NHS Choices

Aggressive breast cancer protein discovered

NHS Choices - Behind the Headlines - Mon, 07/07/2014 - 12:30

"A breakthrough by scientists could lead to a new treatment for one of the most aggressive forms of breast cancer," the Mail Online reports. Researchers have identified a protein called integrin αvβ6, which may help trigger the spread of some types of breast cancer.

Up to a third of breast cancers are HER2-positive cancers. These are cases of breast cancer where growth is driven by a protein called human epidermal growth factor receptor 2 (HER2). These types of cancer can be particularly aggressive.

Seventy percent of people with HER2-positive breast cancers develop resistance to Herceptin, the main drug treatment for these cancers, effectively leaving them with no treatment options.

This laboratory study examined samples of breast cancer tissue from two cohorts of women with breast cancer. Researchers looked at the expression of a protein called integrin αvβ6, which has been shown to interact with HER2 to stimulate cancer growth.

The researchers found women who had higher expression of integrin αvβ6 in their breast cancer tissue had poorer five-year survival rates, particularly when they were also HER2 positive.

The researchers then studied mice that had been grafted with breast cancer tissue. But a potential new treatment called 264RAD was found to block integrin αvβ6 in the rodents.

Giving this treatment in combination with Herceptin stopped cancer growth, even in breast cancer tissues resistant to Herceptin.

Clinical trials of 264RAD in women with this particularly high-risk type of breast cancer are now required.

 

Where did the story come from?

The study was carried out by researchers from Queen Mary, University of London, and was funded by the Breast Cancer Campaign and the Medical Research Council.

It was published in the peer-reviewed Journal of the National Cancer Institute, and is open access and available to read for free online.

Both the Mail Online and The Daily Telegraph's reporting of the study is accurate and informative.

 

What kind of research was this?

This was a laboratory study examining samples of breast cancer tissue from two cohorts of women with breast cancer. Researchers looked for the expression of a particular protein called integrin subunit beta6 (integrin αvβ6). They then looked at how the expression of this protein was associated with cancer survival.

The researchers explain that in up to a third of all breast cancers, a particular protein called human epidermal growth factor receptor 2 (HER2) is overexpressed. This is associated with a very aggressive breast cancer.

These cancers are aggressive because HER2 triggers signalling pathways that stimulate breast cancer cells to grow out of control. This means the cancer cells are more likely to spread into the lymph nodes or to other major organs of the body (known as metastases or metastatic cancer).

Currently, some HER2-positive breast cancers can be treated using the biological antibody treatment Herceptin (trastuzumab). Herceptin works by binding to the protein receptors and blocking them so HER2 cannot stimulate the growth of the breast cancer cells.

However, as the researchers point out, more than 70% of people have developed resistance to Herceptin, leaving them without other treatment options. New treatments are therefore needed for people with HER2-positive breast cancers.

A molecule called TGFβ has been shown to promote HER2-driven cancer by increasing the migration, invasion and spread of breast cancer cells. Integrin αvβ6 has been identified as an activator of TGFβ and implicated in promoting the growth of various types of cancer.

With this knowledge, this research aimed to see whether integrin αvβ6 could influence HER2-positive breast cancer and if inhibiting its action helped reduce the cancer size and spread.

 

What did the research involve?

The research included two cohorts of people with breast cancer:

  • a Nottingham cohort that included 1,795 consecutive women treated from 1986 to 1998
  • a London cohort that included 1,197 women mostly treated from 1975 to 1998

The researchers were able to gather complete information on the women's tumour types, including whether they were HER2 positive.

They examined tissue samples for the expression of integrin αvβ6 and looked at how this was associated with survival by seeing whether the women were still alive at five-year follow-up checks.

The researchers also looked at survival rates when there was co-expression of both HER2 and integrin αvβ6.

Further laboratory experiments using mice grafted with breast cancer tissue examined treatment options using Herceptin (trastuzumab), the antibody known to block HER2, and an antibody called 264RAD, which was found to block integrin αvβ6.

