Best of Breast: news for week ending 12 December 2014

The latest news in breast cancer and cancer, aggregated from Google Alerts, for the week ending 12 December 2014.


Smoking can erase the Y chromosome (on the right) Image credit:

There’s been a gradual but steady rise in the number of immunotherapy articles, featuring cancer vaccines.

I think what people need to realise is that a cancer vaccine is not like a flu vaccine where a one-off will provide cover for that season’s viruses.  A cancer vaccine has to cope with a myriad of different metabolic factors, the state of the patient’s immune system etc.

Often cancer vaccines require a course of vaccines for as long as the person lives. The nature of the beast is that it is different in everyone and it mutates, presenting different faces to evade and disguise itself from the body’s immune system.  Multiple vaccines has to be administered to adapt to this enemy that wears a thousand masks.  If the person is lucky, the immune system will wake up and do the rest.  But if not … there are no guarantees that cancer vaccines will work for everybody.

I visited Prof Nesslehut, the world’s expert in dendritic cell vaccines and other immunotherapies, and was advised that a course of vaccines would start at one per month for six months, then tapering down to three-month and six-month intervals.  Over a five-year period that would add up to about Euro100,000 depending on the variants used.

So personalised immunotherapy that is affordable is yonks away unless you’re lucky enough to get onto a trial.

It’s the start of the 2014 San Antonio Breast Cancer Symposium which means loads of research into breast cancer sub-types and treatments, which this week is heavy on TNBC.

1. Why smoking is a greater risk factor for men than women in developing cancer

  • A team of international scientists have discovered a link between smoking and the loss of the Y chromosome in blood cells.
  • As the Y chromosome is only found in cells in men, the researchers believe these findings could help explain why smoking is a greater risk factor for men developing cancer.
  • Previous research from the team, based at Uppsala University in Sweden, had shown that loss of the Y chromosome in these cells was linked to the disease. Now the team have shown that this loss is linked to smoking.
  • But experts are still unclear as to why loss of the Y chromosome in blood cells is connected with the development of cancer. Some think it could be that immune cells, which have lost their Y chromosome, have a reduced capacity to fight cancer cells.

For more information:  Science journal, Smoking is associated with mosaic loss of chromosome Y, DOI: 10.1126/science.1262092

2.  Tamoxifen has long-term positive effect, study finds

  • The preventative effect of the breast cancer drug tamoxifen is maintained for 20 years, reducing rates of the disease by about 30%, according to a study.
  • The results, presented at the San Antonio Breast Cancer Symposium, revealed that 350 women developed breast cancer in the placebo group compared to 251 of those taking tamoxifen, a reduction in occurrence of 29%. Oestrogen receptor (ER) positive invasive cancer, which account for two thirds of all breast cancers, were reduced by 35%.

For more information:  Lancet Oncology, Vol. 16, No.1, Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial

3.  Metastatic breast cancer: vaccine shows promise in early trial

  • A breast cancer vaccine developed at Washington University School of Medicine in St. Louis is safe in patients with metastatic breast cancer, results of an early clinical trial indicate.
  • Preliminary evidence also suggests that the vaccine primed the patients’ immune systems to attack tumor cells and helped slow the cancer’s progression.
  • The study appears Dec. 1 in Clinical Cancer Research.
  • The new vaccine causes the body’s immune system to home in on a protein called mammaglobin-A, found almost exclusively in breast tissue.
  • The protein’s role in healthy tissue is unclear, but breast tumors express it at abnormally high levels, past research has shown.
  • “If we give the vaccine to patients at the beginning of treatment, the immune systems should not be compromised like in patients with metastatic disease.  We also will be able to do more informative immune monitoring than we did in this preliminary trial. Now that we have good evidence that the vaccine is safe, we think testing it in newly- diagnosed patients will give us a better idea of the effectiveness of the therapy.”

