Treatment options have expanded in recent years for people diagnosed with early-stage breast cancer that is hormone receptor-positive (HR+), HER2-negative, and at high risk of coming back (recurring). Today, FDA-approved options for these patients include adding a type of targeted medicine called a CDK4/6 inhibitor to hormone therapy (also called endocrine therapy) after surgery.

A CDK4/6 inhibitor is a medicine (in pill form) that blocks specific proteins, called CDK4 and CDK6, from helping cancer cells to grow and divide. Hormone therapy stops natural hormones like estrogen from fueling the growth of HR+ breast cancer. Recent clinical trials have shown that when patients take these drugs together, this combination can further lower the risk that cancer will return compared to hormone therapy alone.

But this major advance has created a new treatment question: When patients receive hormone therapy plus a CDK4/6 inhibitor, does chemotherapy provide additional benefit? The answer is not known for one important group of patients.

This group consists of patients who may receive differing information about their risk of recurrence. Their cancer has features associated with a higher risk of recurrence, such as larger tumor size or cancer found in nearby lymph nodes. At the same time, genomic testing of their tumor shows a lower risk based on the cancer’s biology. Today, chemotherapy is still recommended for this group of patients.

Previous studies of CDK4/6 inhibitors could not answer whether chemotherapy provides additional benefit because most participants in those studies had already received chemotherapy before joining the trials. As a result, researchers could not find out whether chemotherapy itself was providing additional benefit.

Can chemotherapy be omitted for these patients? The EA1242/RxFINE-Low research study is designed to provide evidence to answer this question.

Because eligibility is based in part on the Oncotype DX Breast Recurrence Score®, the study could also provide evidence about whether genomic risk can help guide chemotherapy decisions for patients deemed at high risk of recurrence based on tumor size and lymph node involvement. The Recurrence Score analyzes genes in a patient's tumor to help estimate the risk that the cancer will return (on a scale of 0-100).

RxFINE-Low is a phase 3 clinical trial that plans to enroll about 2,000 postmenopausal women and men with breast cancer that is HR+—specifically estrogen receptor-positive (ER+), which is a subtype of HR+ breast cancer—and HER2-negative breast cancer, with a low Oncotype DX Breast Recurrence Score® (0-25). To be eligible, they must have completed surgery and meet the study criteria for high risk based on tumor size and lymph node involvement.

Participants will be randomly assigned by a computer to receive either chemotherapy or no chemotherapy. Afterward, all participants will receive hormone therapy with an aromatase inhibitor (anastrozole, exemestane, or letrozole) combined with ribociclib, an FDA-approved CDK4/6 inhibitor.

If the study shows that patients who do not receive chemotherapy have outcomes similar to those who do receive it, the findings would suggest that chemotherapy may be omitted in patients with a low Recurrence Score. This could spare these patients from the short- and long-term side effects of chemotherapy. If the study finds that chemotherapy provides additional benefit, it will remain an important part of treatment alongside hormone therapy and a CDK4/6 inhibitor.

Also, the trial results could provide evidence to help inform future insurance coverage decisions. Currently, there is not enough evidence to support using genomic testing to guide chemotherapy decisions for patients at high risk of recurrence based on tumor size and lymph node involvement. As a result, some insurance plans may not cover this testing for these patients.

Learn more about EA1242/RxFINE-Low at ecog-acrin.org.

For more information about breast cancer or to find resources and support, visit Living Beyond Breast Cancer, Touch, The Black Breast Cancer Alliance, or Young Survival Coalition.