 

What were the basic results?

High expression of integrin αvβ6 was found in 15-16% of breast cancer tissue samples from the two cohorts of women.

The researchers found a significant association between the expression of integrin αvβ6 and survival.

In women with a high expression of integrin αvβ6, five-year survival dropped from 75.6% to 58.8% in the London cohort, and from 84.1% to 75.0% in the Nottingham cohort.

In statistical terms, this meant that high expression was associated with an almost doubled risk of mortality.

Even with adjustment for tumour stage, size and grade, integrin αvβ6 was an independent predictor of overall survival.

For the Nottingham cohort, the researchers also had data available on distant spread (metastases) – 39.5% of those who were integrin αvβ6-positive had metastases, compared with 30.9% who were integrin αvβ6 negative.

When looking at co-expression of both integrin αvβ6 and HER2, they found this combination was associated with a particularly poor prognosis. In women who were HER2 positive, five-year survival was 65.1%, but it dropped to 52.8% if integrin αvβ6 was also strongly expressed.

The studies in mice grafted with human tumour tissue found both Herceptin and the study molecule 264RAD individually slowed tumour growth, but the combination of the two effectively stopped tumour growth, even in breast cancer tissues resistant to Herceptin.

 

How did the researchers interpret the results?

The researchers conclude that the overexpression of integrin αvβ6 in breast cancer is a poor prognostic factor associated with lower survival and the development of distant metastases.

They say the overexpression of both integrin αvβ6 and HER2 is associated with an even poorer prognosis.

The researchers feel the likely biological explanation is integrin αvβ6 and HER2 co-operate within the same molecular complex and integrin αvβ6 mediates the invasive behaviour of HER2-positive cancer.

They suggest targeting αvβ6 using the antibody 264RAD, either alone or in combination with Herceptin, may provide a novel therapy for people with this very high-risk breast cancer sub-type (HER2/αvβ6 positive), particularly if it is resistant to Herceptin.

 

Conclusion

This is a valuable laboratory study that furthers our understanding of the way HER2 may promote the growth, proliferation and spread of breast cancer cells, possibly through the influence of the protein integrin αvβ6.

The researchers suggest up to 40% of people with HER2-positive breast cancers may also have a high expression of integrin αvβ6.

The discovery that integrin αvβ6 may play a role in mediating the growth and progression of these cancers hopefully opens up new treatment possibilities for people with HER2-positive cancers.

As the researchers suggest, their study supports the proposal that testing breast tissue biopsies for the expression of αvβ6 should become a routine procedure to stratify women with breast cancer into this new very high-risk αvβ6-positive/HER2-positive group.

The laboratory experiments in mice with human breast cancer tissue grafts suggested the combination of Herceptin with the antibody 264RAD could be effective in stopping tumour growth in this group.

However, the development of the 264RAD treatment is still in the very early stages. Clinical trials in people with αvβ6-positive and HER2-positive breast cancer are now awaited. These will tell us whether 264RAD – either alone or in combination with Herceptin – could be an effective treatment option for this very high-risk sub-group.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

New treatment to stop spread of breast cancer: Scientists pinpoint molecule that causes cells to spread quickly. Mail Online, July 4 2014

Breast cancer breakthrough brings hope. The Daily Telegraph, July 4 2014

Links To Science

Moore KM, Thomas GJ, Duffy SW, et al. Therapeutic Targeting of Integrin αvβ6 in Breast Cancer. Journal of the National Cancer Institute. Published online June 30 2014

Categories: NHS Choices

Children’s TV contains unhealthy 'food cues'

NHS Choices - Behind the Headlines - Fri, 04/07/2014 - 13:00

“Children are being bombarded with scenes of unhealthy eating on TV,” The Independent reports. Researchers looking at public broadcasting in the UK and Ireland have found that children’s TV contains a high number of visual and verbal references to unhealthy foods.

In the UK, direct TV advertising of unhealthy food to children has been banned since 2008.

However, the researchers were still interested in whether children’s TV broadcast by state-funded organisations still promotes unhealthy food choices to young children.

