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01 Feb 2024

Biomarkers discovered for difficult-to-diagnose breast tumour

Researchers are a step closer to improved diagnosis for rare breast tumours called phyllodes tumours, thanks to new findings from the Garvan Institute of Medical Research.

A phyllodes tumour's characteristic leaf-like cellular structure is not enough to identify it as malignant or benign, as in this borderline case.
A phyllodes tumour's characteristic leaf-like cellular structure is not enough to identify it as malignant or benign, as in this borderline case.

The epigenetic ‘signature’ of a rare, hard-to-diagnose breast tumour has been found by scientists at the Garvan Institute of Medical Research. The discovery could lead to improved treatment guidelines and better outcomes for patients with this rare disease.

Accounting for less than 1% of breast tumours, phyllodes tumours can be difficult to diagnose due to their similarity under the microscope to other types of breast tumours. Most phyllodes tumours are benign, but 10% are malignant. Accurate diagnosis is crucial for effective treatment, as misdiagnosis results in inappropriate or delayed treatment.

The standard diagnosis of tumours comes from pathology analysis of cell patterns but researchers at Garvan have found that new epigenetic-based DNA markers may give additional information for diagnosis.

Epigenetic changes affect whether gene activity is turned up or down without altering the DNA sequence, and can be influenced by environmental factors. A common epigenetic mechanism is DNA methylation, where molecules called methyl groups attach to parts of DNA, which can change gene expression.

“The current way of diagnosing phyllodes tumours is to analyse their cellular features under a microscope. But this technique means they can be misdiagnosed as cellular fibroadenomas, sarcomas or metaplastic breast cancer, tumour types that may look the same but have very different growth rates, prognoses and treatment pathways. Our epigenetic approach, looking at DNA methylation patterns, provides a new layer of information to add to traditional pathology,” says Dr Ruth Pidsley, co-senior author of the study and Leader of the DNA Methylation Biomarkers Group at Garvan.

The findings were published in the Journal of Pathology.

Associate Professor Clare Stirzaker, Dr Braydon Meyer, Dr Ruth Pidsley, Professor Sandra O'Toole and Professor Susan Clark

Diagnostics informed by epigenetics

Analysing samples from 33 patients, the researchers found that phyllodes tumours exhibit a unique DNA methylation pattern, allowing them to be distinguished from other cancers.

“In addition to finding this new epigenetic signature, we identified an additional methylation pattern that could be used to differentiate malignant phyllodes tumours from benign cases. We also developed an algorithm that reclassified originally misdiagnosed samples,” says Dr Braydon Meyer, Research Officer in the Cancer Epigenetics Lab.

“Altered DNA methylation patterns have been instrumental in diagnosing other cancer types, showing the broader potential of epigenetic biomarkers in precision cancer diagnosis and personalised treatment,” says Associate Professor Clare Stirzaker, Leader of the Cancer Epigenetic Biomarker Group and co-first author on the paper. 

The new understanding could lead to improved diagnosis and outcomes. “Getting the diagnosis right means patients can receive the most appropriate treatment, improving chances of survival for those with aggressive tumours and avoiding unnecessary treatments for those with benign ones,” says Professor Sandra O’Toole, co-senior author and a senior pathologist at Garvan.

“Disruption to epigenetic processes, such as DNA methylation patterns, is a recognised hallmark of cancer and can vary significantly between cancer types, allowing a unique cancer forensic signature,” says Professor Susan Clark, co-senior author and Head of the Cancer Epigenetics Lab at Garvan. “Harnessing the power of cutting-edge epigenetic technologies, like Digital Droplet PCR, our next step will be devising a sensitive epigenetic-based PCR test to detect phyllodes tumours that could be routinely used in pathology laboratories.”


This work was supported by the National Breast Cancer Foundation (NBCF IIRS 22-060, NBCF IIRS 18-137, NBCF IIRS 19-084), the Sydney Breast Cancer Foundation, the National Health and Medical Research Council (#2010156, #1063559, #1128916) and Tour de Cure.

Associate Professor Clare Stirzaker is a Conjoint Associate Professor, Dr Braydon Meyer is a Conjoint Lecturer, Dr Ruth Pidsley is a Conjoint Lecturer and Professor Susan Clark is a Conjoint Professor at St Vincent's Clinical School, Faculty of Medicine and Health, UNSW Sydney. Professor Sandra O’Toole is a Clinical Professor at the School of Medical Sciences, Faculty of Medicine and Health, the University of Sydney.