Researchers develop Potential New Treatment Approach for Breast Cancer

 

Irish cancer researchers have developed a potential new treatment approach for a form of breast cancer, which can be difficult to treat.

The Opens in new windowBREAST-PREDICT researchers at RCSI focused on a form of cancer that affects around one in eight breast cancer patients.

The type of cancer targeted – invasive lobular breast cancer – has been understudied to date, leaving patients without tailored treatment options. The discovery in the paper is now paving the way for more personalised treatment of this form of cancer.

Dr Louise Walsh, joint author of the paper with Dr Kathryn Haley, was supervised by Professor Darran O’Connor and Dr Tríona Ní Chonghaile in RCSI. Opens in new windowIrish Cancer Society and Opens in new windowBreast Cancer Now funded the paper, which is published in Opens in new windowClinical Cancer Research.

Speaking on the discovery, Dr Walsh said: “To know the long hours I spent in the lab have identified novel research findings that will hopefully ensure a better treatment path for patients with this cancer is incredible.

“I’m proud to have played a role in discovering a potential way to target this cancer and improve outcomes for patients in the future. No one is unaffected by cancer in Ireland, but research is the tool we have to ensure that more people can overcome a cancer diagnosis in their life.”

This potential new treatment, a combination approach that comprises two different drugs, blocks molecules in breast cancer cells that control cell growth and survival. The researchers suggest that this treatment approach may be useful for patients who no longer respond to standard therapies. The team are now in the final stages of testing this treatment in the laboratory, supported by additional funding from the Opens in new windowSusan G. Komen’s Foundation, before they hope to advance to clinical trial stage.

Invasive lobular breast cancer accounts for roughly one in eight newly diagnosed breast cancer cases. When caught early, treatments with surgery, radiotherapy and/or chemotherapy can be effective, but this type of breast cancer can be more difficult to detect at these early stages. As the cancer advances, it can spread to other organs and become resistant to chemotherapy and hormone therapy.

The new findings were unveiled today as the Irish Cancer Society urges the public to get involved in Opens in new windowCups Against Breast Cancer, a fundraising campaign which aims to raise money for breast cancer research and support services for people affected by breast cancer.

Head of Research at the Irish Cancer Society, Dr Robert O’Connor, said: “New treatment options for this cancer subtype are urgently needed, so this discovery is hugely important for patients who might benefit from a tailored approach to their treatment.

“This research is an example of the vital work of BREAST-PREDICT, made possible by the country’s support of fundraising campaigns like Cups Against Breast Cancer. This October, members of the public can help fund more lifesaving cancer research and free services for people affected by breast cancer by hosting a coffee morning on 11 October.”

Irish Team to Investigate Metatastic Breast Cancer

Prof Leonie Young of the RCSI

Dublin-based scientists have been awarded funding to investigate how breast cancer tumours spread to the brain.

Almost 2,800 women are newly diagnosed with breast cancer every year in Ireland, and while survival rates have increased, if the breast tumours begin to spread to other parts of the body, which is known as secondary or metastatic breast cancer, the disease becomes incurable.

Almost all of the 700 women who die as a result of breast cancer in Ireland every year have experienced their cancer spreading. The brain is a common place for the disease to spread to and these secondary tumours can be very aggressive.

They can have a big impact on quality of life, due to symptoms such as headaches, seizures, mood/behaviour changes, vomiting and uncoordinated movement.

One challenge that scientists face when treating breast cancer that has spread to the brain is how to develop drugs that can cross the brain’s security network – the blood-brain barrier. This acts as a protective filter, preventing harmful substances from reaching the brain, but it can also filter out useful drugs, meaning treatment options are limited.

However, scientists at the Royal College of Surgeons in Ireland (RCSI) have now been awarded over €200,000 by the UK’s largest breast cancer charity, Breast Cancer Now, to investigate this area further.

They recently discovered that genetic switches that activate the protein, RET, are very common in breast cancer tumours that have spread to the brain, suggesting that they may have a key role to play.

With this new funding, Prof Leonie Young, Dr Damir Varešlija and the Endocrine Oncology Research team in the RCSI, aim to uncover the exact role of RET in the spread of breast cancer to the brain.

They plan to grow cells in the lab and then investigate how silencing the gene that produces RET, or blocking RET itself, may affect breast cancer cells’ ability to spread.

Their tests will involve mice, however as similar drugs are already being evaluated to treat lung and thyroid cancers, it is hoped that RET-blocking drugs could be accelerated into trials for breast cancer that has spread to the brain.

