Mitochondrial Genes Can Help Predict Breast Cancer Treatment Outcome, Study Shows

Researchers have found more than 60 mitochondrial biomarkers that can be used to predict tumor recurrence in breast cancer patients who were previously treated with tamoxifen, according to a new study.

This finding not only opens new possibilities to identify high-risk patients for cancer recurrence, allowing a more precise and personalized therapy, but it also recognizes mitochondrial genes as potential therapeutic targets for cancer prevention.

The study, titled “Mitochondrial markers predict recurrence, metastasis and tamoxifen-resistance in breast cancer patients: Early detection of treatment failure with companion diagnostics,” was published in the journal Oncotarget.

Drug resistance is the main obstacle for effective anti-cancer therapies, and is a major cause for treatment failure and cancer recurrence. That means finding new ways to promote early detection of disease recurrence, and to predict how cancer cells will respond to treatment, is essential for prompt and effective patient care.

“Early detection of cancer recurrence is everything; if we have information about a patient’s prognosis we can act much more effectively,” Dr Michael P. Lisanti, professor of translational medicine at the University of Salford and senior author of the study, said in a news release.

“You never know if cancer will return or how to prepare for that, so knowing who will and who won’t respond well to treatment offers reassurance to doctors, patients and families, and allows a degree of closer monitoring,” Dr. Lisanti said.

The research team analyzed the expression of more than 400 mitochondrial genes in 145 patients with breast cancer who had been treated with tamoxifen and followed for at least 15 years. They found more than 60 new, individual mitochondrial biomarkers that could predict treatment failure and tumor recurrence in this population.

Among these genes, they found that high levels of HSPD1 and VDAC2 mitochondrial genes represented a 3.6 and 4.2 times higher risk of treatment failure and cancer recurrence, respectively.

These mitochondrial biomarkers proved more accurate in predicting patients’ response to treatment than other currently used biomarkers, including Ki67 or PCNA, which only represented 2.5 and 1.8 increased risk of treatment failure, respectively.

“In practical terms, a person in remission could be predicted to be 80% likely to fail treatment,” said Dr Federica Sotgia, investigator at the University’s biomedical research centre and first author of the study. “If doctors can predict that a treatment will likely fail, it gives them more positive options; either they can monitor the patient more closely or offer an alternative course of treatment.”

In addition, the team observed that when combining the expression levels of a set of specific mitochondrial genes, it was possible to predict a patient outcome with even greater accuracy. They showed that patients with high levels of both HSPD1 and VDAC2 had a 5.2 times increased risk of poor treatment outcome and occurrence of distant metastasis (growth of cancer cells distant from the primary cancer site).

The researchers further validated these finding is a cohort of 3,180 patients with breast cancer, confirming the potential of mitochondrial genes to predict tumor recurrence, distant metastasis, and treatment failure.

“We identified individual mitochondrial biomarkers and 2 compact mitochondrial gene signatures that can be used to predict tamoxifen-resistance and tumor recurrence, at their initial diagnosis, in patients with advanced breast cancer,” the researchers wrote in the report. “In the long-term, these mitochondrial biomarkers could provide a new companion diagnostics platform to help clinicians to accurately predict the response to hormonal therapy.”