Researchers assessed five weekdays of children programmes from the BBC and its Irish equivalent, RTE. They were interested in what they describe as “cues” – visual, verbal and plot-driven references to specific foods and drinks.

Unhealthy foods accounted for just under a half of specified food cues, and sugar-sweetened beverages for a quarter. The context of the food and drink cue was mostly positive or neutral, with celebratory/social motivations the most common.

As the programmes were on non-commercial TV, it could be the case that the inclusion of said cues was due to cultural, and not commercial, reasons.

The plot device of a “slap-up meal” as a reward for a job well done, or as a treat, is a constant in children’s fiction, ranging from Rastamouse to the Famous Five.

Importantly, however, the study can’t tell us whether the food and drink cues directly influence the children’s food and drink requests or their eating patterns.

 

Where did the story come from?

The study was carried out by researchers from the University of Limerick in Ireland and Dalhousie University, in Halifax, Canada. No sources of financial support are reported. 

The study was published in the peer-reviewed medical journal Archives of Diseases of Childhood, and has been released on an open-access basis, so is free to read online.

Overall reporting of the study by BBC News and The Independent is of a good quality.

The BBC includes useful wider debate on the issue, with Malcolm Clark, coordinator of the Children's Food Campaign, saying: “It is disappointing that children’s TV seems to be so tamely reflecting the obesogenic environment we all live in, rather than presenting a more positive vision of healthy, sustainable food.”

An obesogenic environment is an environment that promotes unhealthy food choices, such as a workplace located next to lots of fast food outlets. We discussed obesogenic environments back in March of this year.

A BBC spokesperson defended its content, saying: “We broadcast lots of programmes to promote healthy eating to children and to help them understand where food comes from, with series like I Can Cook, Incredible Edibles and Blue Peter.”

 

What kind of research was this?

This was an observational study that examined the frequency and type of food and drink references contained on children’s TV programmes during five weekday mornings, comparing UK and Irish state-funded television channels.

Previous research has demonstrated how there is an association between child weight and the amount of TV that they watch.

The researchers suggest that this could be due to a combination of greater periods of inactivity, and exposure to food advertising while watching TV.

Advertisements targeted at children are said to be dominated by high-calorie, low nutritional-quality foods, and previous research has associated child TV viewing with consumption of low nutrient-density foods, persuading parents to purchase such food, which leads to the development of poor eating habits.

Direct advertising to children of “junk food” has been banned during children’s programming in the UK since 2008, although many children watch adult programming, such as talent shows and soap operas.

There is also the possibility that non-commercial programming may promote unhealthy food choices.

This study aimed to investigate this by looking at food and drink references in broadcasts aimed at children.

Understanding the influences and patterns on children’s eating habits may help in the development of further measures to improve healthy eating, in addition to targeting the overweight and obesity epidemic. However, this study only provides a small snapshot of food and drink references on child’s TV during a one-week period. It cannot tell us how the many other types of media advertising influence eating patterns, or capture the wider picture of all the lifestyle and environmental factors that are associated with overweight and obesity.

 

What did the research involve?

This research only reviewed the public broadcast channels of the BBC in the UK, and Radio Teilifis Eireann (RTE) in Ireland. These channels were said to be studied as they are “‘public-good’ channels, which aim to inform, educate and empower audiences”.

In July and October 2010, the researchers examined a total 82.5 hours of broadcast on these channels over five weekdays, looking at programmes broadcast between 06.00 and 11.30 on the BBC and between 06.00 and 17.00 on RTE. 

The researchers looked at food or drink references (or cues), defined as “a product being displayed within a food-specific context with potential to be consumed”. Cues were coded by type of product and as healthy or non-healthy (based on the food pyramid).

Healthy foods included breads/grains, cereals, meats, dairy, fruit, vegetables, fish and sandwiches.

Unhealthy foods included fast food/convenience meals, pastries, savoury snacks, sweet snacks/bars, ice cream and candy.