For more information:  Clinical Cancer Research, 1 December 2014, doi: 10.1158/1078-0432.CCR-14-0059, Safety and Preliminary Evidence of Biologic Efficacy of a Mammaglobin-A DNA Vaccine in Patients with Stable Metastatic Breast Cancer

4.  Vaccine found to suppress tumor growth and spreading of breast cancer

  • Researchers from Uppsala University found that a therapeutic vaccine directed against tumor vessels can reduce tumor burden and suppress formation of spontaneous lung metastases in a mouse model for metastatic breast cancer.
  • The target molecule of the immunization strategy is the extra domain-A (ED-A) of fibronectin, a protein domain which is highly selective for the tumor vasculature in the adult.
  • “The vaccination approach we have employed is not prophylactic but therapeutic, meaning that immunity was induced after the onset of tumorigenesis – a scenario that resembles the clinical conditions much more closely than prophylactic immunization studies”
  • The therapeutic effect was significant, despite the aggressive nature of the tumor model.
  • Moreover, the vaccine induced an 80 percent reduction metastasis, which is an important finding considering that a majority of all deaths by cancer are caused by cancer that has spread in the body.
  • A major advantage of the approach is that the target molecule ED-A is present in the majority of solid tumors.

For more information: Oncotarget, October 2014, Therapeutic vaccination against fibronectin ED-A attenuates progression of metastatic breast cancer

5.  Cancer’s Super-Survivors: How the Promise of Immunotherapy Is Transforming Oncology

6.  Bisphosphonates May Prevent Breast Cancer Through HER Proteins

  • Researchers have found bisphosphonates may no longer be used solely for osteoporosis treatment.
  • Mone Zaidi, MD, of Mount Sinai, recently published two articles identifying bisphosphonates as cancer preventers in the cases of breast, lung, and colon cancers.
  • Although a number of HER protein inhibitors exist (such as Herceptin, Tarceva, and Iressa), bisphosphonates are special because they inhibit HER activity even when mutations in the proteins are present.
  • This prevents primary therapy resistance to bisphosphonates, a problem that plagues existing HER inhibitors.
  • The work was motivated by the observation that bisphosphonate users tend to have a lower occurrence of several cancers.
  • The authors believe it is important to investigate bisphosphonate use in cancer patients, as a variety of human cancers express mutated HER proteins.
  • Thirty percent of non-small cell cancers, 90% of colon cancers, and 25% of breast cancers are driven by HER mutations.

For more information:  PNAS, December 16, 2014, vol. 111 no. 50, Repurposing of Bisphosphonates for the Prevention and Therapy of Nonsmall Cell Lung and Breast Cancer” and “Bisphosphonates Inactivate Human EGFRs to Exert Antitumor Actions

7.  Scientists pinpoint a new line of defence used by cancer cells

  • Cancer Research UK scientists have discovered a new line of defence used by cancer cells to evade cell death, according to research published in Nature Communications.
  • The PKCƐ (also known as the Protein Kinase C epsilon) signal pathway, which is used by cancer cells but rarely by normal cells, could be important in targeting some cancer cells as they rely on this pathway to survive.
  • The pathway helps the cancer cells survive by allowing them to untangle and separate their DNA. Cancer cells rely on this signal pathway more than normal cells because their DNA is more jumbled and prone to becoming tangled.
  • Turning off the pathway can trigger cancer cells to self-destruct because the machinery used to untangle the DNA fails, meaning it is torn apart as the cell divides – ravaging and causing huge breaks in the code which lead to the cancer cells’ demise.

For more information:  Nature Communications. doi:10.1038/ncomms6685, “Mitotic catenation is monitored and resolved by a PKCε-regulated pathway

8.  Hypnosis ‘helps breast cancer patients’: Patients put in trance before operations ‘spend less time in hospital’

  • One in five breast cancer patients in Brussels is hypnotised before surgery
  • They are hypnotised by an anaesthetist who talks softly about a chosen topic such as cooking or the beach, before administering a local anaesthetic to numb their breasts.
  • The women do not fall asleep but instead go into a dream-like state.
  • The women who were hypnotised were only given a local anaesthetic – on the presumption that the trance-like state was enough to numb any pain – whereas the others were put to sleep under a general anaesthetic.
  • Hypnotised patients were found to need one less day in hospital to recover
  • Those needing chemotherapy and radiotherapy suffered less side effects
  • Blood tests afterwards having shown improved lymph node function, in patients that were hypnotised.  The gland plays a crucial role in the immune system by acting as a filter for cancer cells.

