Giredestrant Reduces Recurrence Risk More Than Tamoxifen, Aromatase Inhibitors

Taking giredestrant after surgery to remove early-stage hormone receptor-positive HER2-negative breast cancer seems to lower the risk of the cancer coming back (called recurrence) more than taking tamoxifen or an aromatase inhibitor. Giredestrant is a new oral selective estrogen receptor downregulator (SERD), a type of hormonal therapy.

The research was presented at the 2025 San Antonio Breast Cancer Symposium.

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  People who took giredestrant were 30% less like to have any type of recurrence — cancer coming back in the breast area or in any part of the body — than people who took tamoxifen or one of the aromatase inhibitors: Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), or Femara (chemical name: letrozole).

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  People who took giredestrant were 31% less likely to have distant or metastatic recurrence — cancer coming back in a part of the body away from the breast — than people who took tamoxifen or an aromatase inhibitor.

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  The side effects of giredestrant were similar to those of tamoxifen and the aromatase inhibitors – hot flashes and joint and muscle pain – but they appeared to be less severe. About 5% of people taking giredestrant stopped treatment because of side effects compared to about 8% of people taking an aromatase inhibitor or tamoxifen.

Longer follow-up of the study is needed, but if the results are confirmed, the findings could mean the first major change in treatment after surgery for early-stage hormone receptor-positive breast cancer in more than 25 years.

While giredestrant isn’t yet approved by the U.S. Food and Drug Administration (FDA), Genentech, the company that makes it, is expected to apply for approval very soon.

After surgery, many people diagnosed with early-stage hormone receptor-positive HER2-negative breast cancer take hormonal therapy, usually tamoxifen or an aromatase inhibitor, for five to 10 years to lower the risk of recurrence. Although survival rates are high with this treatment, up to 33% of people have the cancer come back. Research also shows that many people struggle with the side effects of tamoxifen and the aromatase inhibitors; studies suggest that up to 50% of people either don’t start their prescribed medicine or stop taking it early.

“In early [estrogen receptor]-positive breast cancer, challenges with disease recurrence and treatment adherence mean there is an urgent need for more effective, tolerable endocrine therapies,” Aditya Bardia, MD, MPH, professor of medicine at the David Geffen School of Medicine at UCLA, said during a media briefing on the results. Bardia is also director of translational research integration at the UCLA Health Jonsson Comprehensive Cancer Center.

Bardia and his colleagues studied whether giredestrant could be a better option than currently used hormonal therapies.

The lidERA study included 4,170 people diagnosed with stage I to stage III hormone receptor-positive HER2-negative node-positive breast cancer. Half the people were older than 54 and half were younger. About 60% were post-menopausal.

After surgery, the people were randomly assigned to one of two treatments for five years:

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  2,084 people took giredestrant

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  2,086 people took tamoxifen or one of the aromatase inhibitors, whichever their doctor recommended; if people had unacceptable side effects, they could switch to a different aromatase inhibitor

Three years after completing the five years of treatment, 92.4% of the people who took giredestrant were alive with no recurrence compared to 89.6% of people who took tamoxifen or an aromatase inhibitor. This difference was statistically significant, which means that it was likely due to the difference in treatments and not just because of chance. 

This benefit was consistent regardless of menopausal status, cancer stage, and whether or not a person had received chemotherapy before surgery.

Information on overall survival — how long people live whether or not the cancer comes back — wasn’t ready to be analyzed. But Bardia said there was a trend for better survival with giredestrant.

The most common treatment-related side effects in both treatment groups were mild and included joint pain, hot flashes, and headache. Less than 2% of the people in either treatment group had serious side effects, such as high blood pressure and joint pain.

Bradycardia, or a slow heart rate, is a known side effect of oral SERDs. About 11% of people who took giredestrant had bradycardia compared to about 3% of people who took tamoxifen or an aromatase inhibitor. But most of these cases were grade 1, caused no symptoms, and didn’t require people to pause or stop treatment.

“The frequency of side effects were similar, including the frequency of [joint pain], with giredestrant and the standard of care endocrine therapy,” Bardia said during an episode of The Breastcancer.org Podcast, “but treatment discontinuation because of [joint pain] was lower with giredestrant compared to the standard of care endocrine therapy.”