Beverages were coded and grouped as water, juices, tea/coffee, sugar-sweetened or unspecified.

They recorded the context of the cue (e.g. whether it was part of a meal, in the school or home setting, etc), and what motivations and consequences were associated with the food (e.g. as a reward, to relieve thirst or hunger).

 

What were the basic results?

The researchers recorded one food or drink cue every 4.2 minutes, equivalent to 450 on the BBC and 705 on RTE. The total recorded time involving food or drink cues was 4.8% of the total 82.5 hours, covering 3.94 hours and averaging 13.2 seconds per cue.

The most foods most commonly seen could not be grouped into a distinct food group (unspecified, 16.6%), followed by sweet snacks (13.3%), sweets/candy (11.4%) and fruit (11.2%). The most common beverages were also unspecified (35.0%), followed by teas/coffee (13.5%) and sugar-sweetened (13.0%). Unhealthy foods account for 47.5% of specified food cues, and sugar-sweetened beverages for 25%.

Just over a third of the cues were visual, a quarter verbal, and the remainder were visual and verbal combined.

A third of the cues were in the home setting, and in a third of cases, the food or drink was consumed.

Half of the programmes involving food and drink cues involved humans, and half were in animations (human or other). In a quarter of the cases, the motivation for the cue was celebratory/social;  in a quarter, it was to relieve hunger/thirst.

In a third of the cases, the motivation and outcomes associated with the food cue were positive, in half they were neutral, and the remainder were negative.

When comparing the two broadcast channels (only the morning broadcasts when they had data for both), there were significantly more cues on the BBC than the Irish channel; correspondingly, this involved both significantly more healthy cue and unhealthy cues. On RTE, the most common types of foods depicted in 20.5% of cues were unspecified, though on the BBC sweet snacks topped the chart, at 19%.

RTE contained significantly more cues for breads/grains, condiments and breakfast pastries, while BBC had significantly more for fruit, sweet snacks and ice cream. For beverages, it was most commonly unspecified in both countries.

BBC included more visual cues, while RTE had more verbal. BBC also had more animated characters, while RTE had more human. For both countries, the motivation was most often celebratory/social, followed by hunger/thirst. Health was not recorded as a cue motivation on the BBC, while it was in 6.2% of RTE cues.

 

How did the researchers interpret the results?

The researchers concluded that, “This study provides further evidence of the prominence of unhealthy foods in children’s programming. These data may provide guidance for healthcare professionals, regulators and programme makers in planning for a healthier portrayal of food and beverages in children’s television”.

 

Conclusion

This study provides a snapshot of the food and drink cues/references contained in children’s TV programmes on BBC and RTE over five weekdays, totalling 82.5 hours of broadcasting.

The research demonstrates the frequency of cues, the types of food and drink associated, and the motivations for the food cue.

This includes the observation that unhealthy foods accounted for just under half of specified food cues, and sugar-sweetened beverages accounted for a quarter.

The context of the food and drink cue was mostly positive, with celebratory/social motivations the most common.

Importantly, this study can’t tell us whether these food and drink cues actually have any direct influence on a child’s food and drink requests or their eating patterns. While an association between a child’s duration of TV viewing and overweight/obesity has previously been established, this is unlikely to be a result of a single factor, such as exposure to food and drink cues in TV programmes. Other factors – most notably, lack of physical activity while watching TV, and possibly the mindless eating snacks while watching – are likely to have a big influence.

As both BBC and RTE are publicly funded broadcasters, it is unlikely that any unhealthy food cues were included for commercial reasons (notorious examples include the McDonalds “Hamburglar” or “Tony the Tiger”, which was used to sell sugared flakes).

The idea that food is a treat or celebration has long been part of children’s fiction, such as the Famous Fives' “lashing of ginger beer and ice creams”.

It would be interesting to take a broader look at the content across TV channels and over a broader period of time, and also compare the content in programmes targeted at children compared to teenagers and adults.

