Early-stage hormone-receptor (HR)-positive, HER2-negative breast cancer accounts for 70 percent of early breast cancer diagnoses.

For more than two decades, treatment for breast cancer has involved surgery followed by endocrine therapies such as aromatase inhibitors and tamoxifen for five years.

Overall survival rates in patients who receive standard endocrine therapies are high, however up to 33 percent of patients have a recurrence of their disease.

The new drugs shut down estrogen signaling pathways more precisely than older endocrine therapies, as a result, the estrogen receptor breaks down.

Because disease recurrence poses a challenge for patients with early-stage HR-positive breast cancers, more effective endocrine therapies are needed, Aditya Bardia, the principal investigator, told TheDoctor. “This has the potential to reshape clinical practice for a large proportion of patients with breast cancer.”

The new drug, one of a newer class of drugs called oral selective estrogen receptor antagonists and degraders, are designed to block the signaling from estrogen receptors that HR-positive tumors need to grow. These drugs shut down these signaling pathways more precisely than older endocrine therapies, according to the findings of the international study led by UCLA researchers. As a result, the estrogen receptor breaks down.

The hope is that the new drugs can extend disease-free survival time for early-stage HR-positive, HER2-negative breast cancer patients beyond that offered by older endocrine therapies and reduce the risk of cancer metastases to other organs.

The drug in the UCLA study, giredestrant, is currently in phase 3 trials in combination with currently approved treatments for breast cancer.

The researchers enrolled 4,170 patients with early-stage HR-positive, HER2-negative breast cancer in the trial. Participants were about 54 years old and 59 percent of them were postmenopausal.

Patients treated with giredestrant were 30 percent less likely than those given endocrine therapies to have a recurrence or progression of invasive disease after a follow-up period of about 32 months.

About half of the participants received 30 mg of giredestrant for up to five years and the other half, the control group, received endocrine therapies.Patients treated with giredestrant were 30 percent less likely than those given endocrine therapies to have a recurrence or progression of invasive disease after a follow-up period of about 32 months.

Women treated with giredestrant also had 31 percent fewer metastases to other organs.

Many patients have difficulty tolerating endocrine inhibitors, which makes it difficult for them to stick with treatment, said Bardia, a professor of medicine at the David Geffen School of Medicine at UCLA and the director of translational research integration at the UCLA Health Jonsson Comprehensive Cancer Center. Both the giredestrant and control groups experienced similar side effects, such as hot flashes, joint aches and headaches, in the current study; but about five percent of participants taking giredestrant discontinued treatment, compared to about eight percent of those in the control group.

The findings of the current study were presented at the San Antonio Breast Cancer Symposium; it has not yet been published in a peer-reviewed journal.