Benefits of selectivity

Postmenopausal women with estrogen receptor (ER)-positive breast cancers are initially treated with drugs that block the production of estrogen, whose binding to the ER drives such cancers. When the tumors become resistant to these therapies, they’re treated with more potent drugs—such as fulvestrant—that bind to and inhibit ER activity. ER inhibitors, however, have side effects that mimic the unpleasant consequences of menopause. A study led by Ludwig Chicago Co-director Geof Greene examined whether the selective ER inhibitor lasofoxifene might also be used to treat estrogen resistant breast cancers in mouse models of human tumors driven by two common ER mutations, Y537S and D538G ERα. Lasofoxifene , which has anti-estrogenic effects in some tissues and pro-estrogenic effects in others, improves bone density in postmenopausal women and significantly reduces the incidence of ER-positive breast cancer. But its therapeutic utility hasn’t yet been determined. Geof and his colleagues reported in Breast Cancer Research in May that lasofoxifene was more effective than fulvestrant—when either drug was used alone or in combination with a common chemotherapy—in inhibiting both primary tumor growth and metastasis in the cancer models. Because lasofoxifene is relatively less toxic, it could potentially improve the treatment of progressive breast cancer. Clinical trials are underway to evaluate lasofoxifene in women with endocrine therapy resistant, ER+ metastatic breast cancer.

This article appeared in the August 2021 issue of Ludwig Link. Click here to download a PDF (2MB).


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