LC–MS/MS metabolite panel shows potential for breast cancer assessment

Targeted LC–MS/MS analysis of methionine-cycle metabolites could support luminal breast cancer assessment, staging and prediction of response to chemotherapy agent palbociclib

A liquid chromatography–tandem mass spectrometry study has identified changes in methionine-cycle metabolites that could help researchers to assess luminal breast cancer, determine disease stage and predict response to the cancer medicine palbociclib.

Researchers in China from the Nanjing Medical University, Nanjing, Jiangsu, China, analysed plasma samples from 146 patients with luminal breast cancer and 36 healthy controls. Luminal tumours account for most breast cancer cases and commonly express hormone receptors, which allows clinicians to treat them with endocrine therapies.

Although these treatments can be effective, some tumours eventually develop resistance and progress or return. The researchers therefore examined whether changes in the methionine cycle could provide measurable indicators of disease development and treatment response.

The methionine cycle supports several fundamental cellular processes, including methylation, antioxidant defence and the production of molecules required for cell growth. Its principal metabolites include methionine, S-adenosylmethionine, S-adenosylhomocysteine and homocysteine.

The team used liquid chromatography–tandem mass spectrometry to quantify these compounds. Compared with the healthy participants, patients with luminal breast cancer had lower plasma concentrations of all four metabolites.

When the researchers combined the measurements, the resulting panel distinguished patients with cancer from controls with an area under the receiver operating characteristic curve of approximately 0.81. This measure indicates how effectively a model separates two groups, with a value of one representing perfect discrimination.

Patients with advanced disease had further reductions in methionine, S-adenosylmethionine and S-adenosylhomocysteine. The ratio between S-adenosylmethionine and S-adenosylhomocysteine was also lower than that observed among patients with early-stage disease.

A combined metabolic signature distinguished early-stage from advanced cancer with an area under the curve of approximately 0.92. Lower concentrations of several metabolites also occurred among patients who responded poorly to palbociclib, a cyclin-dependent kinase 4 and 6 inhibitor used to treat some hormone-receptor-positive breast cancers.

The researchers incorporated five measurements into a predictive nomogram. The model achieved accuracy of more than 90% within the training cohort and approximately 80% when it was applied to a separate validation group.

These results suggest that methionine-cycle measurements could provide biochemical information that complements imaging, histopathology and established molecular tests. Liquid chromatography–tandem mass spectrometry also offers the selectivity required to measure closely related metabolites within complex biological samples.

The findings remain preliminary. The study involved a relatively small number of participants from a limited clinical population and the reported models will require prospective validation across larger, independent and more diverse groups. Researchers must also establish whether factors such as diet, medicines, liver function or other illnesses affect the measurements.

The work does not show that the metabolite panel can replace present diagnostic or monitoring procedures. Instead, it provides evidence that disrupted methionine metabolism could carry clinically useful information.

The study illustrates the growing role of targeted liquid chromatography–tandem mass spectrometry in translational cancer research and the search for minimally invasive markers of disease progression and treatment resistance.

For further reading please visit: 10.3892/ol.2026.15795