Chromatography Links Metabolites to Breast Cancer

Chinese researchers used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to look at levels of a group of substances known as the methionine cycle and compared blood samples from people with luminal breast cancer) to samples from those who were not suffering from the disease. They looked at how these substance levels differed between the two groups as well as tracking how they changed as the cancer progressed from early to more advanced stages. The researchers believe that their study took steps in revealing how luminal breast cancer affects the body's chemistry and offers a new way to more accurately evaluate treatment effectiveness and improve strategies for dealing with drug resistance. A paper based on their work was published in the journal Oncology Letters.¹

What is Luminal Breast Cancer and Why Is It Important to Closely Monitor How It Progresses Over Time?

Breast cancer is the most common cancer diagnosed in women around the world, with more than 2.3 million new cases every year.² The disease typically develops from a mix of different factors working together—things like genetics, hormone levels, lifestyle habits, and environmental exposures—which can cause normal breast cells to turn cancerous.³

Out of all the different types of breast cancer, about 70% fall into what's called the "luminal subtype," which is further split into two groups: luminal A and luminal B. These types are identified by certain markers on the cancer cells, like hormone receptors and the protein human epidermal growth factor receptor (HER).³ The luminal subtype relies on hormones to grow, so when it's caught early, patients usually respond well to hormone-blocking treatments. However, about 20% of these patients eventually see their cancer come back or spread to other parts of the body because the cancer stops responding to hormone therapy. When this happens, the disease advances to a more serious stage and becomes harder to treat successfully.^4-6 “Therefore,” write the authors of the paper,¹ “close attention to the dynamic progression of luminal breast cancer is highly important.”

Can Methionine Cycle Metabolites Diagnose Luminal Breast Cancer, Distinguish Disease Stage, and Predict Resistance to Palbociclib?

This study included 146 patients with luminal breast cancer and 36 healthy people for comparison, all recruited from Jiangsu Cancer Hospital in Nanjing, China. The researchers found that cancer patients had lower levels of four substances (methionine, S‑adenosylmethionine (SAM), S‑adenosylhomocysteine (SAH) and homocysteine) compared to healthy people, and combining these measurements could identify cancer patients fairly accurately (correctly distinguishing the groups about 81% of the time). Patients with more advanced cancer had even lower levels of methionine, SAM, and SAH, along with a lower SAM-to-SAH ratio, compared to patients with early-stage cancer, and combining these measurements was very accurate at telling early from late-stage disease (an accuracy rate of approximately 92%).¹

The researchers also found that patients who did not respond well to the cancer treatment drug palbociclib had lower levels of SAH, SAM, and homocysteine, and combining these levels could identify drug-resistant patients with about 92% accuracy. Finally, they used these findings to build a prediction tool (called a nomogram) using five key measurements, which worked well both in the original patient group (over 90% accurate) and when tested on a separate group of patients (80% accurate).¹

“The present results,” write the authors of the paper,¹ “suggest that methionine cycle-related metabolites are promising potential biomarkers for the diagnosis and progression assessment of luminal breast cancer. Furthermore, the constructed nomogram prediction model provides a new strategy for timely clinical treatment and intervention.”

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References

1. Wu, W.; Tu, Y.; Yao, H. et al. LC-MS/MS-Based Clinical Value Exploration of the Methionine Cycle in Luminal Breast Cancer. Oncol Lett. 2026, 32 (4), 440. DOI: 10.3892/ol.2026.15795
2. Bray, F.; Laversanne, M.; Sung, H. et al. Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2024, 74 (3), 229-263. DOI: 10.3322/caac.21834
3. Abdulkareem, I. H. Aetio-Pathogenesis of Breast Cancer. Niger Med J. 2013, 54 (6), 371-375. DOI: 10.4103/0300-1652.126284
4. Hany, D.; Vafeiadou, V.; Picard, D. CRISPR-Cas9 Screen Reveals a Role of Purine Synthesis for Estrogen Receptor α Activity and Tamoxifen Resistance of Breast Cancer Cells. Sci Adv. 2023, 9 (19), eadd3685. DOI: 10.1126/sciadv.add3685
5. Giaquinto, A. N.; Sung, H.; Newman, L. A. et al. Breast Cancer Statistics 2024. CA Cancer J Clin. 2024, 74 (6), 477-495. DOI: 10.3322/caac.21863
6. Makhlouf, S.; Wahab, N.; Toss, M. et al. Evaluation of Tumour Infiltrating Lymphocytes in Luminal Breast Cancer Using Artificial Intelligence. Br J Cancer 2023, 129 (11), 1747-1758. DOI: 10.1038/s41416-023-02451-3