Osteoporosis drug could benefit postmenopausal women with breast cancer

Drugs used to treat the bone condition osteoporosis could prevent 1000 breast cancer deaths a year, according to a large analysis of previous clinical trials.

The study published in The Lancet, showed that the drugs – called bisphosphonates – reduced the risk of breast cancer coming back, as well as significantly reducing the risk of death, in women diagnosed after their menopause with early-stage breast cancer.

Breast cancers most commonly spread to the bone, and treatment with bisphosphonates alters the bone tissue. This potentially makes the bone a more challenging environment for rogue cancer cells to survive in, reducing the risk of the cancer coming back.

To test this, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) set up by researchers at the Nuffield Department of Population Health,University of Oxford, alongside collaborators from Oxford University Hospitals NHS Trust and many other institutes, combined data from 18,766 women from 26 clinical trials, comparing women who took bisphosphonates for between two and five years, with those who had no bisphosphonates.

Postmenopausal women on bisphosphonates saw a 28 per cent reduction in the chances of their cancer coming back. Bisphosphonates also reduced the risk of dying from the disease during the first 10 years after diagnosis by 18 per cent.

Professor Robert Coleman, who led the study, said that the results show that giving postmenopausal women bisphosphonates after surgery could “prevent around a quarter of bone recurrences and one in six of all breast cancer deaths in the first decade of treatment”.

Cancer Research UK’s chief clinician, Professor Peter Johnson, said that while findings had the potential to save many lives, further in-depth research will be needed.

“This large analysis suggests that, if post-menopausal women with early breast cancer were given bisphosphonates after surgery, it could stop cancer spreading to their bones and save around 1,000 lives a year,” he said.

“Many women already get bisphosphonates to protect against bone disease, but before doctors give this drug to all post-menopausal women at high-risk of breast cancer, more thorough clinical trials are needed,” he added.

A second study by the EBCTCG, also published in The Lancet, looked at the effectiveness of different hormone therapies for breast cancer.

It’s results provide further support for recommendations by NICE that hormone therapies called aromatase inhibitors should be offered to women with early-stage oestrogen receptor (ER)-positive breast cancer, over an older hormone therapy called tamoxifen.

Researchers found that women with ER-positive breast cancer taking aromatase inhibitors for five years had a 40 per cent lower risk of dying within 10 years of starting treatment, compared to those who didn’t take hormone therapy.

This compared to a 30 per cent lower risk following five years of treatment with tamoxifen.

Aromatase inhibitors work by preventing the body from producing oestrogen, and are taken by postmenopausal women with ER-positive breast cancer. They have previously been shown to be more effective than tamoxifen in reducing the chances of cancer coming back, but the new study is the first to show a greater reduction in death rates.

The study looked at data from 31,920 women across nine international clinical trials, with each study including women who had been treated with aromatase inhibitors or tamoxifen at various times during the study.

Lead author Professor Mitch Dowsett, from The Royal Marsden and The Institute of Cancer Research, London, said the global research effort confirmed that aromatase treatment provided “significantly greater protection than that offered by tamoxifen”.

But he cautioned that aromatase therapy was not without its side-effects.

“Aromatase inhibitor treatment is not free of side-effects, and it’s important to ensure that women with significant side-effects are supported to try to continue to take treatment and fully benefit from it,” he said.

The power of such long-term analyses was welcomed by Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, who said they were crucial for bringing the best treatments to patients.

“It tends to be the discovery of new treatments that grabs the headlines, but it is just as important to maximise the benefit patients get from existing treatments, through major, practice-changing studies like this,” he said.

Both studies were funded by Cancer Research UK and the Medical Research Council.

 

References

  • Early Breast Cancer Trialists’ Collaborative Group: Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet (2015) DOI:10.1016/ S0140-6736(15)60908-4
  • Early Breast Cancer Trialists’ Collaborative Group: Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet (2015) DOI:10.1016/S0140-6736(15)61074-1

Source: Cancer Research UK in collaboration with the Press Association 

 

Genetic expression ‘predicts lung cancer survival’

A study led by Oxford University researchers and colleagues at the National Cancer Institute, Milan, Italy has shed light on a key puzzle thrown up in some lung cancer screening programmes.

Italian researchers have screened more than 5000 heavy smokers over the last fifteen years, using CT scans to detect lung cancer early. While the proactive CT screening of smokers has been good at discovering developing cancer tumours, finding them more frequently than expected, the programmes have not had a clear effect on reducing deaths from cancer. The research team decided to look at whether the way different genes were expressed in various tumours could account for why some people survived and others did not, despite the early detection by the screening program.

Lead researcher Dr Jiangting Hu said: ‘If you are doing well at finding tumours, you would expect to be reducing deaths by treating people earlier. But there was no clear link between this early detection and survival rates. We hypothesised that the screening programmes were mostly finding indolent – slow-growing – tumours. These indolent tumours were removed, but there were also aggressive, fast-growing, tumours developing. These fast-growing tumours do get found by screening but later as they develop and, even if detected very early, already have a very aggressive phenotype.

The researchers looked at the gene expression pattern of tumours that had been detected by CT scans and compared the differences between the pattern detected at baseline and the pattern detected later on. Different expression of some genes can lead similar tumours to behave in different ways. The genetic expression in the tumours was compared with other information about the cancer cases.

The team found 239 genes whose expression was related to cancer survival rates.

Professor of Tumour Pathology and CRUK Oxford Centre Member Francesco Pezzella said:The striking thing was that the 239-gene signature divided the patients into two groups that clearly predicted disease-free survival and also divided the indolent tumours detected at baseline from the tumours which were found later on during the screening program, regardless of tumour stage or size, and any histopathology findings from studying the tissue. We also found that the genetic expression in healthy cells differed between those two groups of people. Furthermore the same signature could divide indolent from very aggressive tumours in patients as part of normal clinical practice.

‘The results confirmed that there is a difference between indolent and aggressive tumours, which could be used to identify those with more dangerous tumours for personalised care. They also show that we could profile healthy tissue to identify high and low risk groups. A final remarkable finding is that the team led by Ugo Pastorino and Gabriella Sozzi in italy has discovered that the same genetic differences can be seen with a blood test in the same patients.

‘The next step will be finding shorter gene signatures, enabling us to develop more personalised diagnosis to facilitate better targeted cancer treatment.’

The paper, Gene Signatures Stratify Computed Tomography Screening Detected Lung Cancer in High-risk Populations, is published in EBioMedicine.