Click for a full size image
A Better Way to Breast Cancer Care – How Precision Medicine Helps Clinicians Identify the Best Treatment
This article was originally published in the Northwestern University Feinberg School of Medicine News Center. It has been edited for the Breakthroughs in Care audience.
About 75 percent of breast cancers are estrogen receptor (ER)-positive, which means the cancer cells contain proteins that receive signals from the hormone estrogen to promote cell growth. Identifying mutations in the ER gene can help clinicians choose effective therapies for patients with metastatic breast cancer, according to recent research co-authored by Northwestern Medicine scientist Massimo Cristofanilli, MD.
Aromatase inhibitors, which block the enzyme that produces estrogen, are the standard of care for ER-positive breast cancer, but patients with metastatic cancer often become resistant to those drugs.
In recent research, Cristofanilli and colleagues focused on patients with advanced ER-positive breast cancer that had progressed despite aromatase inhibitor therapy. The scientists wanted to know if patients in this group who had mutations in the ER gene (ESR1) would be more or less sensitive to additional hormone therapies.
“We evaluated whether ER mutations detected in plasma of patients enrolled in two clinical trials could indicate the most effective treatment. Mutations were studied in circulating tumor DNA of blood specimens collected before patients started treatment,” explained Cristofanilli, a professor of Medicine in the Division of Hematology/Oncology and associate director for Precision Medicine and Translational Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The scientists looked at two studies to inform their findings. The first study compared therapeutic strategies involving two different hormone treatments, the drugs fulvestrant and exemestane. By analyzing DNA, Cristofanilli and colleagues determined that about 40 percent of patients enrolled in this study had ESR1 mutations. The scientists discovered that patients with the mutations had better rates of survival after taking the drug fulvestrant compared to the drug exemestane, while patients without the mutations had similar results on both regimens.
A second study compared fulvestrant plus a placebo to fulvestrant plus the drug palbociclib. The latter strategy improved survival for patients with the mutation and patients without it.
“The evidence shows that when there’s an ER mutation in a patient with metastatic breast cancer, it’s more appropriate to use fulvestrant than aromatase inhibitors,” Cristofanilli said.
The findings suggest that clinicians should use molecular diagnostic tests to find out if a patient has ER mutations before making a decision about the best hormone therapy to pursue.
“Our study strongly suggests that checking for these mutations should be a standard of care,” Cristofanilli said. “It’s very important to carefully select the patients who would benefit most from a targeted therapy. This kind of precision medicine approach increases a patient’s chance of responding to treatment.”
In future research, Cristofanilli and colleagues will analyze the implications of other genetic mutations in patients with advanced breast cancer. They are also designing studies that incorporate upfront screening of mutations in genes like ESR1 when testing new targeted therapies.
source: Northwestern University – Northwestern Medicine