The food and drinks in this study were categorised into broad groups “healthy” or “unhealthy” groups, but this may not necessarily be the case. For example, healthy foods included breads/grains, cereals, meats, dairy and sandwiches. However, in all of these food groups, you can get many different “healthy” and “unhealthy” versions of each.

Ultimately, while television may be useful as an occasional babysitter, it is no substitute for parenting.

Teaching your child healthy habits at an early age increases the chances that such habits will persist into adulthood.

Read more about encouraging healthy eating in children.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Children bombarded with unhealthy eating messages on TV, experts warn. The Independent, July 4 2014

Children's TV 'packed with junk-food references'. BBC News, July 4 2014

Links To Science

Scully P, Reid O, Macken A, et al. Food and beverage cues in UK and Irish children—television programming. Archives of Disease in Childhood. Published online June 30 2014

Categories: NHS Choices

Headbanging could damage your (Motör)head

NHS Choices - Behind the Headlines - Fri, 04/07/2014 - 12:10

“German doctors are highlighting the dangers of headbanging after a 50-year-old man developed bleeding in the brain following a Motörhead concert,” BBC News reports.

The news is based on a case report in The Lancet about a man who developed a subdural haematoma.

subdural haematoma occurs when a blood vessel in the space between the skull and the brain splits apart. This is a serious condition that can be fatal, so early recognition and diagnosis is essential.

This is only one in a very small number of documented cases of brain blood clots that have been associated with headbanging. However, the incident serves as an important caution that the vigorous activity of headbanging may not always be as harmless as supposed. 

 

What is the story?

This was a case report. A case report usually consists of a particularly unusual set of circumstances.

The case was reported by doctors from Hannover Medical School in Germany and published in the peer reviewed medical journal The Lancet.

They report on a 50-year-old man who presented to their neurosurgery department in January 2013, complaining of a constant and worsening headache for two weeks. He had no history of head injury, but did report headbanging at a Motörhead concert four weeks earlier. He had no other past health problems of note, and clinical examination and blood tests were normal. However, a CT scan of his brain it showed a chronic subdural haematoma on the right side of his brain.

 

What is a subdural haematoma?

Both the media, and to a large extent The Lancet, adopt a somewhat whimsical reporting of the case, which is understandable given the unusual circumstances. However, a subdural haematoma is no laughing matter.

The brain and spinal cord are covered by protective membranes called meninges, which are made up of three layers: an inner layer (pia mater – closest to the brain), middle (arachnoid mater) and outer layer (dura mater – closest to the skull). A subdural haematoma therefore means that there is a blood clot underneath (sub) the dura mater. This means that the bleeding has happened between the middle and outer layers of the meninges.

Usually subdural haematoma occurs as a result of head injury or trauma. For example, there have been cases reported in the media where people have developed a subdural bleed after falling and hitting their head while skiing. The Formula One racing driver, Michael Schumacher, was reported to have developed a subdural haematoma as a result of skiing accident in December 2013, that kept him in a coma for six months.

The actress Natasha Richardson died of a subdural haematoma, the symptoms of which only become apparent several hours after she had a skiing injury.

When the bleed develops, the collection of clotting blood takes up space and puts pressure on the underlying brain, causing symptoms such as headache, nausea and vomiting, and possibly drowsiness, confusion, or loss of consciousness.

Links To The Headlines

Headbanging can cause brain injury, say German doctors. BBC News, July 4 2014

Motörhead fan's vigorous headbanging leaves him with blood clot on the brain. The Guardian, July 4 2014

Motorhead fan's brain bleeds from headbanging. The Daily Telegraph, July 4 2014

Heavy metal lovers beware, headbanging can be bad for you: Motorhead fan suffers blood clot after performing 'violent and rhythmic' movement at concert. Mail Online, July 4 2014

Heavy metal fan suffers headbang brain injury. ITV News, July 4 2014

Headbanging to Motörhead caused fan’s brain to bleed. The Times, July 4 2014

Links To Science

Islamian AP, Polemikos M, Krauss JK. Chronic subdural haematoma secondary to headbanging. The Lancet. Published online July 4 2014

Categories: NHS Choices

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