A New Clue Offers Insight on Why Some Breast Cancer Patients Relapse


A study carried out by Lucy Yates, MD, a clinical research oncologist, and her team at the Wellcome Trust Sanger Institute in Cambridge, U.K, on why some breast cancer patients relapse after treatment has unearthed a new clue to its occurrence. Her team has conducted one of the most extensive studies to date to find the reasoning behind this phenomenon.

Even though most breast cancer cases show no further relapse after treatment, 20 percent of patients report the reoccurrence of breast cancer. The study, which was conducted to understand the genetic sequencing of breast cancer tissue, revealed that the patients who came in for a second time for treatment for breast cancer exhibited a different genetic profile than the rest.

The study followed up on the clue, stating that the genetic drivers of relapsed cancers are targetable with drugs. Dr. Lucy Yates commented, “We demonstrate that there are clear differences within the driver landscapes of relapsed cancers. This probably reflects a combination of predisposition to relapse and of differences in the mutations acquired during the relapse and metastasis phase.”

The new clue into why some patients of breast cancer relapse offers renewed hope for breast cancer patients, as it can help doctors identify who is at risk of relapsing when they first diagnose the patient with it.

The team of researchers plans to present their study’s findings at the European Cancer Congress (ECC) 2015. The study, which was a rigorous effort by the group of researchers to find the underlying cause for relapse, took 836 tissue samples from women diagnosed with breast cancer and 161 tissue samples from patients, who had relapsed, to compare the genetic makeup of breast cancer.

Additionally, they examined 365 genes involved in cancer-linked pathways. The researchers carried out de novo driver mutation discovery and explained each individual mutation that breast-cancer-2.pngcould likely be connected to relapse by comparing it with established data. They performed the comparison using the Benjamini–Hochberg’s multiple testing correction and Fisher’s exact test. The team uncovered 11 genes, finding them to be enriched in relapsed cancer patients. Next, the team used multiple samples from 66 patients and 21 samples from patients with primary tumor to perform the multi-sample test, which allowed them to gain an insight into the evolution of the mutations.

In a statement, Dr. Yates said, “We have found that some of the genetic mutations that drive breast cancers that relapse are relatively uncommon amongst cancers that do not relapse at the point of primary diagnosis.”

Fabrice André, MD, PhD from the Gustave Roussy Institute, wanted to know if the researchers could identify every enriched gene they found in the relapsed samples as recurrent markers. He also noted that in another study using 183 samples, researchers only found one enriched gene, but Dr. Yates’ team found 11.

Another question Dr. Andre had for Dr. Yates and her team was if they could prove whether any of the late mutations were clinically relevant, and whether they could offer an explanation on why some cancers are resistant to therapy.

According to Dr. Yates, they still need to perform genomic analysis of relapsed, primary, and matched tissues. Another researcher, Anne-Lise Borresen-Dale, MD, from the Institute for Cancer Research, stated the need for researchers to perform biopsies repeatedly.

Dr. Yates concluded her study saying, “We believe that the differences we have seen reflect genetic differences that can predispose a cancer to return, combined with mutations acquired throughout the period from first diagnosis to the subsequent relapse.”


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