An estimated 80 percent of breast cancers are estrogen receptor positive and 65 percent progesterone receptor positive. For these, the most effective and targeted therapy is hormonal (or endocrine) therapy, which works by cutting the reserve of hormones that the tumor feeds on to grow, or by preventing their link with the receptors. Since the 1990s, endocrine therapy has been shown to be effective in improving and lengthening disease-free survival time when administered for 5 years following surgery. Despite the general effectiveness, however, some cancers can become resistant to endocrine drugs over time. Even in the presence of a mutation in an ESR1 estrogen receptor gene, hormonal drugs have so far proved ineffective. However, according to new research, published in Science Translational Medicine and conducted by Genentech’s Discovery Oncology Department (in the US), the second-generation drug giredestrant may be able to overcome resistance to hormonal therapies.
Breast cancer: faster therapy thanks to a new formulation
by Letizia Gabaglio
The first results
For some time, research in the field of “hormonal” breast cancer has been focusing on a new generation of Serd drugs (selective estrogen receptor degraders), including giredestrant. By studying the mammary glands of mice that had a mutation in the ESR1 gene, the researchers noted that the mutation promoted a hypersensitivity of the cells to progesterone, which particularly stimulated their growth. However, if these mice were given the drug giredestrant, growth stopped.
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Currently, the drug is being tested (in a Phase 1 clinical trial) in a group of metastatic patients with estrogen receptor positive cancer. In one of them – the researchers reported – the molecule showed signs of a partial response in reducing receptor activity and stopping tumor growth. Results that open a possible new path, of course, but which will have to be confirmed in much larger studies.