Enhancing outcomes after surgery of breast cancer patients with miR-145

According to research results published online ahead of print in the Journal of the American College of Surgeons (JACS), microRNA (miRNA) can be used as a biomarker to identify which individuals are most likely to experience breast cancer recurrence and mortality.

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Breast cancer is the most frequent cancer diagnosed in women, and while long-term outcomes have improved, 20% to 30% of patients will experience recurrence. It has been difficult to pinpoint which patients are most likely to experience a recurrence.

To ascertain whether miRNAs—small, non-coding molecules that regulate the genetic expression and impact cancer development—can predict which breast cancer patients are more likely to experience a recurrence of the disease and pass away from it, a research team in Galway, Republic of Ireland, set out to do just that.

The researchers found that patients who express miR-145, a specific type of miRNA, more frequently are less likely to experience a breast cancer recurrence. Lead author Matthew G. Davey, MRCSI, PhD, Discipline of Surgery, University of Galway, Republic of Ireland, described how miR-145 prevented the onset and spread of cancer.

We showed that increased expression of this biomarker, which was measured in patients’ blood samples during chemotherapy, actually predicted their long-term oncological outcome. We can predict those who are likely to suffer recurrence and those who will be free of recurrence.”

Matthew G. Davey, MRCSI, PhD, Discipline of Surgery, University of Galway

Dr Davey added, “We showed that increased expression of this biomarker, which was measured in patients’ blood samples during chemotherapy, actually predicted their long-term oncological outcome. We can predict those who are likely to suffer recurrence and those who will be free of recurrence.”

The authors believe that miR-145 could help identify patients who could benefit from closer breast cancer surveillance and a tailored treatment strategy in the postoperative phase of treatment. Likewise, it could also identify patients who are at lower risk of recurrence and may not need systemic treatments, which often can have harmful side effects.

This biomarker will help us give the right treatment to the right patients.”

Michael J. Kerin, MCh, FRCSI, FRCS.Ed., FRCS Gen., Study Co-Author and Chair of Surgery, University of Galway

Study details

124 patients were enrolled in this prospective, multicenter trial who received standard-of-care neoadjuvant chemotherapy for localized advanced breast cancer at eight different treatment facilities around Ireland. Depending on the medical staff’s assessment, the patient received a variety of chemotherapy treatments.

Over a three-year period (May 2011–April 2014), blood samples were taken from the patients twice: once at the time of diagnosis and once midway through chemotherapy. Expression levels of miRNA were assessed at each time point to determine their functions in determining whether the patient will be free of recurrence or disease along with their overall survival.

Key findings

The research discovered a correlation between elevated miR-145 expression and better results at approximately nine years of follow-up.

• Increased miR-145 independently predicted improved recurrence-free survival (HR: 0.00, 95% CI: 0.00–0.99, P = 0.050) and trended towards improved disease-free survival (HR: 0.00, 95% CI: 0.00–1.42, P = 0.067) when statistical analyses were performed
• Overall survival was not predicted by elevated miR-145 expression levels

Future research opportunities

Although the study was not powered or designed to ascertain how well miR-145 predicted outcomes for any specific subtype of breast cancer, the researchers examined individuals with any of the five subtypes of cancer. To aid with the solution, they intend to conduct additional clinical trials.

According to Professor Kerin, studies are also being conducted to see whether breast cancer patients’ miRNA expression can be elevated.

“One trial is testing miRNA replacement therapies in mice, but the research is in its early stages and it is unclear if the therapy could be transferred to humans,” added professor Kerin.

According to Dr Davey, his team intends to carry out a trial that is similar to the one they recently published in JACS and that focuses on a particular subtype of breast cancer (HER2-positive patients).