Molecular patterns key to predicting breast cancer progression

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The genetic and molecular make-up of individual breast tumours holds clues to how a woman’s disease could progress, including the likelihood of it coming back after treatment, and in what time frame, according to a Cancer Research UK-funded study.

In the first study of its kind, scientists at the Cancer Research UK Cambridge Institute at the University of Cambridge, in collaboration with Professor Christina Curtis at Stanford University, examined the patterns of genetic changes within tumours from nearly 2000 women with breast cancer and followed their progress over 20 years – including whether their cancer returned. They then used this information to create a statistical tool that can better predict if, and when, a woman’s breast cancer could come back.

Although not available to patients yet, this means that in the future, treatments and follow-up can be tailored, improving women’s chances of survival.

Previous results from this group of researchers had already revealed that breast cancer isn’t just one disease, but instead could be classified into one of eleven different molecular subgroups.

The latest findings, published in Nature, highlight how these molecular subtypes have distinct clinical ‘trajectories’, which can’t be predicted by looking at commonly used characteristics (such as size, stage, oestrogen receptor (ER), or Her2 status) alone.

These clinical trajectories vary considerably, even between tumours that seem similar. For example, the team found, among women with a form of the disease called triple-negative breast cancer, that there was a distinct subgroup whose outlook is initially poor, but for whom the disease is unlikely to come back in those who survived five years.

They also identified subgroups of women with oestrogen receptor-positive (ER+) tumours, who were at a higher risk of their cancer coming back up to 20 years after they were first diagnosed. Around 12,300 women in the UK could belong to one of these late relapse subgroups and therefore might benefit from longer courses of treatments such as tamoxifen, or more frequent check-ups.

The model also revealed how molecular subgroups could behave very differently if a patient’s cancer returns. They commonly spread to different parts of the body and some are more aggressive than others, affecting how much time women survive for following a relapse.

Professor Carlos Caldas, lead researcher at the Cancer Research UK Cambridge Institute, said: “Treatments for breast cancer have improved dramatically in recent years, but unfortunately for some women, their breast cancer returns and spreads, becoming incurable. For some, this can be many years later – but it’s been impossible to accurately predict who is at risk of recurrence and who is all clear.

“In this study, we’ve delved deeper into breast cancer molecular subtypes so we can more accurately identify who might be at risk of relapsing and uncover new ways of treating them.”

Dr Oscar Rueda, first author of the paper and senior research associate at the Cancer Research UK Cambridge Institute, said: “We hope that our research tool can be turned into a test doctors can easily use to guide treatment recommendations.”

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “We’re still a way off being able to offer this type of detailed molecular testing to all women and we need more research to understand how we can tailor treatments to a patient’s individual tumour biology. But this is incredibly encouraging progress.”

In addition to developing an affordable test for future use in hospitals, Caldas’ team are also investigating personalised treatment options for different breast cancer subtypes. The next steps will be to recruit patients onto different clinical trials depending on the molecular make-up of their tumour.