It is hoped that successful trials could help to improve and prolong the lives of those living with metastatic breast cancer.

“Brain metastases truly represent an unmet need in current cancer care which urgently needs more investment. Having our research funded by Breast Cancer Now will allow us to pursue what is promising to be a very intriguing target that could potentially stop breast cancer cells from spreading to the brain in the first place,” Dr Young explained.

This research was described as ‘vital’ by Breast Cancer Now director, Dr Simon Vincent.

“Professor Young’s vital research could pave the way for trials of new treatments to control breast cancer that has spread to the brain. Not only is secondary breast cancer incurable, but when tumours spread to the brain, the side-effects can be extremely debilitating. We urgently need to develop new treatments to give these patients more time to live, and to help improve their quality of life,’ he commented.

Breast Cancer Now currently supports almost 380 researchers at 31 institutions across the UK and Ireland.

By Deborah Condon for IrishHealth.com. Read full article here.

Irish Researchers Find Vitamin D Link to Breast Cancer Survival

The study’s findings do not take account of other important factors like the patients’ diet and exercise. Photograph: Christopher Furlong/Getty Images
The study’s findings do not take account of other important factors like the patients’ diet and exercise. Photograph: Christopher Furlong/Getty Images

Brian Hutton for The Irish Times

Breast cancer patients taking vitamin D supplements after being diagnosed were found to have better survival rates, a study of thousands of Irish women by cancer researchers has found.

Both the Royal College of Surgeons in Ireland (RCSI), which led the research, and the Irish Cancer Society (ICS) say the findings are significant but stress they do not take account of other important factors like the patients’ diet and exercise.

Dr Robert O’Connor, head of research at the ICS, sounded a note of caution.

“Before rushing out to buy vitamin D supplements, we urge women with breast cancer to first talk to their medical team,” he said.

“Vitamin D use can cause health issues and each woman’s cancer is unique and will require personalised treatment.”

The researchers looked at anonymised data on the pharmacy purchases of almost 5,500 Irish women with breast cancer, aged between 50 and 80, in the years between 2000 and 2011.

The information was provided by the National Cancer Registry of Ireland.

They found those taking a vitamin D supplement had a 20 per cent increased survival rate compared to those who did not.

Dr O’Connor said the findings, published in the journal Breast Cancer Research and Treatment, were preliminary and only show an association.

“We will only know if vitamin D supplementation should be recommended to improve breast cancer treatment outcome in the coming years when the results of clinical trials emerge,” he said.

Researchers did not know anything else about the women that could possibly impact on their survival rates, such as physical activity and a healthy diet, which can both help a patient undergoing cancer treatment.

The research also found vitamin D users to be generally younger, less likely to smoke and have lower tumour stage and tumour grade progression compared to those who didn’t take the supplement.

These are all factors more likely to be associated with better survival.

The research was led by RCSI researcher Dr Jamie Madden, under the supervision of Prof Kathleen Bennett, associate professor in Pharmacoepidemiology at the RCSI.

Ms Bennett said previous studies have found that higher blood levels of vitamin D, which can come from diet, sunlight or supplements, is associated with increased breast cancer survival.

“Our study suggests that vitamin D supplementation might be useful for women diagnosed with breast cancer,” she added.

“Large clinical trials are already underway overseas to look into this further.”

The findings were published as the ICS launched its Cups Against Breast Cancer fund-raising campaign in Dublin’s St Stephen’s Green.

More than 3,100 women in Ireland are diagnosed with breast cancer every year. It is the second most common cancer affecting women.

Four in ten of those diagnosed are aged between 50-64 but younger women are also affected, with just under a quarter of newly-diagnosed women aged aged under 50.

Survival rates are improving. Some 83 per cent of those with a breast cancer diagnosis now live more than five years.

Irish Scientists Make Major Breakthrough in Breast Cancer Research

Potential drug identified by NUIG team that reduces cancer and helps improve treatment

Kevin O’Sullivan

Breast cancer clusters growing in 3D: Photo: NUI Galway
Breast cancer clusters growing in 3D: Photo: NUI Galway

Irish scientists have identified why there is a high relapse rate after chemotherapy in women who have the most aggressive form of breast cancer.

The breakthrough has enabled the researchers at NUI Galway to develop a drug with potential for clinical use, which not only improves the effectiveness of the initial chemotherapy treatment but also reduces relapse among women with this form of cancer.

