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Techniques & Tools Mass Spectrometry, Proteomics

Breast Cancer Protein Patrol

Genetic predisposition can increase a person’s chance of developing breast cancer by up to 72 percent. Although screening programs are widely available, “interval cancers” can occur between regular screening sessions – and the clinical need for early detection remains fundamental. With that in mind, researchers from the Netherlands developed a quick, minimally invasive proteomics-based diagnostic test for those susceptible to breast cancer (1).

The researchers drew on the findings of the prospective, multicenter TESTBREAST study, founded by Leiden University Medical Centre’s Wilma Mesker and Rob Tollenaar in 2011 to analyze blood-based protein biomarkers in women with a high risk of developing breast cancer. The ongoing study involves acquiring serum samples from its 1,174 female participants every half a year until diagnosis. Recently, the first analyses of a subset of TESTBREAST participants were conducted on 30 longitudinal blood samples from six women – three who developed a breast malignancy and three controls (2). The researchers analyzed prediagnostic changes in protein levels using targeted mass spectrometry-based proteomics, a technique chosen for its ability to identify and quantitate a large number of serum proteins.

The analysis revealed unique patterns of protein clustering in individual patients, indicating a greater inter-patient than intra-patient variability in protein levels of the longitudinally obtained samples. Most importantly, six proteins showed changes up to two years before diagnosis, suggesting their utility as early indicators of breast cancer onset. “Women with hereditary breast cancer attending outpatient clinics can now have the test performed more often, and have early detection of aberrant signals of proteins in the blood,” says Mesker. “This offers opportunities for clinical decision-making – including preventive prophylactic mastectomy.”

In the future, the authors hope to validate their findings in the complete TESTBREAST cohort and then in a larger national or international setting. Mesker explains, “The long-term aim is to have the test available in point-of-care settings to complement MRI screenings and to achieve early detection of breast cancer in patients with increased genetic risk.”

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  1. SC Hagenaars et al., Eur J Cancer, 175, S1 (2022). DOI: 10.1016/S0959-8049(22)01351-X.
  2. SC Hagenaars et al., Int J Mol Sci, 23, 12399 (2022). DOI: 10.3390/ijms232012399.
About the Author
Georgia Hulme

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