Study gives insight into breast cancer recurrence

November 5, 2014
Mammograms showing a normal breast (left) and a cancerous breast (right). Credit: Wikipedia.

Work by University of Manchester scientists has explored what allows some cases of Ductal Carcinoma in Situ (DCIS), a non-invasive form of breast cancer, to resist treatment and come back, as well as identifying a potential new target to improve the effectiveness of radiotherapy.

Around 5,000 cases of DCIS, a condition where cancerous cells are contained within the milk ducts of the breast, are diagnosed each year in the UK, with two thirds diagnosed through breast screening. If left untreated, up to half of DCIS cases could progress into invasive breast cancer, but it is not possible to say which ones, so all women are offered treatment.

This usually involves breast-conserving surgery (lumpectomy) and, to reduce the risk of the cancer returning, radiotherapy to kill any remaining cancer cells.

However, even with treatment up to one in five patients will see their DCIS come back, either as DCIS or as invasive breast cancer.

Now researchers from The University of Manchester and University Hospital of South Manchester NHS Foundation Trust - both part of the Manchester Cancer Research Centre - have investigated the role of a molecule known as FAK in controlling the resistance of DCIS to radiation and in predicting disease recurrence.

Dr Gillian Farnie, whose work at the University's Institute of Cancer Sciences was funded by a five-year £500,000 Breast Cancer Campaign Scientific Fellowship, said: "We know that cancer stem cells are able to avoid or repair damage caused by treatment. We wanted to look at how FAK is involved in this treatment resistance."

The team found that cancer cell samples containing more cancer stem cells had increased levels of FAK and that these samples were better able to survive radiotherapy. By examining patient tissue samples and information about whether each person had had a recurrence, the scientists discovered that high FAK activity was linked to the disease returning, either as DCIS or invasive breast cancer.

In further work, a drug that blocks FAK reduced the formation of mammospheres, or clumps of breast cancer stem cells, showing FAK is important in activity. By combining this inhibition of FAK with radiotherapy, the group was able to achieve a greater treatment effect than with either therapy alone.

To see if the FAK drug works in more complex living systems, the researchers gave mice with DCIS a treatment to block FAK. In treated mice the DCIS were less likely to turn into invasive-like cancer cells showing FAK is important in the progression of DCIS to invasive cancer.

"We have shown that blocking the activity of FAK not only reduces the growth of breast cancer stem cells, but also improves sensitivity to radiotherapy. Our findings suggest we can reduce the likelihood of DCIS recurring by inhibiting FAK and measuring FAK levels could offer a method to predict which patients are most likely to experience recurrence," added Dr Farnie.

Katherine Woods, Research Communications Manager at Breast Cancer Campaign, said: "There is still so much we don't know about DCIS. It is vital that we get a better understanding of the biology of DCIS as well as what makes it return in some women and become .

"This knowledge could help doctors avoid over-treating those patients whose DCIS won't come back, while making sure treatment is working for women who need it. Dr Farnie's research is an important step in this direction, and we are excited to see how the next stages progress.

"Dr Farnie and colleagues have also provided further evidence that cancer stem cells seem be helping cancers to survive . This is a fascinating new field of thought in research, especially given the team's findings that we might be able to stop cancer by blocking the molecule FAK."

Explore further: New findings could tackle over-diagnosis and over-treatment of breast cancer

More information: The paper "'Focal adhesion kinase and wnt signalling regulates human ductal carcinoma in situ stem cell activity and response to radiotherapy' was published in Stem Cells DOI: 10.1002/stem.1843

Related Stories

New findings could tackle over-diagnosis and over-treatment of breast cancer

December 4, 2013
New research from Queen Mary University of London has revealed, for the first time, the molecule αvβ6 (alpha v beta 6) could tell doctors which cases of Ductal Carcinoma in Situ (DCIS), a condition where non-invasive cancerous ...

Breast conserving treatment with radiotherapy reduces risk of local recurrence

September 18, 2013
Results of EORTC trial 10853 appearing in the Journal of Clinical Oncology show that breast conserving treatment combined with radiotherapy reduces the risk of local recurrence in women with ductal carcinoma in situ (DCIS). ...

New drug target can break down cancer's barrier against treatment

July 27, 2014
Cancer research UK scientists at Barts Cancer Institute have found that targeting a molecule in blood vessels can make cancer therapy significantly more effective, according to research published in Nature.

Effective treatment for DCIS is vital for continued reduction in Australia's breast cancer mortality rate

August 18, 2014
Variations in the treatment of DCIS (Ductal Carcinoma In Situ or precancerous cells of the breast) may be a contributing factor in worldwide differences in breast cancer mortality rates according to Professor John Boyages, ...

New skin gel fights breast cancer without blood clot risk

July 15, 2014
A gel form of tamoxifen applied to the breasts of women with noninvasive breast cancer reduced the growth of cancer cells to the same degree as the drug taken in oral form but with fewer side effects that deter some women ...

Terminology used to describe preinvasive breast cancer may affect patients' treatment preferences

August 26, 2013
When ductal carcinoma in situ (DCIS, a preinvasive malignancy of the breast) is described as a high-risk condition rather than cancer, more women report that they would opt for nonsurgical treatments, according to a research ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.