Up to now, triple negative breast cancer (TNBC) is one of the most aggressive and difficult to treat. It accounts for around 15 per cent of all breast cancers diagnosed and occurs more frequently in younger women.

Scientists, led by Prof Afshin Samali, director of the Apoptosis Research Centre at NUIG, identified an impairment of the “normal stress response” of healthy cells as the critical factor.

They found that targeting a “stress response pathway”, known as IRE 1, may improve the response to chemotherapy and reduce relapse for patients with TNBC. Their findings were published on Wednesday in the journal Nature Communications.

“Unlike other forms of breast cancer, there are no targeted therapies available for triple negative breast cancer,” Prof Samali explained. Currently, chemotherapy is the mainstay treatment, and although initially successful, a large percentage of TNBC patients relapse within one to three years of treatment and have a poor long-term prognosis.

The “molecular basis” (exact mechanism) of tumour relapse post chemotherapy remained unknown until now, he said. The research team has “shown for the first time that IRE1, which is a cellular stress sensor that normally acts to alleviate short-term stresses within cells – such as lack of nutrients or oxygen – is a central driver of treatment-related relapse”.

The team discovered that chemotherapy can activate “the IRE1 stress response” in TNBC cases, leading to the production of “survival signals” that are pumped out of the cell to support the growth of new cancer cells.

New drug reduces relapse

Most importantly, the study showed this process can be halted by specifically inhibiting IRE1 using “a clinically-relevant, small molecule drug called MCK8866” that not only improves the effectiveness of the initial chemotherapy treatment, but also reduces relapse of this aggressive form of breast cancer.

Using TNBC cells treated with chemotherapy, the research team found that blocking IRE1 activity reduced the production of survival signals, and in turn reduced the growth of new cancer cells by 50 per cent.

Furthermore, in laboratory-based experiments, described as “a pre-clinical model of TNBC”, the drug increased the effectiveness of chemotherapy treatment, leading to regression of eight out of 10 cancers compared to regression of just three out of 10 cancers using chemotherapy alone.

“The combination of the MCK8866 drug with chemotherapy also reduced tumour relapse in this pre-clinical model of triple negative breast cancer,” he confirmed.

In addition, an analysis of 595 patient samples revealed TNBC tumours “displayed the highest IRE1 activity compared to other subtypes”, suggesting IRE1 may be of particular importance in TNBC. Combining chemotherapy with IRE1 inhibitors could offer substantial benefits for TNBC patients, they concluded.

Prof Samali added: “This study is the result of extensive laboratory experiments, analysis of breast cancer patient samples, testing pre-clinical models of triple negative breast cancer and collaboration with our international and industry partners.”

Precision oncology

The new era of precision oncology is aimed at tailoring treatments to individual cancer patients, he added. “We are delighted to lead the way in identifying a new therapeutic strategy for TNBC patients who are most in need of better treatment options.

“Furthermore, this strategy may benefit many other cancer patients whose cancer cells rely on activated cell stress responses to survive.”

These pre-clinical trials will pave the way for rapid clinical development of MKC8866. A number of companies work on IRE1 inhibitors and the NUIG scientists anticipate such inhibitors will be tested in human clinic trials in two to three years.

Dr Susan Logue, first author of the study, said: “This work has uncovered a previously unknown role for IRE1 and suggests that it may represent a good therapeutic target for the treatment of triple negative breast cancer.

“While further research is needed, this work is a great example of how curiosity-driven basic research can lead to translational outcomes with real potential to impact on patient treatment.”

The study was funded by Science Foundation Ireland; the Irish Cancer Societyand Horizon 2020 – with initial funding from Breast Cancer Now.

Breakthrough Allows Identification of Resistance to Breast Cancer Treatment

Early detection development by Irish researchers enables different strategy to be put in place

Kevin O’Sullivan

 

Majella O’Donnell at the launch of the Irish Cancer Society’s breast-cancer fundraising campaign “Cups Against Cancer” on Monday
Majella O’Donnell at the launch of the Irish Cancer Society’s breast-cancer fundraising campaign “Cups Against Cancer” on Monday

Irish researchers have developed a way of identifying women with breast cancer who are likely to be “resistant” to some of the most common treatments for the disease.

Their breakthrough comes with the potential to identify such patients more quickly, and in turn develop treatments that increase survival rates.

