Beating Breast Cancer

Examining inherited high-risk genes in order to tackle genetic breast cancer.

breast cancer

Breast cancer is the most common cancer in the UK, with an estimated one in eight women at risk of being diagnosed in their lifetime. In collaboration with Cancer Research UK, the University of Southampton is playing a major part in the global fight to eradicate this condition.

The University has been at the forefront of cancer research for 40 years. Our long-established relationship with Cancer Research UK (CRUK) supports facilities such as Southampton’s CRUK Centre of Excellence and CRUK Experimental Cancer Medicine Centre. Leading the UK in cancer immunology research, the University has recently launched a fundraising campaign to open a world-leading Centre for Cancer Immunology at Southampton General Hospital in 2017.

Our aim is to foster high-quality cancer research, with an emphasis on translating mechanistic understanding in the laboratory into better diagnosis and personalised treatments for patients.

Younger women with breast cancer

Research led by Southampton’s Professor Diana Eccles focuses on younger patients, who have a significantly reduced chance of survival. Breast cancer is the most common type of cancer in the UK but, thanks to international research efforts, over 80 per cent of women are alive five years after diagnosis and at least two-thirds survive for 20 years or more. However, we know that women diagnosed under the age of 40 often have more aggressive cancers, with a significantly lower chance of survival, and some carry genetic factors predisposing them to the disease.

Diana and her team are examining inherited high-risk genes for breast cancer, such as BRCA1 and BRCA2, in this group, with a view to developing treatments for genetic breast cancer. “We are looking at the DNA from younger breast cancer patients to find out whether clues in the BRCA genes could help predict their response to treatment and the risk of cancer coming back,” says Diana. “There is some evidence that BRCA1 gene carriers may be more sensitive to certain types of chemotherapy. We want to empower women who carry this faulty gene to make informed decisions about their treatment options. Our research could also lead to targeted ways to treat young women with breast cancer and improve their chances of beating the disease.”

The POSH study

The Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH), led by Diana, ties in with a number of ongoing national and international collaborative studies. More than 3,000 women diagnosed with breast cancer under the age of 40 took part in the study. Only about five per cent of all breast cancers are diagnosed in women under 40 years of age, so over the eight years that patients joined the study, this makes up around a quarter of all women with breast cancer in this age group in the UK. Participants contributed a blood sample and tumour tissue for genetic research. The progress of study participants is followed annually.

“We are looking at the prognosis for breast cancer patients with BRCA1 or BRCA2 gene mutations, at differences in patterns of recurrence and at whether cancers in these patients have a distinct tumour phenotype or host tissue response,” says Diana. “We have already found that women diagnosed with breast cancer with a family history of the disease face a similar prognosis after treatment to other women with breast cancer. If the outlook for BRCA carrier patients is more optimistic than previously thought, preventive surgical options could be more confidently planned at the same time as breast cancer treatment.”

Southampton’s Experimental Cancer Medicine Centre, Clinical Trials Unit and the new Centre for Cancer Immunology, planned to open in 2017, are enabling us to accelerate the development of immunotherapy treatments and, ultimately, cures for cancers including breast cancer.

Diana Eccles – Professor of Cancer Genetics

Stopping cancer cell growth

Surgeon Ramsey Cutress is working alongside Diana in the study, and is also investigating combinations of treatments to stop HER2 positive breast cancer cells growing, including therapies that block internal signalling proteins as well as the action of growth factors. He explains, “We do not yet fully understand how some breast cancers evade drugs designed to block their growth. We must therefore develop more effective treatments that target breast cancer in multiple ways. The aim will be to improve treatments for breast cancer patients and reduce the risk of the disease returning after therapy has ended.”

Triple-negative breast cancer

Another important finding of the POSH study is the conclusion that young women with triple-negative breast cancer (TNBC) should be offered BRCA gene testing, whether or not they have a family history of cancer. Diagnosed most often in women before the menopause, TNBC is difficult to treat because the tumours are missing the oestrogen, progesterone and HER-2 receptors that can be targeted by the most common and most effective forms of therapy.

Working with the Mayo Clinic Cancer Centre in America, Diana and her team found that almost 15 per cent of TNBC patients had harmful mutations in the BRCA1 and BRCA2 genes. Even among very young women with TNBC with no family history of the disease, over 10 per cent of patients had a mutation. National guidelines for genetic testing have changed as a result of this and other studies. Breast cancers arising against a background of deficient DNA repair created by mutation in genes like the BRCA genes lead to highly mutated cancers, which may be more visible to the immune system. This could lead to new and better treatment options for patients with TNBC, particularly those with an underlying BRCA gene mutation.

The immune environment is clearly important in helping determine treatment outcomes in women with TNBC in the POSH study. Diana’s current work is unravelling the immune environment in young women with TNBC who are carrying the BRCA1 gene, compared to young women who have TNBC but no underlying gene mutation. This work is topical and timely, with heightened international interest in harnessing the immune system to improve cancer treatments. “Southampton’s Experimental Cancer Medicine Centre, Clinical Trials Unit and the new Centre for Cancer Immunology, planned to open in 2017, are enabling us to accelerate the development of immunotherapy treatments and, ultimately, cures for cancers including breast cancer,” says Diana.

PREDICTing cancer

Diana’s research has also contributed to the increased accuracy of PREDICT, a widely used online computer programme developed by Cambridge academics that predicts the prognosis of breast cancer. Although the Cambridge team studied thousands of UK women of all ages with breast cancer, inadequate data were available for younger women and the programme underestimated by 25 per cent the number of women under 40 who would die from the disease.

“POSH data give more accurate estimates for younger women and will help the group in Cambridge develop the software further,” says Diana. “Our research emphasises the growing understanding that breast cancer in young women can behave differently. Making predictions using information from mainly older women may not always be accurate enough for younger patients or for doctors trying to make important decisions about treatment.”

Genetic testing

Funding from the CRUK Biomarkers Research Panel is enabling Diana and her team to complete the genetic profiling for breast cancer susceptibility genes across the whole cohort of patients in the POSH study. “We anticipate that the primary analysis comparing outcomes in gene carriers versus non-carriers will be available in 2016,” she says.

Breast cancer research at Southampton is part of a global effort to understand, prevent and treat the many different forms of the disease. The POSH study is an invaluable resource for the international research community, providing data on significant numbers of younger women with the rarer, inherited and more difficult to treat cancers. “Our project ties in with a number of national and international collaborative studies,” Diana explains. “DNA samples collected from our recruits are enabling researchers worldwide to explore the factors that influence the pathobiology and prognosis of breast cancer, ultimately to work towards prevention and cure.”