Lasofoxifene Explored in ESR1-Mutated ER+/HER2- Breast Cancer

Rachel Narozniak
Published: Thursday, Sep 12, 2019
Dr Matthew Goetz

Matthew Goetz, MD
Investigators are exploring whether lasofoxifene can stop disease progression in women with advanced or metastatic estrogen receptor (ER)–positive, HER2-negative breast cancer with an ESR1 mutation in the multicenter phase II ELAINE trial (NCT03781063).

“However, like any other agent, disease will eventually progress on CDK4/6 inhibitors,” Goetz said. “[Resistance] is a major clinical problem. We need new approaches to treat these women.”

Figure. Lasofoxifene Versus Fulvestrant Phase II ELAINE Trial (Click to Enlarge)

Lasofoxifene is a selective ER modulator (SERM) that binds to the ER with high affinity to inhibit estrogen-dependent cancer cell proliferation in ER-expressing cancers.4 Like lasofoxifene, tamoxifen is a SERM that binds to the ER to promote antiestrogenic activity. The nonsteroidal compound is a recommended treatment option for both pre- and postmenopausal women with breast cancer and is most commonly used in the adjuvant setting in patients with early-stage disease to reduce the risk of recurrence. The National Comprehensive Cancer Network guidelines recommend 5 to 10 years of treatment with tamoxifen.5

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