Breast cancer image

Research could lead to more effective treatment.

As the current work shows, future sequence-guided clinical trials will require collaborations between major cancer centres, such as Cambridge and Vancouver, which are able to recruit the required numbers of patients from an increasingly better defined disease. That is now one of the priorities of the Breast Cancer Program in Cambridge.

Professor Carlos Caldas, study co-lead, senior group leader at Cancer Research UK’s Cambridge Research Institute and Professor of Cancer Medicine at the Department of Oncology, University of Cambridge

University of Cambridge scientists, led by Professor Carlos Caldas, based at the Cancer Research UK Cambridge Research Institute at the Cambridge Biomedical Campus, working with BC Cancer Agency scientists in Vancouver (led by Professor Sam Aparicio) have jointly decoded the genetic make-up of triple negative breast cancer, which could lead to more effective treatment.

The study, published online last week in the international journal Nature, reveals that this form of cancer is not one distinct single entity, but an extremely complex and evolved tumour with an unprecedented range of mutations.

Operating with the complexity of a mini ecosystem, triple negative breast cancers’ evolution before diagnosis may explain its ability to evade current therapies, earning it the distinction as the deadliest form of breast cancer.

The research team, including scientists from BC Cancer Agency, University of British Columbia, Cross Cancer Institute of Alberta and Cancer Research UK/University of Cambridge, unmasked this evolving cellular “ecosystem” and can now estimate how the genetic mutations accumulated prior to diagnosis.

Named for what it isn’t, triple negative breast cancer is currently defined by three missing cancer-causing proteins (the oestrogen receptor, progesterone receptor and ERBB2 receptor), compared to other breast cancer subtypes. Triple negative breast cancer is currently treated as if it’s a single disease, yet it’s clear from this study that patients’ tumours vary drastically across a spectrum of cellular mutations involved in the cancer’s development. Currently, triple negative breast cancer accounts for 16 per cent of all breast cancer diagnoses and approximately 25 per cent of breast cancer deaths.

In approximately 20 per cent of cases studied, the tumours revealed groupings of genetic mutations (so-called 'actionable mutations') that already have potential clinical treatment options in the pipeline. This leads researchers and clinicians toward a future where patients’ tumours could be sequenced as a means to better direct targeted therapies.

Pinpointing the exact cellular mutations involved is an important first step in understanding why patients respond differently to treatment. More effective treatments come from being able to identify and target the genetic factors that play a role in the cancer’s growth.

This discovery implies that researchers and clinicians won’t fully understand triple negative breast cancers until they are studied through routine sequencing. In fact, the study suggests there is value in looking at patients’ responses to treatment based on their tumours’ genetic features.

Scientists and clinicians in Cambridge, based at the Cambridge Breast Cancer Research Unit, are now working toward a future of personalized breast cancer medicine, supported by the Cambridge Experimental Cancer Medicine Centre and with infrastructure support from the National Institute of Health Research Comprehensive Biomedical Research Centre at Addenbrooke's Hospital.

Professor Carlos Caldas, study co-lead, senior group leader at Cancer Research UK’s Cambridge Research Institute and Professor of Cancer Medicine at the Department of Oncology, University of Cambridge said: “As the current work shows, future sequence-guided clinical trials will require collaborations between major cancer centres, such as Cambridge and Vancouver, which are able to recruit the required numbers of patients from an increasingly better defined disease. That is now one of the priorities of the Breast Cancer Program in Cambridge.”

The Cancer Research UK Cambridge Institute is a major research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. The Institute is a unique partnership between the University of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge University, Cancer Research UK, The Atlantic Philanthropies and a range of other donors.  For more information visit www.cruk.cam.ac.uk.


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