Prof Leonie Young and Dr Sara Charmsaz of the Royal College of Surgeons in Ireland outlined details of their research at an Irish Cancer Society event to launch a new fundraising drive to fund further scientific work by the Breast-Predict group, which includes the RCSI and five other Irish universities.

The RCSI team with Beaumont Hospital surgery department have found a new way to monitor the treatment of oestrogen-positive (ER-positive) breast cancer patients. Women with this form of cancer, which is one of the most commonly diagnosed, usually take drugs such as Tamoxifen or Aromatose inhibitors to reduce the chances of the cancer coming back.

Some of these patients, however, can become resistant to these treatments and their cancer returns. The team discovered that ER-positive women with a high level of a “biomarker” called S100Beta in their blood and “are significantly more likely to see a recurrence of the disease”.

“The early detection of patients with treatment resistance enables a different strategy to be put in place which can significantly improve there patients’ survival,” explained Prof Young.

Clinical trial

The next stage is for this research to undergo a clinical trial, Dr Charmsaz told The Irish Times. This would, it is hoped, lead to new monitoring strategies which could increase survival of patients, she added. Identifying women in this category quicker would mean that the cancer would be treated before metastasis, when it has spread to other parts of the body.

TV star Majella O’Donnell, who is married to singer Daniel O’Donnell, paid tribute to the researchers and underlined the need for ongoing funding to reduce the incidence of cancer and provide more effective treatments. She was speaking at a launch of the cancer society’s “Cups Against Cancer” campaign which is being staged during October, where members of the public are being asked to host a coffee morning and raise funds for the society.

Four years on from her own encounter with breast cancer, she said eight Irish women a day continue to be diagnosed with the disease. While treatments had improved, “research is the only way to address this”.

She added: “When I found out I had breast cancer I was shocked. The treatment was tough and it was difficult emotionally. Thankfully there are a lot of supports available and more advances are being made as a result of cancer research, which is improving outcomes.”

Phenomenal reaction

She described the constant worry of “looking over the shoulder” to ensure the cancer had not returned. But she had learned to relax and go in and get the reassurance of her oncologist when it was needed. Her appearance on the Late Late Show had prompted a phenomenal reaction, especially “a sharing of support and learning from other people” – it also helped raise more €700,000 for the society.

Her advice to women recently diagnosed was to “take each day at a time” and not to avail of “Dr Google” though human nature was such that searching for information through that source was understandable in the circumstances.

Cancer society head of fundraising Mark Mellett said the “Cups Against Cancer” campaign would enable researchers to continue to find better ways to diagnose and treat this disease, and ensure women were supported “through such a frightening and worrying time”.

QUB and Almac Group in New Breast Cancer Discovery

Almac Group’s Diagnostics business, in collaboration with Queen’s University, has announced the identification of a novel immune response mechanism in breast tumours deficient in DNA repair.

The study has been published in the Journal of the National Cancer Institute (JNCI).

The publication entitled ‘Activation of STING-Dependent Innate Immune Signalling By S-Phase-Specific DNA Damage in Breast Cancer’ follows on from Almac’s previous publication of a 44 gene immune based assay capable of prospectively identifying breast cancer patients with a defect in the FA/BRCA pathway who benefit from anthracycline based chemotherapy.

The current study explains the molecular basis of this 44-gene immune based assay and demonstrates that the genes in the assay reflect activation of the innate immune response cGAS/STING/TBK1/IRF3 pathway in response to DNA damage.

The study is particularly interesting because it provides a clear rationale for the observed link between DNA repair deficiency and activation of the immune checkpoint PD-L1. Almac will now pursue their 44-gene assay as a means of prospectively identifying breast cancer patients likely to respond to PD-L1 targeted therapies.

Dr Eileen Parkes, Academic Clinical Lecturer at the Centre for Cancer Research and Cell Biology at Queen’s said: “This research provides a new way of explaining how immune cells are targeted to certain breast tumours, and could help decide which patients are most likely to respond to this new class of immune therapies. Approximately one third of breast cancers will have this immune-rich picture, therefore a huge amount of patients could benefit from this research.”

Professor Richard Kennedy, MD, PhD, McClay Professor in Medical Oncology at Queens and VP and Medical Director, Almac Diagnostics commented: “The study provides strong justification for the underlying biology that causes enhanced PD-L1 expression. Almac will now engage with pharma and academia to investigate the potential clinical benefit for predicting response to immune checkpoint inhibitors, such as PD-L1 and IDO1 and their use in combination with DNA damaging agents.”