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Inova Schar Cancer is one of the top recruiting locations for the EMBER-4 clinical trial, a global study to evaluate a new treatment for ER+ HER2- breast cancer survivors

EMBER-4 is a Phase 3 clinical trial comparing a new drug therapy, imlunestrant, to the standard drug therapy to treat women with ER+ HER2- breast cancer. The trial is being conducted at multiple locations around the world, with Inova Schar Cancer named as one of the top recruiting centers in the United States.

“This pill is the first therapy in 30 years that could potentially replace endocrine therapy,” said study Kathleen Harnden, MD, Medical Director of Breast Oncology at Inova Schar Cancer and the principal investigator for the EMBER-4 clinical trial at Inova Schar Cancer. “This study is a bit of a unicorn. It is extremely patient centered and provides a rare opportunity to evaluate a treatment that may be better, with a higher cure rate, a lower risk of spread of breast cancer and fewer side effects.”

What is ER+ HER2- breast cancer?

Breast cancer is the most common cancer diagnosed in women (other than skin cancer). Breast cancer comes in many forms, which are often differentiated at the molecular level. The EMBER-4 clinical trial focuses on two molecular factors: cancer that is positive for estrogen hormone receptors (ER+) and negative for the human epidermal growth factor receptor 2 (HER2-).

ER+ cells are fueled by abnormal estrogen signaling that can propagate cancer growth. As such, this type of cancer is typically treated using antiestrogen (endocrine) hormone therapy to block cancer growth.

HER2 is a protein that sits on the surface of breast cells and controls the growth and repair of healthy breast tissue. Patients with HER2- breast cancer have very little to no HER2 proteins on the surface of the cell, which causes the cells to grow slowly.

How is ER+ HER2- breast cancer treated?

The standard treatment for patients with ER+ HER2- breast cancer is surgery to remove the tumor, which is then genetically tested to determine if chemotherapy or a combination of chemotherapy and radiation should follow. After this initial course of treatment, patients often begin taking an antiestrogen medication to suppress the cancer and prevent spread for up to five years.  

The medications function by lowering the body’s estrogen levels to starve the cancer cells of the fuel needed to grow. This therapeutic approach is extremely effective, but it comes with side effects. Lowering the estrogen level can instigate menopausal symptoms or aggravate symptoms including insomnia, hot flashes, joint stiffness and vaginal dryness.

Despite the benefit, up to 40% of patients experience a distant recurrence of cancer five years after beginning the antiestrogen therapy. Researchers believe a small subset of women with ER+ HER2- breast cancer develop a mutation in the cancer estrogen receptor that produces an escape hatch, allowing the cancer to bypass the standard antiestrogen therapies and spread throughout the body.

What is the EMBER-4 clinical trial?

Imlunestrant behaves differently than the standard therapy. Rather than lowering the concentration of estrogen in the body, it focuses on degrading the estrogen receptors on the surface of breast cancer cells. According to Dr. Harnden, this new medicine is also believed to potentially block the escape hatch available with the standard antiestrogen therapy. Because imlunestrant does not affect the estrogen levels in a woman’s body, it is likely to produce fewer side effects.

Based on earlier clinical trials focused on breast cancer that has spread, imlunestrant has been shown to be extremely effective. Participants have been able to tolerate the medication, and it does not appear to pose significant health risks.

The five-year EMBER-4 clinical trial began in October 2022 to compare imlunestrant to the standard antiestrogen therapy. The trial aims to enroll 6,000 participants in the open-label study. Participants are randomized in equal numbers in either the imlunestrant group or the standard antiestrogen therapy (tamoxifen or aromatase inhibitor) group. Inova Schar Cancer has been highly successful at bringing participants into the clinical trial.

“In world of research, clinical trials are slow to [recruit participants],” said Dr. Harnden. “We have enrolled over 20 patients to the study at our location. It is not only the highest accruing trial in the breast cancer program but a top trial for the cancer center in general.”

Who is eligible for the EMBER-4 clinical trial?

The trial is recruiting women with early-stage ER+ HER2- breast cancer that has not spread to other parts of the body but shows a clinically higher risk for potential recurrence or spread to other organs. Potential participants should have been using the standard antiestrogen therapy for at least two years but not longer than five years. Men who meet these criteria are also eligible to enroll in the clinical trial.

The trial’s primary goal is to compare invasive disease-free survival (excluding second nonbreast primary invasive cancers) between the two drug therapy groups. The second goal of the trial is to evaluate distant relapse-free survival, overall survival and invasive disease-free survival including secondary nonbreast primary invasive cancers, safety with pharmacokinetic exposures and patient-reported outcomes.

How can I learn more?

Inova Schar Cancer is currently recruiting ER+ HER2- breast cancer survivors who meet the criteria for this study. Interested people should call the new patient number 571-472-0635 or email the breast cancer clinical research nurse, Joshelynn Asis.