Although survival rates for breast cancer are relatively high, the fact that breast cancer is not a single disease but comprises as many as 10 different subtypes with distinct characteristics means that each subtype requires a specific treatment approach. Nancy Chan, MD, clinical research director for breast cancer at NYU Langone Health’s Perlmutter Cancer Center, leads a recently launched clinical trial called I-SPY 2 that offers patients with different subtypes of breast cancer an opportunity to take advantage of novel therapeutics.

“The goal of I-SPY 2 is to use genomic assays and novel therapeutics to match patients in a personalized treatment approach to enhance standard treatment in breast cancer,” said Dr. Chan, who is also a medical oncologist at the Breast Cancer Center. “The treatment is guided by the genomic assay MammaPrint, which provides information that we normally would not have to characterize the tumor.”

I-SPY 2 is a “platform” trial, meaning it uses a master protocol that provides a regulatory framework to study multiple treatments in the same study. People with breast cancer tumors at least 2.5 centimeters wide are eligible to enroll.

The standard of care for people with tumors that are 2.5 centimeters or larger is sometimes neoadjuvant chemotherapy, or treatment before surgery. In most cases, the standard treatment is chemotherapy alone. However, chemotherapy is combined with HER2-directed therapy for people with HER2-positive tumors, and people with triple-negative breast cancer are often treated with a combination of chemotherapy and immunotherapy.

I-SPY 2 aims to introduce novel agents early in the neoadjuvant setting that can enhance the standard chemotherapy “backbone”—the foundational chemotherapy regimen that forms the basis of a treatment plan.

Because every breast cancer is unique, even within subtypes, the study uses genomic assays of the biopsied tumor to categorize which treatments would work in a particular patient. Genomic information can help predict whether a particular cancer will respond to immunotherapy or DNA-damaging agents or something else entirely.

MRI scans are done at three points in the first 12 weeks of treatment to determine functional tumor volume, a calculation that can predict the likelihood of having a complete response. Patients who are predicted to have a complete response can de-escalate, or decrease, the dosage of chemotherapy.

“This trial is unique in that the tools we are using, from the genomic assays to the predictive MRI scans, are not part of mainstream treatments for breast cancer,” said Dr. Chan, who is also associate professor in the Department of Medicine at NYU Grossman School of Medicine. “We hope that the results of this study will help move these tools into standard practice.”

Trial Tests Drug Combinations for Metastatic Breast Cancer

Like all subtypes, breast cancers with receptors for the hormones estrogen or progesterone, known as hormone receptor–positive breast cancers, require personalized treatment. Dr. Chan leads another recently launched breast cancer study called ELEVATE.

A phase 1b/2 open-label trial, ELEVATE is an umbrella study to test combinations of the oral selective estrogen receptor degrader (SERD) elacestrant with different targeted therapies already approved by the U.S. Food and Drug Administration (FDA). The trial is specifically for patients with hormone-positive breast cancer who have already progressed on first- or second-line treatment.

Elacestrant is the first FDA-approved oral SERD. The only other FDA-approved SERD, fulvestrant, is a monthly injection that requires more frequent visits. On the ELEVATE trial, elacestrant can be given to patients who are receiving any of the three CDK 4/6 inhibitors (abemaciclib, ribociclib, and palbociclib); patients with PIK3CA mutations who are taking alpelisib; and patients taking everolimus, which acts on the mTOR pathway.

“The only other FDA-approved SERD, fulvestrant, is a painful monthly injection that is logistically harder for patients to receive,” Dr. Chan said. “Based on the results from the earlier EMERALD trial, we think that elacestrant, in combination with other drugs for metastatic breast cancer, will offer patients another option for treatment.”