For more information:  San Antonio Breast Cancer Symposium 2014, Potential benefits of hypnosis sedation on different modalities of breast cancer treatment

9.  Keytruda shrank tumors in triple-negative breast cancer

  • Keytruda, a Merck & Co. drug shrank tumors in about 18.5% of women with an aggressive form of breast cancer in a small clinical trial, an early sign of the potential of immunotherapy to treat breast tumors.
  • Keytruda works by blocking a component of immune-system cells known as PD-1, taking a natural brake off the immune system to fight cancer cells.
  • In an early-stage clinical trial, Merck studied Keytruda in 32 women with advanced “triple-negative” breast cancer, or tumors that didn’t express any of three receptors that can be targeted by certain other drugs.

10.  Bevacizumab Works in Triple-Negative Breast Cancer Subtype

  • New results could potentially reignite interest in the use of bevacizumab (Avastin) in breast cancer, specifically in subtypes of triple-negative breast cancer (TNBC), which is notoriously difficult to treat.
  • The new correlative findings come from the previously reported CALGB 40603 trial, which investigated adding either bevacizumab or carboplatin (Paraplatin) to standard paclitaxel neoadjuvant chemotherapy.
  • Bevacizumab also resulted in improved pCR rates among patients whose cancers expressed high proliferation, low estrogen expression, or TP53 mutation mRNA signatures, “all markers of more aggressive biology,” he explained.
  • In contrast, disease subtype did not affect the positive pCR response seen when carboplatin was added to paclitaxel.

For more information:  San Antonio Breast Cancer Symposium 2014, Final efficacy results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer


Tryptophan is found in turkey


11.  Triple-negative cancer cells use the amino acid, tryptophan, to spread

  • In a new study, researchers with the University of Colorado Cancer Center have found that certain types of cancer cells use tryptophan to survive while moving through the body to create new tumors.
  • When healthy cells become detached from the foundation on which they grow, they are programmed to undergo cell death through a process known as anoikis (“without a home” in Greek).
  • This means that in order to metastasize, cancer cells have to evade anoikis — they have to survive while in suspension, unattached from a foundation.
  • The current study used a gene array to discover which genes were upregulated in triple negative breast cancer cells that were able to grow in suspension compared with cells that were still attached to a substrate.
  • Many of the gene expression changes in the triple negative breast cancer cells that had learned to survive detachment were in a single metabolic pathway — the kynurenine pathway, which is responsible for degrading the essential amino acid tryptophan.
  • The faster the kynurenine pathway, the faster tryptophan is degraded.
  • Controlling the speed of the kynurenine pathway is the enzyme TDO2 — which happened to be the most upregulated gene in detached compared to attached triple-negative breast cancer cells.
  • In other words, it may be that cancer cells over-express TDO2, which speeds up the whole kynurenine pathway, and degrades more tryptophan — all of which helps these cells to escape anoikis, which allows them to survive long enough to pick up roots and move to other places in the body.
  • When a cancer cell detaches and cranks up this catabolic pathway, it can metabolize tryptophan faster and promote survival.
  • Currently, drugs targeting other enzymes in the complex chain of the kynurenine pathway are already in clinical trials.
  • For example the drug indoximod by New Link Genetics is being tested in combination with chemotherapy against metastatic breast cancer. This drug adjusts features within the pathway to help the body’s immune system more effectively target cancer cells.

For more information: San Antonio Breast Cancer 2014, Defining the role of the kynurenine pathway in mediating anoikis resistance in triple negative breast cancer

12.  Targetting heat shock protein can reduce drug resistance in breast cancer

  • US researchers have found that combining conventional hormone therapy with an experimental cancer drug helped overcome drug resistance in breast cancer cells in the lab.
  • The scientists had previously discovered that HSP90 played a key role in how fungus becomes resistant to antifungal medication.
  • ER+ breast cancer growth is powered by the hormone oestrogen and treated with a therapy that tries to stop or block the effects of the hormone.
  • But tumours can become resistant to the medication and HSP90 appears to play a key role in helping this resistance develop.
  • Even a low dose of a drug that blocks HSP90, called ganetespib, helped prevent drug resistance and stopped the tumour cells from replicating in mice.

For more information:  Proceedings of the National Academy of Sciences DOI:10.1073/pnas.1421323111, HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models


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