Breast Cancer Targeted Treatments are Tested

Although breast cancer survival rates are very high, the fact that the illness is divided into as many as ten separate subtypes with distinct characteristics means that each subtype requires a unique therapeutic approach. Nancy Chan, MD, clinical research director for breast cancer at NYU Langone Health’s Perlmutter Cancer Center, leads I-SPY 2, a recently started clinical trial that allows patients with various subtypes of breast cancer to benefit from newer treatments.

“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,” Dr. Chan, also a medical oncologist at the Breast Cancer Center, explained. “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, which means it employs a master protocol that serves as a regulatory framework for studying various therapies concurrently. People with breast cancer tumors measuring at least 2.5 cm in diameter are eligible to participate.

For persons with tumors of 2.5 cm or greater, neoadjuvant chemotherapy, or treatment before surgery, is sometimes used. Chemotherapy alone is the standard treatment in most situations. For persons with HER2-positive tumors, chemotherapy is commonly combined with HER2-directed therapy, while people with triple-negative breast cancer are often treated with a combination of chemotherapy and immunotherapy.

The goal of I-SPY 2 is to introduce innovative medicines early in the neoadjuvant setting that can improve the traditional chemotherapy “backbone”—the basic chemotherapy regimen that serves as the base of a treatment plan.

Because each breast cancer is distinct, even within subtypes, the study employs genomic analyses of biopsied tumors to determine which treatments would be effective in a given patient. Genomic data can help forecast whether a certain tumour will respond to immunotherapy, DNA-damaging drugs, or something totally else.

MRI scans are performed three times during the first 12 weeks of treatment to measure functional tumor volume, which can predict the likelihood of a complete response. Patients who are expected to have a complete response can have their chemotherapy dose de-escalated, or reduced.

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

Drug Combination Trial for Metastatic Breast Cancer
Breast tumors with estrogen or progesterone receptors, known as hormone receptor-positive breast cancers, require tailored treatment just like any other subtype. Dr. Chan is the principal investigator of the ELEVATE breast cancer trial, which was recently launched.

ELEVATE, a phase 1b/2 open-label trial, is an umbrella research designed to investigate combinations of the oral selective estrogen receptor degrader (SERD) elacestrant with multiple FDA-approved targeted treatments. The trial is only for patients with hormone-positive breast cancer who have progressed on first- or second-line therapy.

Elacestrant was the first oral SERD authorized by the FDA. Fulvestrant, the only other FDA-approved SERD, is a monthly injection that necessitates more regular visits. In the ELEVATE trial, elacestrant can be given to patients getting any of the three CDK 4/6 inhibitors (abemaciclib, ribociclib, or palbociclib); patients with PIK3CA mutations receiving alpelisib; and patients receiving 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,” said Dr. Chan. “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.”

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