Sunday, 1 January 2017

Talk : Breast Cancer - A Researcher's Perspective

The University of Nottingham recently hosted Professor Stewart Martin from the School of Medicine for a public lecture on "Breast Cancer - A Researcher's Perspective". @Gav Squires was there and has kindly written this guest post summarising Prof Martins talk.(NB: some images sourced by NSB, text slightly edited)

The city of Nottingham has an international reputation for its work on breast cancer. The Nottingham Grading System is the international gold standard for the classification of breast cancer. Meanwhile, the Nottingham Prognostic Index is one of the most effective systems for clinical decision support in routine clinical management - it dictates the best support. The first blood test to detect lung cancer was developed in Nottingham and now a similar test is in development for breast cancer. Over the next two years a major breast cancer research centre will be built in Nottingham.

UoN Medical School (source)

Breast Cancer Incidence and Survival Rates
Around two thirds of women who get breast cancer will survive for 21 years or more, 80% survive for 10 years or more and 95% survive for at least a year. This is despite a growing incidence of breast cancer. There are around 15,500 breast cancers diagnosed every year. This leads to around 1,300 lives being saved although 4,000 are over-diagnosed. In the UK, 120,000 women will lose their lives over the next decade and 10,000 women die globally every week. Breast cancer is the most common form of cancer in women. In addition there are 350-400 cases in men each year.

Breast cancer incidence by age in women (UK) 2006-08 (by Mikael Häggström)

Breast Cancer Development
Breast cancer can either occurs in the breast ducts or the lobules but it is more common in the ducts and it happens when normal cells start behaving abnormally.

Early Stage (Stage 1) invasive cancer is where it hasn't spread beyond the breast or the lymph nodes on the same side of the body.

Locally Advanced (Stage 3) is when it still hasn't spread but is bigger than 5cm across and growing into the skin or muscle of the chest and/or much lymph node involvement.

Metastatic (Stage 4) cancer is where it has spread to other parts of the body such as the liver or bones.

Of around 700 patients annually in Nottingham, only 10% are at the locally advanced stage - a tribute to the screening programmes.

How Cancer Spreads (By Jane Hurd )

The Nottingham Prognostic Index
This index looks at three measures of the cancer:

• How big?
• How aggressive?
• How much nodal involvement?
Patients are stratified into three groups - those with a poor outlook, those with an average outlook and those with a good outlook.

Cancer Treatment
There has been an explosion in how you can map cancers at the molecular level. It turns out that there are between 15 and 20 types of breast cancer and these fit into four main classes - Luminal A, Luminal B, HER2+ and Triple Negative. Hormone therapy can help with Luminal cancers, while molecular techniques can help with HER2+. Triple Negative cancers are treated with traditional therapies such as chemotherapy.

Around 50% of breast cancers are Luminal A and these have the best prognosis. 15-20% are Triple Negative and these have the worst prognosis. Around 10% of cases are HER2+ and the remaining are Luminal B.

There are currently three big gaps in breast cancer research. The first is early detection. At the moment, only women over 47 can get a mammogram. So, the plan is to try and develop a blood test. The second is trying to stop the cancer spreading - discover why is spreads and find ways to stop it. Finally, the need to treat it right - develop targeted treatments for each patient and develop ways to improve conventional treatments.

Blood Test Samples (by GrahamColm)

Cancer Break Up is Bad
When the primary cancer breaks up and makes its way around the body, the survival rate drops. Blood vessels feed the cancer and allow it to get bigger. Meanwhile, lymphatic vessels help to drain the cancer. Ten years ago it was thought that cancer was metastised through the blood vessels. New technology has allowed scientists to differentiate between blood vessels and lymphatic vessels. You don't see that many lymphatic vessels in a cancer but there are a lot of blood vessels. So we expect to see many more cancer cells in the blood vessels but actually 97% of the invasion is in the lymphatic vessels. It invades these vessels because it is easier to migrate and it also causes the immune system to act differently.

Prof Martin (via @GavSquires)

Cancer Mortality (Mikael Häggström, using using reference:Jemal A, Siegel R, Ward E et al. (2008). "Cancer statistics, 2008")

Calpastatin and Calpain
Decreased levels of the protein calpastatin leads to increased levels of one of more of the calpain protein family, which allow cells to start migrating. Patients with triple negative breast cancer (the most dangerous type) have significantly worse prognosis if their tumours have high expression of calpain-2. Calpain also seems to pay a role in regulating therapeutic response - women resistant to certain treatments have high levels of caplain-1. So, looking at caplain levels helps with prognosis and by targeting it, treatment can be improved and the spread of cancer can be stopped.

Calpain (by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute

Radiotherapy uses high-energy radiation to treat cancer. It increases oxidation stress but cancer cells often have increased anti-oxidants which could decrease the treatment’s effectiveness.

Can we do something to improve this treatment? Yes, one family of proteins stands out - if we can target these proteins we can improve the treatment. Unfortunately, it takes a long time to test the drugs that could have an impact. However, it seems that metformin, a treatment for diabetes that is over 50 years old, can make radiotherapy 100 times more effective in certain cancers.

Metformin (source)


Life Cycle 6 Fundraiser

The public lecture series returns on 19th January at 6pm in Lecture Theatre B1 at the School of Physics and Astronomy where Claire Sycamore will talk about "Thinking Outside the (Pill) Box: Alternative Drug Delivery Strategies" For more information visit:

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