotherapy, and all received radiation at the end. They found that women who had been treated with chemotherapy exhibited changes in the methylation of the DNA in their white blood cells. Some of these changes were still present six months after radiation.
  • Methylation is an epigenetic alteration in DNA, which does not change the A/C/G/T “letter” information in the DNA but does change how that information is read by the cell, influencing whether a gene is turned on or off.
  • The researchers scanned hundreds of thousands of potential sites of methylation; only eight sites were reliably altered in women who received chemotherapy, and changes at half of those sites were visible six months later.
  • The biology connecting this handful of sites to inflammation remains unclear; the eight sites were not in genes that encode inflammatory signaling proteins secreted into the blood, for example.
  • However, the methylation changes did correlate with increased levels of two inflammatory signaling proteins, IL-6 and sTNFR2, that have been associated with fatigue in breast cancer survivors.
  • Many chemotherapeutic agents are effective precisely because they damage DNA in cancer cells.
  • While it was well known that chemotherapy induces epigenetic changes in cancer cells, this is the first study to identify epigenetic changes induced by chemotherapy in non-cancerous cells of the blood.

For more information:  Science Direct, Epigenetic changes associated with inflammation in breast cancer patients treated with chemotherapy,

7.  Adjuvant chemotherapy improved outcomes after isolated locoregional breast cancer recurrence

  • Isolated locoregional recurrences of breast cancer often are associated with increased risk for distant metastasis and breast cancer-specific mortality, according to background information in the study.
  • Researchers conducted the current study to assess whether adjuvant chemotherapy improves outcomes of patients with histologically proven and completely excised isolated locoregional recurrences after unilateral breast cancer. All 162 patients had undergone a mastectomy or lumpectomy with clear surgical margins.
  • At median follow-up of 4.9 years, fewer patients assigned chemotherapy experienced DFS events (28% vs. 44%). Five-year DFS was 69% among those assigned chemotherapy and 57% among those who did not receive chemotherapy (HR=0.59; 95% CI, 0.35-0.99).
  • Researchers found adjuvant chemotherapy was significantly more effective in women with ER-negative isolated locoregional recurrences (P=.046), but the differences in DFS based on ER status of the primary tumor were not statistically significant (P=.43).

For more information:  Lancet Oncol. 2014;doi: 10.1016/S1470-2045(13)70589-8,  Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial

8.  Chemo for Breast Cancer: Timing May Matter

  • Some women with more advanced stages of breast cancer might experience worse outcomes when chemotherapy after surgery is delayed, according a retrospective single-center review of 6827 patients with stage I to III disease.
  • However, overall, there were no differences in outcomes when women (at any disease stage) started chemotherapy 0 to 30 days after surgery, 31 to 60 days after surgery, or more than 60 days after surgery.
  • The outcomes evaluated were overall survival, relapse-free survival, and distant-relapse-free survival.
  • In patients with stage III disease, starting chemotherapy more than 60 days after surgery had a detrimental effect on relapse-free, distant-relapse-free, and overall survival.
  • Furthermore, patients with triple-negative disease and patients with HER2-positive disease treated with trastuzumab (Herceptin, Genentech/Roche) had worse overall survival when chemotherapy was started 60 days or more after surgery.
  • The problem is that no one knows whether delaying the treatment is harmful. “It is unclear whether a delay in initiation of therapy is associated with adverse outcomes,” the authors note.

For more information:  Journal of Clinical Oncology, doi:10.1200/JCO.2013.49.7693 JCO  March 10, 2014 vol. 32 no. 8 735-744 , “Clinical Impact of Delaying Initiation of Adjuvant Chemotherapy in Patients With Breast Cancer”

9.  RBP2, regulator of gene expression responsible for the progression of breast cancer

  • Yale Cancer Center researchers have identified a regulator of gene expression that is responsible for the progression of breast cancer and its metastasis to the lung. The study appears online in Cell Reports.
  •  The Yale researchers analyzed gene expression datasets of human breast tumors, as well as those of cancer cells, and found that overexpression of the enzyme RBP2 is critical for breast cancer metastasis to the lung. Loss of RBP2, they also found, suppressed tumor formation in mouse models.
  • The authors say their evidence suggests that RBP2 regulates a critical epigenetic switch that sets the stage for tumor metastasis. They say the enzyme offers a novel target for development of therapies designed to inhibit tumor progression and metastasis.

For more information:  Cell Reports, 10.1016/j.celrep.2014.02.004, Histone Demethylase RBP2 Is Critical for Breast Cancer Progression and Metastasis

10.  Study identifies TAZ gene important to aggressive breast cancer development


Just call me TAZ. Image credit: wikipedia

  • In cancer, normal cells can become unpredictable or aggressive and thus difficult to treat with anti-cancer drugs. By identifying the genes responsible for this change in cells from breast tissue, researchers hope to identify a way to stop or reverse it.
  • In breast tissue, there are two main types of cells: luminal cells and basal cells. Normally luminal cells are “programmed” by a particular class of proteins (transcription factors), which prevent them from becoming basal cells, and vice-versa.
  • Previous work led by Charlotte Kuperwasser, principal investigator, determined that some common forms of breast cancer originate from luminal cells while some rarer forms of breast cancer originate from basal cells.
  • The research team identified a gene, TAZ, which controls whether breast cells behave more like basal cells or more like luminal cells, information that might be important in understanding and potentially treating certain difficult-to-treat forms of breast cancer.
  • TAZ helps to regulate how different genes operate in different cell types.
  • Results: The research team found that the experimental group had an imbalance of cell populations in breast tissue: too many luminal and too few basal. The control group had a normal ratio of luminal to basal cells. In breast tissue from women with cancer, they found high levels of TAZ in basal but not luminal tumors.

For more information:  Cell Reports, 10.1016/j.celrep.2014.02.038, The Hippo Transducer TAZ Interacts with the SWI/SNF Complex to Regulate Breast Epithelial Lineage Commitment


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